subject:(lentivirus)

University of Texas Southwestern Medical Center

1. Ellis, Brian Lee. Improving Viral Vectors for Gene Targeting in Gene Therapy.

Degree: 2011, University of Texas Southwestern Medical Center

► Over 10,000 monogenic diseases in the world affect one out of every hundred live births (WHO). Gene targeting is a term that is used describe… (more)

▼ Over 10,000 monogenic diseases in the world affect one out of every hundred live births (WHO). Gene targeting is a term that is used describe the manipulation of genetic material, either by adding a gene in a specific locus, creating a mutation at a specific locus, or correcting a gene at a specific locus. Here, unless otherwise noted, we will use the term to describe the correction of a gene with a homologous piece of donor genetic material whereby a mutant gene that causes monogenic disease is essentially replaced by a wild type copy through homologous recombination. Thus, gene targeting is inherently safer than classic gene therapy, where a gene is randomly introduced into the genome and can cause insertional mutagenesis. Although the rates of homologous recombination are low when simply delivering a donor substrate (1 in a million), creating a deoxyribonucleic acid (DNA) double-stranded break in or around the gene of interest using a nuclease, increases the rate of gene targeting 30,000-50,000 fold. The delivery of the nuclease and donor substrate to these cells is one of the major hurdles in achieving this type of therapy. However, for classic gene therapy there have already been many clinical trials using viral vehicles for gene delivery. One problem with using a virus for gene therapy is the low titer associated with some types of virus, in particular, lentivirus. In the first part of this dissertation, this problem is addressed by showing that the addition of caffeine during viral production can increase titer up to 8-fold. Besides lentivirus, other viruses, like Adeno-associated virus (AAV) have been used in clinical trials. There are nine AAV serotypes, but the most-well characterized is AAV2. Because there are situations where AAV is to be used in cells that cannot be transduced with AAV2, it is essential to know which serotype best infects the desired cell type. The second part of the dissertation describes a comprehensive survey of the ability of AAV1-9 and one engineered serotype to transduce primary and immortalized cells from human, mouse, hamster, and monkey origin. Overall, the results show that AAV1 and AAV6 transduce the most cell types at the highest efficiencies. Though gene targeting has been achieved using the homing endonuclease I-Sce in AAV2, targeting has never been achieved using two zinc-finger nucleases (ZFNs) in any AAV serotype. This is significant because the recognition site for I-Sce is not found in the human genome, while ZFNs are designed to specifically bind in or around a gene of interest. Based on the results from the AAV survey and the advantage of ZFNs, we created an AAV6 virus that carried the genetic information for both ZFNs and donor substrate for gene targeting in cells containing a GFP gene targeting system. We also created an AAV6 virus that carried the donor substrate alone. The third part of this dissertation reveals that dual infection at the optimal multiplicities of infection for both AAV viruses can achieve targeting efficiencies of ~3%, which is… Advisors/Committee Members: Porteus, Matthew H..

Subjects/Keywords: Gene Targeting; Gene Therapy; Lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ellis, B. L. (2011). Improving Viral Vectors for Gene Targeting in Gene Therapy. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/837

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ellis, Brian Lee. “Improving Viral Vectors for Gene Targeting in Gene Therapy.” 2011. Thesis, University of Texas Southwestern Medical Center. Accessed March 06, 2021. http://hdl.handle.net/2152.5/837.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ellis, Brian Lee. “Improving Viral Vectors for Gene Targeting in Gene Therapy.” 2011. Web. 06 Mar 2021.

Vancouver:

Ellis BL. Improving Viral Vectors for Gene Targeting in Gene Therapy. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2152.5/837.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ellis BL. Improving Viral Vectors for Gene Targeting in Gene Therapy. [Thesis]. University of Texas Southwestern Medical Center; 2011. Available from: http://hdl.handle.net/2152.5/837

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

2. Kremer, Karlea Lee. Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/63153

► Gene therapy potentially holds the key for the treatment and cure of many genetic diseases, including cystic fibrosis. A number of delivery methods have been… (more)

▼ Gene therapy potentially holds the key for the treatment and cure of many genetic diseases, including cystic fibrosis. A number of delivery methods have been developed for the integration of a functional gene into the host genome, one of which is the use of a HIV-1 derived lentivirus, as is used in this thesis. However, a large number of issues need to be addressed before an effective gene therapy protocol can be developed, and some of these are described further in this thesis. One such issue is that the response initiated by cells to the gene transfer vector need to be addressed, as organelles such as the proteasome and lysosome that break down foreign peptides and proteins may be involved in the degradation of our gene transfer vector, ultimately limiting the amount of gene transfer vector that is able to successfully integrate into the genome. Therefore, the potential use of proteasome and lysosome inhibitors for facilitating higher levels of gene transduction in vivo was investigated. As this project uses a HIV-1 derived lentivirus for gene transfer, the use of an inhibitor of the IN1/PML innate antiretroviral response (Leptomycin B) was also assessed, again with the aim of increasing the efficiency, and hence level, of gene transfer obtained. Using a robust animal model of disease is essential for testing lentivirus constructs containing the therapeutic gene and analysing phenotypic changes in disease. A mouse model of cystic fibrosis without gastrointestinal disease was bred to obtain a robust colony of mice that efficiently produce affected mice (CFTR knockout). Visual analysis of therapeutic gene transfer in cystic fibrosis is often difficult due to the lack of antibodies available. Short DNA molecules that adopt a specific 3-D shape known as aptamers hold much potential as agents that can be developed to bind to the CFTR gene product. These can then be labelled and used in the same way as antibodies to probe tissues excised from animals treated with the therapeutic CFTR gene. Essential to gene therapy is the development of methods for the consistent determination of lentivirus titre. As the production of lentivirus becomes more sophisticated with the use of multiple transgenes in a single virus preparation, the need for multiple assays to determine the titres of each individual virus component are required. Real time PCR assays were developed for each individual transgene for titre determination. A real time PCR assay for use with CHOK-1 cells was also developed for comparison of real time PCR titre of a LacZ virus to the titre obtained using the traditional LacZ titre achieved via a staining assay in CHOK-1 cells. The use of a standard real time PCR assay for the determination of titre for all viruses- containing any transgene is essential to allow comparison by titre. Determination of the level of gene expression required to achieve a therapeutic outcome in a cystic fibrosis mouse model is an important factor to consider, as high level expression in all cells may not achieve the best outcomes, and low… Advisors/Committee Members: Anson, Donald Stewart (advisor), Parsons, David Webb (advisor), School of Paediatrics and Reproductive Health (school).

Subjects/Keywords: cystic fibrosis; gene therapy; lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kremer, K. L. (2010). Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/63153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kremer, Karlea Lee. “Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery.” 2010. Thesis, University of Adelaide. Accessed March 06, 2021. http://hdl.handle.net/2440/63153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kremer, Karlea Lee. “Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery.” 2010. Web. 06 Mar 2021.

Vancouver:

Kremer KL. Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2440/63153.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kremer KL. Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/63153

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Victoria University of Wellington

3. Upton, Jevon. Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes.

Degree: 2020, Victoria University of Wellington

URL: http://hdl.handle.net/10063/8944

► Developing transgenic livestock has become popular in recent years after advances in the field of genetic editing. Cattle are one of the main exports in… (more)

▼ Developing transgenic livestock has become popular in recent years after advances in the field of genetic editing. Cattle are one of the main exports in New Zealand and are a prime target for new genetic editing tools. Applications of genetic editing in cattle can extend to increases in production, and elimination of disease genes. Due to its ease of use, CRISPR/Cas9 has become one of the most popular methods of editing genes, hence this was employed in the research. Cattle embryos in culture are very sensitive to environmental changes and for this reason, a delivery vector is necessary to deliver the genetic material as traditional transfection methods cause high rates of embryo death. The zona pellucida, a glycoprotein coat surrounding the embryo, acts as a protective agent against viral vectors, and needed to be considered in the research. This research aimed to create a novel, high titer lentivirus particle capable of transducing bovine embryos, and causing subsequent genetic modification by integration of CRISPR/Cas9 into the genome. Using fluorescent reporters, viral transduction was monitored. The research found that after optimizing transfection protocols, high-titer lentiviral particles can be produced and can infect bovine embryos. Zona pellucida removal experiments revealed over-digestion in early stage embryos, however, this was not observed in compact morulas. Removing the zona allowed for successful transduction of bovine embryos, resulting in transgenic cells expressing eGFP. While CRISPR/Cas9 experiments were in preliminary stages, these indicated eGFP knock-out in certain eGFP-HEK293T cells. Though challenges were encountered throughout the research process, solutions were explored, and it was shown that transgenic bovine embryos using lentiviral gene delivery can be produced. This indicates the high likelihood that CRISPR/Cas9 systems can be delivered this way, inducing targeted genetic modification. Advisors/Committee Members: Pfeffer, Peter.

Subjects/Keywords: CRISPR/Cas9; Bovine Embryology; Lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Upton, J. (2020). Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes. (Masters Thesis). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/8944

Chicago Manual of Style (16^th Edition):

Upton, Jevon. “Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes.” 2020. Masters Thesis, Victoria University of Wellington. Accessed March 06, 2021. http://hdl.handle.net/10063/8944.

MLA Handbook (7^th Edition):

Upton, Jevon. “Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes.” 2020. Web. 06 Mar 2021.

Vancouver:

Upton J. Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes. [Internet] [Masters thesis]. Victoria University of Wellington; 2020. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10063/8944.

Council of Science Editors:

Upton J. Using Lentivirus and CRISPR to Modify Cattle Embryonic Genes. [Masters Thesis]. Victoria University of Wellington; 2020. Available from: http://hdl.handle.net/10063/8944

Victoria University of Wellington

4. Ni, Shicheng. Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis.

Degree: 2020, Victoria University of Wellington

URL: http://hdl.handle.net/10063/8989

► In recent times, cattle embryology has been under the spotlight of investigation due to its apparent economic values. This is especially relevant in the case… (more)

▼ In recent times, cattle embryology has been under the spotlight of investigation due to its apparent economic values. This is especially relevant in the case of New Zealand, owing to its high percentage of livestock export. Specifically, the period of peri-implantation development has been of particular relevance. During this stage, the developing zygote will establish 3 key lineages – epiblast, hypoblast and trophoblast. Previous studies have elucidated that a significant number of embryos die prior to implantation, therefore highlighting the importance of correctly establishing these 3 lineages to overall embryonic survival. However, while embryological stages of the preimplantation embryo have been extensively studied in their eutherian cousin, mice, the molecular regulation of that of cattle remains much less addressed. Whereas the regulation of bovine embryo development is orchestrated by many transcriptional regulators, or genetic regulatory networks (GNP), we aimed to focus our studies on 2 key transcriptional regulators, GATA4 and GATA6. During early embryogenesis, both these transcriptional factors are known molecular regulators that drive the establishment of the hypoblast lineage in mice. By and large, while their respective expression has been documented in cattle embryos, functional studies towards these markers have not yet been performed. Latest advances in molecular biology have given us novel methods to study the mechanism of bovine embryogenesis. To this end, the continuing perfection of CRISPR technologies in the last decade - in particular its delivery through lentiviral vectors, has established an ability to generate stable, targeted knock-out mutants. Therefore, it is aimed in this thesis to design and test lentiviral particles that induce knock-out mutants of GATA4 and GATAT6, to test their efficacy in primary cell cultures (bovine cumulus cells) and to functionally analyse the effect of GATA4 and GATA6 knockdowns in early bovine embryos. Advisors/Committee Members: Pfeffer, Peter.

Subjects/Keywords: CRISPR; Bovine Embryology; Lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ni, S. (2020). Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis. (Masters Thesis). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/8989

Chicago Manual of Style (16^th Edition):

Ni, Shicheng. “Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis.” 2020. Masters Thesis, Victoria University of Wellington. Accessed March 06, 2021. http://hdl.handle.net/10063/8989.

MLA Handbook (7^th Edition):

Ni, Shicheng. “Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis.” 2020. Web. 06 Mar 2021.

Vancouver:

Ni S. Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis. [Internet] [Masters thesis]. Victoria University of Wellington; 2020. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10063/8989.

Council of Science Editors:

Ni S. Adapting CRISPR/Cas9 Lentivirus Technology for Functional Studies of GATA6 & GATA4 during Bovine Preimplantation Embryogenesis. [Masters Thesis]. Victoria University of Wellington; 2020. Available from: http://hdl.handle.net/10063/8989

University of Southern California

5. Froelich, Steven Michael. Engineering lentiviral vectors for gene delivery.

Degree: PhD, Chemical Engineering, 2011, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/459666/rec/2368

► The development of lentiviral vectors to deliver genes to specific cell types are useful tools because they have the ability to produce stable transduction, maintain… (more)

Subjects/Keywords: lentivirus; DC-SIGN; dendritic cell

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Froelich, S. M. (2011). Engineering lentiviral vectors for gene delivery. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/459666/rec/2368

Chicago Manual of Style (16^th Edition):

Froelich, Steven Michael. “Engineering lentiviral vectors for gene delivery.” 2011. Doctoral Dissertation, University of Southern California. Accessed March 06, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/459666/rec/2368.

MLA Handbook (7^th Edition):

Froelich, Steven Michael. “Engineering lentiviral vectors for gene delivery.” 2011. Web. 06 Mar 2021.

Vancouver:

Froelich SM. Engineering lentiviral vectors for gene delivery. [Internet] [Doctoral dissertation]. University of Southern California; 2011. [cited 2021 Mar 06]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/459666/rec/2368.

Council of Science Editors:

Froelich SM. Engineering lentiviral vectors for gene delivery. [Doctoral Dissertation]. University of Southern California; 2011. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/459666/rec/2368

University of Tasmania

6. Casey, NP. The Therapeutic potential of lentivector-delivered RNAi.

Degree: 2010, University of Tasmania

URL: https://eprints.utas.edu.au/10783/1/01_Casey_front.pdf ; https://eprints.utas.edu.au/10783/2/01_Casey_whole.pdf

► Many forms of leukaemia are caused by chromosomal translocations, which result in specific and characteristic genomic sequences. Where these sequences are unique to the leukaemic… (more)

▼ Many forms of leukaemia are caused by chromosomal translocations, which result in specific and characteristic genomic sequences. Where these sequences are unique to the leukaemic cells, they represent good candidates for targeting by sequencespecific techniques, such as RNA-Interference (RNAi). RNAi is a mechanism inherent in eukaryotic cells which silences target mRNAs based on homology to a dsRNA template. This template may be introduced artificially by a number of methods, and so this mechanism can be manipulated to regulate the expression of target genes. One of the most efficient methods of introducing RNAi templates is by expression of shorthairpin RNA (shRNA) cassettes from DNA plasmids or vectors. Lentiviral vectors are based on viruses that integrate into the DNA of the host cell, and are a highly efficient class of vectors for transducing and providing stable transgene expression in a range of cell types. They are particularly effective at tansducing haematopoietic cells, which have proven difficult to transduce by other methods. By fine-tuning the methods of vector production and transduction, a range of human leukaemic cells lines were able to be transduced with unprecedented efficiency in the present study. Lentiviral transduction was combined with rapid puromycin selection to generate a pure population of transduced cells with minimal expansion of the cell population. The strategy of expressing shRNAs from retroviral and lentiviral vectors combined with puromycin selection was used to target three well-characterised fusion genes; Bcr-Abl, PML/RARα and RUNX1/ETO, in three human leukaemic cell lines. In two of these, the shRNA was able to efficiently and effectively down-regulate the target mRNA, and inhibit the proliferation of the transduced leukaemic cells. In the third case, RUNX1/ETO, no effective shRNA design could be identified. Finally, concerns over the safety of integration targeting by current gene therapy vectors motivated an investigation of the activity of a novel integrase enzyme from the Ty3 retrotransposon found in yeast. In yeast cells, the integration-mediating enzyme of this retrotransposon has very specific targeting characteristcs, which, if retained in human cells, would provide a very safe gene therapy vector. It was found that this enzyme is indeed active in human cells, and therefore has potential in the context of human gene therapy.

Subjects/Keywords: lentivirus; vector; RNAi; shRNA; chrosomal-translocation; leukaemia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Casey, N. (2010). The Therapeutic potential of lentivector-delivered RNAi. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/10783/1/01_Casey_front.pdf ; https://eprints.utas.edu.au/10783/2/01_Casey_whole.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Casey, NP. “The Therapeutic potential of lentivector-delivered RNAi.” 2010. Thesis, University of Tasmania. Accessed March 06, 2021. https://eprints.utas.edu.au/10783/1/01_Casey_front.pdf ; https://eprints.utas.edu.au/10783/2/01_Casey_whole.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Casey, NP. “The Therapeutic potential of lentivector-delivered RNAi.” 2010. Web. 06 Mar 2021.

Vancouver:

Casey N. The Therapeutic potential of lentivector-delivered RNAi. [Internet] [Thesis]. University of Tasmania; 2010. [cited 2021 Mar 06]. Available from: https://eprints.utas.edu.au/10783/1/01_Casey_front.pdf ; https://eprints.utas.edu.au/10783/2/01_Casey_whole.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Casey N. The Therapeutic potential of lentivector-delivered RNAi. [Thesis]. University of Tasmania; 2010. Available from: https://eprints.utas.edu.au/10783/1/01_Casey_front.pdf ; https://eprints.utas.edu.au/10783/2/01_Casey_whole.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Purdue University

7. Nichols, Jamieson. Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus.

Degree: MS, Veterinary Clinical Science, 2015, Purdue University

URL: https://docs.lib.purdue.edu/open_access_theses/1157

► Feline immunodeficiency virus is an important lentiviral infection in cats. Infection is life-long and results in immune compromise, increased susceptibility to opportunistic infections and early… (more)

Subjects/Keywords: cats; feline immunodeficiency virus; FIV; lentivirus; retrovirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nichols, J. (2015). Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus. (Thesis). Purdue University. Retrieved from https://docs.lib.purdue.edu/open_access_theses/1157

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nichols, Jamieson. “Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus.” 2015. Thesis, Purdue University. Accessed March 06, 2021. https://docs.lib.purdue.edu/open_access_theses/1157.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nichols, Jamieson. “Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus.” 2015. Web. 06 Mar 2021.

Vancouver:

Nichols J. Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus. [Internet] [Thesis]. Purdue University; 2015. [cited 2021 Mar 06]. Available from: https://docs.lib.purdue.edu/open_access_theses/1157.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nichols J. Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus. [Thesis]. Purdue University; 2015. Available from: https://docs.lib.purdue.edu/open_access_theses/1157

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

8. Padmanabhan, Harshavardini. Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis.

Degree: 2019, University of Adelaide

URL: http://hdl.handle.net/2440/120704

► Lentiviral (LV) vectors show promise as a gene therapy vector for cystic fibrosis (CF). The cystic fibrosis airway gene therapy group (CFARG) based in Adelaide,… (more)

▼ Lentiviral (LV) vectors show promise as a gene therapy vector for cystic fibrosis (CF). The cystic fibrosis airway gene therapy group (CFARG) based in Adelaide, Australia have developed a HIV-1 based LV vector that demonstrated expression of the corrective CFTR gene up to 12 months in the airways of CF mice. Using their two-step airway conditioning and bolus gene vector delivery technique, the CFARG have shown effective transduction in the airways of animal models such as sheep and marmosets. As this vector approaches clinical realisation there is a need to translate the bolus delivery regimen of this vector to an aerosol form. Aerosolisation would enable non-invasive and easily repeatable vector delivery, which could be used in future clinical trials. This thesis examines the efficiency of different delivery devices for aerosolising the LV vector. Cell culture studies showed that LV vector aerosolised using a newly developed ultrasonic surface acoustic wave (SAW) nebuliser produced significantly lower levels of gene expression than bolus delivery. This led to examination of an intra-tracheal sprayer, the MADgic™ atomisation device, which demonstrated promising results on delivering the vector as a spray, in cell culture studies. However, use of this device in human clinical studies is invasive. Therefore, the efficacy of delivering LV vector as an aerosol through other nebulisers was investigated. A baseline in vivo study was designed to aerosolise the LV vector into the lungs of mechanically ventilated mice using an Aeroneb®Pro vibrating mesh nebuliser with a flexiVent™ small animal ventilator. This was the first study to compare the levels of gene expression produced by a HIV-based LV vector delivered either as an aerosol or as a bolus dose into mouse lungs. Lower levels of gene expression were obtained in the trachea of aerosol-treated animals compared to bolus-treated animals. However, the effect of LV aerosol delivery could not be determined in other conducting airways or the lung parenchyma, due to low power of the study produced by a substantial outlier producing a far larger than expected variability. The reason for the lowered gene expression observed in the trachea of mice treated with LV vector delivered as an aerosol through the Aeroneb®Pro-flexiVent™ ventilator apparatus was not conclusive. Further experiments investigated the cause of the low levels of gene expression observed in the baseline in vivo study. Bench studies with dye solution revealed that the physical dose volume that reached the tip of the endotracheal (ET) tube following delivery through the ventilator circuit was only 2% of the initial dose volume, which likely explained the low levels of gene expression in trachea of aerosol-treated animals. The delivery parameters were therefore optimised to increase the aerosol output available at the end of the delivery circuit. Subsequent cell culture studies examined the gene expression produced by the LV vector aerosolised with parameters used in the baseline in vivo study. The results… Advisors/Committee Members: Parsons, David (advisor), Donnelley, Martin (advisor), Cmielewski, Patricia (advisor), Adelaide Medical School (school).

Subjects/Keywords: Gene therapy; aerosols; lentivirus; cystic fibrosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Padmanabhan, H. (2019). Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/120704

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Padmanabhan, Harshavardini. “Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis.” 2019. Thesis, University of Adelaide. Accessed March 06, 2021. http://hdl.handle.net/2440/120704.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Padmanabhan, Harshavardini. “Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis.” 2019. Web. 06 Mar 2021.

Vancouver:

Padmanabhan H. Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis. [Internet] [Thesis]. University of Adelaide; 2019. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2440/120704.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Padmanabhan H. Development of lentiviral airway gene therapy aerosol delivery techniques for cystic fibrosis. [Thesis]. University of Adelaide; 2019. Available from: http://hdl.handle.net/2440/120704

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Colorado State University

9. Baker, Callie M. Development of ovine placental lactogen deficient pregnancies, The.

Degree: MS(M.S.), Biomedical Sciences, 2014, Colorado State University

URL: http://hdl.handle.net/10217/88500

► Intrauterine growth restriction (IUGR) results in significant fetal and neonatal mortalities and morbidities. Additionally, infants surviving IUGR experience increased incidence of heart disease, diabetes, hypertension… (more)

▼ Intrauterine growth restriction (IUGR) results in significant fetal and neonatal mortalities and morbidities. Additionally, infants surviving IUGR experience increased incidence of heart disease, diabetes, hypertension and stroke during adulthood. A major placental secretory product, placental lactogen (PL), is found at high levels in maternal and fetal circulation, and is significantly reduced in both human and sheep IUGR pregnancies. While the exact function of PL has not been defined for any species, it is thought to modulate the mobilization of maternal nutrients to the fetus. Recently, the development of lentiviral-mediated expression of short hairpin RNA (shRNA) within sheep conceptuses has provided a means of examining placental gene function in sheep. The objective of this research was to generate ovine PL (oPL) deficient sheep pregnancies using lentivirus targeting the degradation of oPL mRNA, in order to assess the function of PL during pregnancy. We hypothesize that oPL deficiency during pregnancy will lead to IUGR near term. To test our hypothesis a preliminary study was conducted to evaluate the in vivo efficacy of lentiviral-oPL targeting vectors in the sheep placenta at 55 days gestational age (dGA). Efficiency of oPLmRNA degradation was first measured in vitro using twelve promoter-targeting sequence combinations, tested in three cell lines overexpressing oPL. Two oPL target sequences (tg2 and tg6) were used, as either shRNA or shRNAmiR (microRNA mimic) sequences. Subsequently, three lentiviral constructs; hLL3.7 tg6 (human U6 promoter expressing oPL tg6 shRNA), hEF-1 tg2 (human elongation factor-1α promoter expressing oPL tg 2 shRNAmiR) and oPGK tg6 (ovine phosphoglycerate kinase-1 promoter expressing oPL tg 6 shRNAmiR), were selected to be tested in vivo. Day 9 blastocysts were harvested from naturally mated donor ewes, infected with one of the lentiviral constructs, and 2 to 3 blastocysts were surgically transferred to recipient ewes. At 55 dGA, uterine vein (UtV) blood and placental tissues were collected for analysis of oPL expression, and compared to naturally mated controls (NMC). Based on a 95% confidence interval created from UtV oPL concentrations in NMC pregnancies (n=4), 3 out of 4 hLL3.7 tg6 pregnancies, 3 out of 4 hEF tg2 pregnancies and 4 out of 4 oPGK tg6 pregnancies were classified as responder pregnancies. Compared to NMC pregnancies, UtV oPL concentrations were significantly reduced (P≤0.05) in responder pregnancies. While we hypothesized that oPL deficiency will result in IUGR near-term, at 55 dGA there were no differences in fetal weights. To test our overall hypothesis, we generated 8 hEF-1-SC (human elongation factor-1α promoter expressing scrambled control shRNAmiR), 9 hEF-1 tg2, 7 hEF-1 tg6 (human elongation factor-1α promoter expressing oPL tg6 shRNAmiR) and 9 hLL3.7 tg6 singleton pregnancies that were harvested at 135 dGA. Based on two standard deviations below the mean placental weight of the hEF-1 SC pregnancies, 2 out of 7 hEF-1 tg6 pregnancies and 6 out… Advisors/Committee Members: Anthony, Russell V. (advisor), Winger, Quinton A. (committee member), Curthoys, Norman (committee member).

Subjects/Keywords: ovine; pregnancy; placental lactogen; IUGR; lentivirus; placenta

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APA (6^th Edition):

Baker, C. M. (2014). Development of ovine placental lactogen deficient pregnancies, The. (Masters Thesis). Colorado State University. Retrieved from http://hdl.handle.net/10217/88500

Chicago Manual of Style (16^th Edition):

Baker, Callie M. “Development of ovine placental lactogen deficient pregnancies, The.” 2014. Masters Thesis, Colorado State University. Accessed March 06, 2021. http://hdl.handle.net/10217/88500.

MLA Handbook (7^th Edition):

Baker, Callie M. “Development of ovine placental lactogen deficient pregnancies, The.” 2014. Web. 06 Mar 2021.

Vancouver:

Baker CM. Development of ovine placental lactogen deficient pregnancies, The. [Internet] [Masters thesis]. Colorado State University; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10217/88500.

Council of Science Editors:

Baker CM. Development of ovine placental lactogen deficient pregnancies, The. [Masters Thesis]. Colorado State University; 2014. Available from: http://hdl.handle.net/10217/88500

California State University – Sacramento

10. Cicchetto, Andrew C. Genetically modified multipotent stromal cells for the treatment of osteoarthritis.

Degree: MA, Biological Science (Stem Cell, 2016, California State University – Sacramento

URL: http://hdl.handle.net/10211.3/171158

► Osteoarthritis (OA) is a degenerative joint disease estimated to affect 630 million people worldwide. OA is characterized by the progressive loss of articular cartilage, damage… (more)

▼ Osteoarthritis (OA) is a degenerative joint disease estimated to affect 630 million people worldwide. OA is characterized by the progressive loss of articular cartilage, damage to subchondral bone and chronic inflammation; unfortunately, there is no cure for OA. Human mesenchymal stem cells/multipotent stromal cells (MSCs) have been evaluated as a potential treatment, as these cells can contribute through differentiation into bone and cartilage, and act as trophic mediators to reduce inflammation and promote healing. The safety of MSC therapies has been widely demonstrated and currently, at least 13 clinical trials are testing the efficacy of MSCs to treat OA. We hypothesized here that the efficacy of MSC therapy can be enhanced using lentiviral vectors to overexpress key factors including interleukin-10 (IL-10), IL-1 receptor antagonist (IL- 1RA) or fibroblast growth factor-2 (FGF-2). Based on our experience on how to perform these modifications in a clinically-compliant manner, our primary goal was to functionally characterize these genetically modified MSC in vitro. Collectively, experiments performed in our lab: (1) show effective over-expression of the respective transgenes at the mRNA and protein levels; (2) address the number of viral insertions per cell; (3) demonstrate that over-expressing FGF-2 exhibit increased proliferation rates and reduced differentiation potential into both the osteogenic and adipogenic lineage. In contrast, over-expression of IL-1RA or IL-10 did not affect cell proliferation or differentiation potential. Importantly, MSCs over-expressing IL-10 reveal significant immune suppressive abilities in vitro, as proliferation of PHA-activated peripheral blood mononuclear cells (PBMCs) were strongly inhibited in a co-culture system. These results support the notion of a ???second generation of MSCs,??? using genetic modifications to enhance therapeutic efficacy, while maintaining an excellent safety profile. Treatment of naturally occurring OA in dogs is now underway using canine MSCs overexpressing homologous IL-10. These studies will help establish safety and generate a proof of concept for advancing to human trials. Advisors/Committee Members: Carter, Rosalee C..

Subjects/Keywords: Interleukin-10; Gene Therapy; Cell Therapy; Lentivirus

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APA (6^th Edition):

Cicchetto, A. C. (2016). Genetically modified multipotent stromal cells for the treatment of osteoarthritis. (Masters Thesis). California State University – Sacramento. Retrieved from http://hdl.handle.net/10211.3/171158

Chicago Manual of Style (16^th Edition):

Cicchetto, Andrew C. “Genetically modified multipotent stromal cells for the treatment of osteoarthritis.” 2016. Masters Thesis, California State University – Sacramento. Accessed March 06, 2021. http://hdl.handle.net/10211.3/171158.

MLA Handbook (7^th Edition):

Cicchetto, Andrew C. “Genetically modified multipotent stromal cells for the treatment of osteoarthritis.” 2016. Web. 06 Mar 2021.

Vancouver:

Cicchetto AC. Genetically modified multipotent stromal cells for the treatment of osteoarthritis. [Internet] [Masters thesis]. California State University – Sacramento; 2016. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10211.3/171158.

Council of Science Editors:

Cicchetto AC. Genetically modified multipotent stromal cells for the treatment of osteoarthritis. [Masters Thesis]. California State University – Sacramento; 2016. Available from: http://hdl.handle.net/10211.3/171158

University of Sydney

11. Li, Alisha Jean-King. Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction .

Degree: 2015, University of Sydney

URL: http://hdl.handle.net/2123/14308

► Adipocytes function as the major storage site for triacylglyerol (TAG) and have important roles as active endocrine cells. It is widely assumed that the endocrine… (more)

▼ Adipocytes function as the major storage site for triacylglyerol (TAG) and have important roles as active endocrine cells. It is widely assumed that the endocrine function of fat cells is determined by their size. As adipocytes increase in size, they tend to release more pro-inflammatory secretions leading to the recruitment of macrophages, setting up a vicious cycle of inflammation. The aim of this study was to genetically manipulate the size of fat cells in culture to determine the effect on inflammatory behaviour. The size of adipocytes may be manipulated in vitro by increasing TAG storage in 3T3-L1 cells. Acyl-coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) catalyses the final and only committed step of TAG synthesis. Therefore key strategies in this study were to achieve overexpression of DGAT1 in 3T3-L1 preadipocytes, assess the resulting phenotype following differentiation, and to examine the adipocyte response to inflammatory stimuli as well as interaction with RAW 264.7 macrophages. Interactions between the cells were simulated by incubating the 3T3- L1 adipocytes with secretions collected from RAW 264.7 macrophages and vice versa. DGAT1 was overexpressed in 3T3-L1 preadipocytes via recombinant lentivirus and resulted in a more than 16-fold increase in mRNA compared to control cells transduced with an “empty” reporter lentiviral vector. Prior to differentiation, the DGAT1 overexpressing preadipocytes showed elevated intracellular TAG accumulation and the formation of distinct lipid droplets, whereas the control cells did not demonstrate this behaviour. After differentiation, the increase in lipid was unexpectedly not maintained, characterised by a lower rate of lipogenesis and smaller adipocyte size. Assessment of adipocyte interactions with RAW 264.7 macrophages revealed both the recombinant DGAT1 and control vectors were associated with elevated inflammatory gene expression in response to macrophage secretions. Similarly, exposure to adipocyte secretions obtained from both populations of the transduced 3T3-L1 cells led to increased RAW 264.7 macrophage activation compared to secretory factors collected from non-transduced adipocytes. Genetic manipulation of 3T3-L1 cells by lentiviral transduction led to elevated inflammation which appeared to be due to activation of an immune response to the vector. Overexpression via the recombinant DGAT1 vector resulted in an unexpected reduction in adipocyte size which did not occur in the transduced control cells despite both populations having an impaired inflammatory profile. This loss of adipogenic behaviour was likely attributable to interference with the complex differentiation process due to an excessively high gene expression load, rather than the DGAT1 transgene itself. These results emphasise the need to exercise caution when using genetic manipulation techniques with the 3T3-L1 cell line, particularly because changes in inflammatory profile can occur without alterations in observable traits and may therefore be difficult to detect.

Subjects/Keywords: 3T3-L1; Adipocyte; Overexpression; DGAT1; Lentivirus; Transduction

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APA (6^th Edition):

Li, A. J. (2015). Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/14308

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Li, Alisha Jean-King. “Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction .” 2015. Thesis, University of Sydney. Accessed March 06, 2021. http://hdl.handle.net/2123/14308.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Li, Alisha Jean-King. “Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction .” 2015. Web. 06 Mar 2021.

Vancouver:

Li AJ. Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction . [Internet] [Thesis]. University of Sydney; 2015. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2123/14308.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Li AJ. Overexpression of DGAT1 in 3T3-L1 Cells by Lentiviral Transduction . [Thesis]. University of Sydney; 2015. Available from: http://hdl.handle.net/2123/14308

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

12. Ledger, Scott. Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection.

Degree: Clinical School - St Vincent's Hospital, 2016, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/56230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40347/SOURCE02?view=true

► HIV currently infects 35 million people worldwide and antiretroviral treatments are expensive, lifelong, and fail to provide a cure. Gene therapy provides an alternate approach… (more)

▼ HIV currently infects 35 million people worldwide and antiretroviral treatments are expensive, lifelong, and fail to provide a cure. Gene therapy provides an alternate approach to the treatment of HIV. I investigated the effects of two therapeutic genes both singly and in tandem: the fusion inhibiting membrane anchored peptide maC46 (C46), and a short-hairpin RNA to CCR5 (sh5) which downregulates expression of the CCR5 receptor. These genes were carried on lentiviral vectors which were transduced into cell lines and PBMC. The vectors were named Control, C46, sh5 and Dual. The therapeutic genes conferred selective advantages in the presence of the R5tropic HIV-1BaL, with the Dual construct displaying the strongest selective advantage as Dual gene-containing cells expanded significantly faster than either single-gene vector. Both the sh5 and Dual vectors conferred a survival advantage for the cultures, with significant resistance against cell death, as well as strong inhibition of viral replication. The therapeutic genes also conferred protection against pseudotyped HIV in single round infection assays, with the Dual construct performing the best and with the greatest consistency. While most protection conferred in Molt4/CCR5 was paralleled in PBMC, the sh5 construct yielded differing results in PBMC. The most likely explanation is that among the cells that comprise PBMC, some of them may express other receptors which can be utilised by the HIV strains used. Cells containing the therapeutic genes were also challenged to assess their potential to trap HIV on their surface. Results indicated the C46 (and Dual)-marked cells mediated viral trapping of HIV-1NL4-3. However, HIV-1BaL virion trapping was observed on sh5 and Dual marked cells, yet C46-marked cells behaved differently. Microscopy indicated potential viral trapping on C46-marked cells, while flow cytometric analysis showed that this virus was more likely within the cell membrane. This indicated that the processes of viral entry may differ (by more than just co-receptor use) between HIV-1NL4-3 and HIV-1BaL.The work conducted here points to there being complex interactions between virus and host cells around the points of viral attachment and entry. However, even with these undefined processes taking place, the combined gene therapy consistently provided the best protection on every metric assessed. Advisors/Committee Members: Symonds, Geoff, UNSW, Murray, John, UNSW.

Subjects/Keywords: shRNA; HIV; Gene therapy; CCR5; C46; lentivirus

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APA (6^th Edition):

Ledger, S. (2016). Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/56230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40347/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Ledger, Scott. “Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection.” 2016. Doctoral Dissertation, University of New South Wales. Accessed March 06, 2021. http://handle.unsw.edu.au/1959.4/56230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40347/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Ledger, Scott. “Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection.” 2016. Web. 06 Mar 2021.

Vancouver:

Ledger S. Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection. [Internet] [Doctoral dissertation]. University of New South Wales; 2016. [cited 2021 Mar 06]. Available from: http://handle.unsw.edu.au/1959.4/56230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40347/SOURCE02?view=true.

Council of Science Editors:

Ledger S. Use of Short-Hairpin RNA to CCR5, and maC46 Entry Inhibitor Gene-Therapies against HIV infection. [Doctoral Dissertation]. University of New South Wales; 2016. Available from: http://handle.unsw.edu.au/1959.4/56230 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:40347/SOURCE02?view=true

Johannes Gutenberg Universität Mainz

13. Zidan, Mohamed. Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells.

Degree: 2013, Johannes Gutenberg Universität Mainz

URL: http://ubm.opus.hbz-nrw.de/volltexte/2013/3478/

►

Die Suppression von autoreaktiven T-Zellen ist eine Funktion von CD4+CD25+ regulatorischen T-Zellen (CD4+CD25+ Tregs). CD4+CD25+ Tregs unterdrücken autoaggressive Immunantworten. Galectin-10 und Foxp3 sind wichtige Proteine,… (more)

▼

Die Suppression von autoreaktiven T-Zellen ist eine Funktion von CD4+CD25+ regulatorischen T-Zellen (CD4+CD25+ Tregs). CD4+CD25+ Tregs unterdrücken autoaggressive Immunantworten. Galectin-10 und Foxp3 sind wichtige Proteine, die an dem supprimierenden Mechanismus der Tregs beteiligt sind. Galectin-10 ist eines der ältesten bekannten humanen Proteine, die nicht in anderen Spezies gefunden worden sind. Foxp3 ist ein Transkriptionsfaktor, der in menschlichen CD4+CD25+ Tregs und in CD4+CD25- T-Effektor-Zellen nach Aktivierung exprimiert wird. Ein siRNA-vermittelter Knockdown dieses intrazellulären löslichen Proteins hebt die supprimierende Funktion der humanen CD4+CD25+ Tregs auf.rnDiese Arbeit beinhaltet in vitro durchgeführte Untersuchungen zur Ermöglichung eines Knockdown von Galectin-10 und/oder Foxp3 in humanisierten Mäusen. Es war möglich, ein Verfahren für die Produktion von lentiviralen Partikeln zu etablierten, die sich als effizientes Vehikel für den Gentransfer in humane Stammzellen und verschiedene Tumor- und Immunzellen erwiesen. Nach der Transduktion von AML14.3D10 Tumorzellen mit GFP-codierenden lentiviralen Partikeln konnte eine langfristige Expression von GFP erreicht werden. Außerdem war es möglich lentivirale Partikel zu erzeugen, die mit shRNA gegen Galectin-10 codiert waren. Die erzeugten Partikel erwiesen sich als funktionell, indem sie eine deutliche Herunterregulation von Galectin-10 in konstitutiv Galectin-10 exprimierenden AML14.3D10 Tumorzellen bewirkten. Unsere Studie präsentierte außerdem eine erstmalige Untersuchung zum Nachweis von Galectin-10-Protein in Eosinophilen aus humanen CD34+ hämatopoetischen Stammzellen (HSC). Diese stabile in vitro Galectin-10-Expression bietet ein alternatives Untersuchungsmodell zu CD4+CD25+ Tregs, die nicht aus CD34+ HSC differenziert werden können. Der zusätzliche Einbau des GFP-Gens in die mit shRNA gegen Galectin-10 codierende lentivirale Partikel war ein wichtiger Schritt zur Markierung von Zellen, die einen Galectin-10-Knockdown aufwiesen. Die neuen bicistronischen lentiviralen Partikel erwiesen sich sowohl in aus CD34+ HSC differenzierten Eosinophilen als auch in AML14.3D10 Zellen, die einen eosinophilen Phänotyp aufweisen, als funktionell. Schließlich konnte mit den bicistronischen lentiviralen Partikeln, die mit GFP und shRNA gegen Foxp3 codiert waren, eine Herunterregulation von Foxp3 in CD4+CD25- T-Effektor-Zellen erreicht werden, was erneut die erfolgreiche Herstellung von funktionellen lentiviralen Partikeln bewies.rn

The maintenance of tolerance to self is a function of CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs). CD4+CD25+ Tregs suppress inadequate and autoaggressive immune responses. Galectin-10 and Foxp3 are important proteins that participate in suppressive mechanisms of Tregs. Galectin-10 is one of the oldest known human-specific proteins which is not found in any other species. Foxp3 is a transcription factor expressed in human CD4+CD25+ Tregs and in activated CD4+CD25- T effector cells. siRNA-mediated knockdown of this intracellular…

Subjects/Keywords: Galectin-10, Foxp3, Tregs, Knockdown, Lentivirus; Galectin-10, Foxp3, Tregs, Knockdown, Lentivirus; Life sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zidan, M. (2013). Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2013/3478/

Chicago Manual of Style (16^th Edition):

Zidan, Mohamed. “Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells.” 2013. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed March 06, 2021. http://ubm.opus.hbz-nrw.de/volltexte/2013/3478/.

MLA Handbook (7^th Edition):

Zidan, Mohamed. “Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells.” 2013. Web. 06 Mar 2021.

Vancouver:

Zidan M. Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2013. [cited 2021 Mar 06]. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2013/3478/.

Council of Science Editors:

Zidan M. Lentivirus-mediated knockdown of Galectin-10 and Foxp3 in human immune cells. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2013. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2013/3478/

14. Hasegawa, Marjorie Yumi. Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta.

Degree: PhD, Clínica Veterinária, 2014, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07012015-081945/ ;

► Artrite Encefalite Caprina é uma enfermidade infecciosa, multissistêmica, causada pelo vírus da Artrite Encefalite Caprina, que pertence dentre os Lentivírus de Pequenos Ruminantes. Sobre o… (more)

▼ Artrite Encefalite Caprina é uma enfermidade infecciosa, multissistêmica, causada pelo vírus da Artrite Encefalite Caprina, que pertence dentre os Lentivírus de Pequenos Ruminantes. Sobre o aspecto reprodutivo na transmissão, o objetivo do presente estudo consiste em avaliar experimentalmente a transmissibilidade do lentivírus caprino em cabras e suas crias pela placenta e sêmen. Para avaliar a influência da transmissão via placentária, foram utilizadas cinco fêmeas com CAEV inseminadas artificialmente com sêmen de bode livre de CAEV. Para avaliar a influência da transmissão pelo sêmen, foram utilizadas seis fêmeas livres de CAEV inseminadas artificialmente com sêmen de bode livre de CAEV. O CAEV-Cork foi adicionado ao sêmen fresco com a finalidade de se obter título infectante com carga viral em 105 TCID50/mL. Como grupo controle, duas cabras livres de CAEV foram inseminadas artificialmente com sêmen de mesmo bode sem o inóculo viral; e outras duas cabras com CAEV inseminadas com a carga viral. As fêmeas foram monitoradas durante a gestação até 15 dias pós-parto e as crias separadas das mães foram monitoradas até 12 meses de idade, empregando-se as técnicas de IDGA, cELISA e nested-PCR. As fêmeas com CAEV apresentaram resultados positivos em IDGA (87,10%), cELISA (88,71%) e nested-PCR (25,81%). As crias apresentaram resultados negativos em ambos os testes de IDGA e cELISA, embora na técnica de nested-PCR, 7,14% das amostras apresentaram banda positiva. Das seis fêmeas livres de CAEV, quatro (66,67%) apresentaram soroconversão com 18,46% das amostras positivas ao IDGA, 49,23% das amostras positivas ao cELISA e nenhuma para nested-PCR. Anticorpos anti-CAEV foram detectados 30 dias pós IA. Quanto às crias, 5,26% e 11,28% das amostras apresentaram resultado positivo para IDGA e nested-PCR, respectivamente. Nenhuma amostra apresentou positividade para cELISA. O grupo controle livre de CAEV tiveram resultados negativos para as três técnicas, incluindo suas crias; enquanto que as fêmeas com CAEV inseminadas com o inóculo viral apresentaram 61,90% das amostras positivas para IDGA, 100% para cELISA e nenhuma amostra para nested-PCR. Suas crias obtiveram no total somente um resultado positivo para IDGA e outro para nested- PCR. A positividade encontrada em nested-PCR nas crias pode ter um significado particular de identificar animais infectados porém soronegativos, como em situações de soroconversão tardia. Entretanto, não é possível assumir a transmissão do CAEV para crias de forma insofismável, embora não é descartada a possibilidade de infecção das crias pelo sêmen e placenta com soroconversão tardia. Contudo é possível a transmissão do CAEV por IA com sêmen infectado em fêmeas livres de CAEV. A carga viral utilizada no estudo foi capaz de infectar as fêmeas. Com relação aos testes utilizados, o cELISA detectou a soroconversão mais cedo que o IDGA. A técnica de nested-PCR falhou em detectar a infecção antes da soroconversão nas fêmeas. Este estudo proporcionou maiores informações sobre a transmissão do lentivírus caprino… Advisors/Committee Members: Gregory, Lilian.

Subjects/Keywords: AGID; Caprine lentivirus; cELISA; cELISA; IDGA; Lentivirus caprino; Nested-PCR; Nested-PCR; Transmissão; Transmission

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hasegawa, M. Y. (2014). Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07012015-081945/ ;

Chicago Manual of Style (16^th Edition):

Hasegawa, Marjorie Yumi. “Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta.” 2014. Doctoral Dissertation, University of São Paulo. Accessed March 06, 2021. http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07012015-081945/ ;.

MLA Handbook (7^th Edition):

Hasegawa, Marjorie Yumi. “Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta.” 2014. Web. 06 Mar 2021.

Vancouver:

Hasegawa MY. Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta. [Internet] [Doctoral dissertation]. University of São Paulo; 2014. [cited 2021 Mar 06]. Available from: http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07012015-081945/ ;.

Council of Science Editors:

Hasegawa MY. Estudo sobre a transmissibilidade do vírus da artrite encefalite caprina através do sêmen e da placenta. [Doctoral Dissertation]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/10/10136/tde-07012015-081945/ ;

15. Bose, Deepanwita. Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène.

Degree: Docteur es, Virologie - Microbiologie - Immunologie, 2017, Université Grenoble Alpes (ComUE)

URL: http://www.theses.fr/2017GREAV009

► Notre laboratoire a développé un prototype de vaccin unique contre le VIH-1 / SIDA. C'est un un lentivecteur ADN non-intégratif qui a été testé dans… (more)

▼ Notre laboratoire a développé un prototype de vaccin unique contre le VIH-1 / SIDA. C'est un un lentivecteur ADN non-intégratif qui a été testé dans une étude pilote utilisant des modèles animaux. L'étude a montré la protection de tous les macaques (6/6) vaccinés et la réponse était composée de cellules effectrices (EM) et des cellules T mémoire centrale (CM). Plus important encore, elle contenait également des cellules antigène spécifique à haute capacité de prolifération contenant des cellules T mémoire de type cellule souche (TSCM). Durant le travail de cette thèse, le génome vaccinal a été encore amélioré en commutant son enveloppe dotée de tropisme CXCR4 contre des enveloppes à tropisme CCR5 de virus de clade B (WARO) obtenu à partir d'un patient infecté de façon chronique et de trois souches de VIH-1 de Clade C transmetteur foundateur (T/F) de patients Zambiens. Une deuxième amélioration du vaccin a été réalisée en modifiant le génome afin qu’il puisse incorporer des adjuvants moléculaires capables d'améliorer d’avantage son immunogénicité.Etant donné que le lentivirus humain VIH-1 a développé plusieurs stratégies complexes pour persister, l’autre partie de la thèse a été consacrée à développer un outil pour comprendre la latence dans les cellules T CD4 + de la mémoire infectée. Les cellules latentes ont des génomes d'ADN viral intégrés non exprimés. Un des principaux mécanismes de cette latence est l'absence de transactivation du promoteur LTR par Tat. Les développements récents de la thérapie antivirale hautement active (HAART) efficace pour contrôler les cellules infectées circulantes et dans les tissus reste inefficaces contre les cellules du réservoir composé de cellules infectées latentes. Un des obstacles pour ce type d'études est l'absence de prototypes de lentivirus de primates appropriés incapables de d’effectuer la latence pour s’en servir comme modèle d'infection extrême dans l'évaluation. Nous avons émis l'hypothèse qu'un génome SHIV réplicatifdont l’expression est sous le contrôle de LTR du CAEV, Tat-indépendant doté de promoteur constitutif constituera un outil précieux pour de telles études. Nous avons conçu des LTRs chimères de CAEV portant les séquences d'attachement de celles du SIV à leurs extrémités et nous les ont utilisés pour contrôler l’expression du génome complet de SHIV-KU2. La construction résultante est SHIV-YCC qui devrait générer un virus qui ne n’effectue pas de latence en absence de Tat. Nous avons observé que les cellules transfectées avec le génome SHIV-YCC produisent des protéines SHIV qui s’assemblent en particules infectieuses excrétées des cellules. Les virions sont capables d'infecter les lymphocytes T CD4 + cibles tant dans les PBMC primaires que dans les lignées cellulaires. Le passage en série du virus dans les PBMC de macaques augmente la réplication et l'infectiosité du virus. SHIV-YCC est le premier lentivirus chimérique réplicatif de primates qui exprime de manière constitutive toutes les protéines virales. Ce nouveau modèle offre la possibilité d'étudier les… Advisors/Committee Members: Chebloune, Yahia (thesis director).

Subjects/Keywords: Lentivirus; Promoteur; Réplication; Vih/vis; Caev; Immunité; Lentivirus; Promoter; Replication; Hiv/siv; Caev; Immunity; 610

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bose, D. (2017). Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène. (Doctoral Dissertation). Université Grenoble Alpes (ComUE). Retrieved from http://www.theses.fr/2017GREAV009

Chicago Manual of Style (16^th Edition):

Bose, Deepanwita. “Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène.” 2017. Doctoral Dissertation, Université Grenoble Alpes (ComUE). Accessed March 06, 2021. http://www.theses.fr/2017GREAV009.

MLA Handbook (7^th Edition):

Bose, Deepanwita. “Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène.” 2017. Web. 06 Mar 2021.

Vancouver:

Bose D. Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène. [Internet] [Doctoral dissertation]. Université Grenoble Alpes (ComUE); 2017. [cited 2021 Mar 06]. Available from: http://www.theses.fr/2017GREAV009.

Council of Science Editors:

Bose D. Tat-independent lentivirus genomes for vaccination and host/pathogen interaction studies : Génomes de lentivirus Tat indépendants pour des études de vaccination et les interactions hôte/pathogène. [Doctoral Dissertation]. Université Grenoble Alpes (ComUE); 2017. Available from: http://www.theses.fr/2017GREAV009

16. Ahmid, Simaa. Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence.

Degree: Docteur es, Virologie - Microbiologie - Immunologie, 2017, Université Grenoble Alpes (ComUE)

URL: http://www.theses.fr/2017GREAV018

►

Le syndrome d'immunodéficience acquise (SIDA) est une maladie provoquée chez l'homme par le virus de l'immunodéficience humaine (VIH), un lentivirus à ARN monocaténaire qui infecte… (more)

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Le syndrome d'immunodéficience acquise (SIDA) est une maladie provoquée chez l'homme par le virus de l'immunodéficience humaine (VIH), un lentivirus à ARN monocaténaire qui infecte les cellules humaines qui expriment les CD4 à leur surface. Depuis son apparition en 1982 chez l’homme, il y a eu environ 80 millions d'individus infectés dans le monde et près de la moitié d'entre eux sont déjà décédés. Aucun vaccin n'existe actuellement mais l'espérance de vie d’un grand nombre de patients est maintenant prolongée grâce au développement et la disponibilité d'un traitement antirétroviral hautement actif (HAART en anglais). En raison de la complexité des interactions hôte/pathogène liées à l'infection par le VIH-1 chez l'homme et les modèles primates non-humains actuels, le développement d’un modèle plus simple est nécessaire pour étudier et mieux comprendre les mécanismes sous-jacents de l'augmentation de la pathogenèse du VIH-1 chez l’humain. Dans ce but, un virus chimérique CAL-HIV-R1 a été construit dans notre laboratoire en échangeant les longues séquences répétées terminales (LTR) du VIH par celles du CAEV, un lentivirus caprin. Parce que ces LTR de CAEV ont un promoteur constitutif qui est indépendant du trans-activateur de la transcription, ce virus chimérique ne devrait pas subir de latence dans les cellules T CD4+ mémoire. Pour rendre son efficacité réplicative plus performante, cette chimère a subi plusieurs passages successifs sur des cellules humaines en culture. En plus de la présence de son récepteur primaire, la protéine CD4, le VIH doit interagir avec une seconde molécule co-réceptrice pour entrer dans la cellule hôte. Des clones moléculaires infectieux contenant des génomes proviraux complets de plusieurs isolats de VIH-1 ont été reçus de la banque de produits "NIH AIDS Reagent Program Repository". Trois d'entre eux, à savoir pNL4-3, p89.6 et WARO, ont été utilisés pour produire des stocks de virus après transfection des cellules de la lignée humaine HEK-293T et utilisés pour infecter d’autres lignées cellulaires telles que : 1) des cellules GHOST, utilisées pour examiner le tropisme des virus en fonction de leur utilisation des co-récepteurs et qui sont respectivement X4, X4/R5 et R5; 2) la lignée cellulaire M8166, utilisée comme cellules indicatrices du fait de ses propriétés fusogéniques, et qui sert à examiner les capacités de réplication et enfin, 3) la lignée cellulaire TZM-bl utilisée pour évaluer le titre infectieux des virus. Par ailleurs, un vaccin basé sur un vecteur ADN lentiviral chimérique, le CAL-SHIV-IN-, a été développé au laboratoire et testé chez des macaques. Dans le cadre de cette étude, un test de séro-neutralisation a été réalisé sur des échantillons de sérum des macaques vaccinés avec ce vecteur, et des animaux témoins, pour examiner la présence d'anticorps pouvant neutraliser le virus. Bien que des anticorps furent présents aucune capacité neutralisante n'a pu être détectée.

Acquired Immuno-Deficiency Syndrome (AIDS) is a disease caused by immunodeficiency viruses in human…

Advisors/Committee Members: Chebloune, Yahia (thesis director).

Subjects/Keywords: Lentivirus; Pathogénèse; Latence; Persistence; Atténuation; Lentivirus; Pathogenesis; Latency; Persistence; Attenuation; 616.91; 579.2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ahmid, S. (2017). Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence. (Doctoral Dissertation). Université Grenoble Alpes (ComUE). Retrieved from http://www.theses.fr/2017GREAV018

Chicago Manual of Style (16^th Edition):

Ahmid, Simaa. “Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence.” 2017. Doctoral Dissertation, Université Grenoble Alpes (ComUE). Accessed March 06, 2021. http://www.theses.fr/2017GREAV018.

MLA Handbook (7^th Edition):

Ahmid, Simaa. “Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence.” 2017. Web. 06 Mar 2021.

Vancouver:

Ahmid S. Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence. [Internet] [Doctoral dissertation]. Université Grenoble Alpes (ComUE); 2017. [cited 2021 Mar 06]. Available from: http://www.theses.fr/2017GREAV018.

Council of Science Editors:

Ahmid S. Analyse fonctionnelle de génomes lentiviraux de primates réplicatifs sous le contrôle des promoteurs du lentivirus caprin CAEV : Modèle d'étude pour la latence et persistance des lentivirus : Functional analysis of replication-competent primate lentivirus genomes driven by CAEV promoters : A new model to study latency and persistence. [Doctoral Dissertation]. Université Grenoble Alpes (ComUE); 2017. Available from: http://www.theses.fr/2017GREAV018

17. Antonia Regina Sessa da Silva. Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão.

Degree: 2007, Universidade Federal Rural do Rio de Janeiro

URL: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=807

►

O Brasil possui atualmente o segundo maior rebanho de eqüídeos do mundo e a Eqüideocultura Brasileira desempenha um importante papel no desenvolvimento do setor de… (more)

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O Brasil possui atualmente o segundo maior rebanho de eqüídeos do mundo e a Eqüideocultura Brasileira desempenha um importante papel no desenvolvimento do setor de agronegócios. Entre as doenças infecciosas que afetam a eqüinocultura nacional, a Anemia Infecciosa dos Eqüinos (AIE) tem se mostrado de difícil controle. A AIE é causada por um retrovírus, apresenta uma distribuição mundial, e é reconhecida como a mais importante doença dos eqüinos. Entre os sinais clínicos mais comuns, na fase aguda da doença, encontram-se a anemia seguida de icterícia nas mucosas, edema ventral, mioglobinúria, caquexia e, principalmente, febre intermitente. Como não há tratamento, Ministério da Agricultura, Pecuária e Abastecimento (MAPA) determina, através de mecanismo legais, uma política de exame obrigatório em laboratórios credenciados, para o transporte e comercialização de eqüídeos no País. O exame é baseado na prova de Coggins, uma imunodifusão em ágar gel do soro do animal testado contra antígeno do vírus da AIE. Como a infecção é vitalícia, animais soropositivos são eutanasiados por Médicos Veterinários do MAPA. Considerando que a precisão dos resultados é crítica, posto que animais falso positivos podem ser sacrificados inutilmente, e falso negativos preservados como fonte de infecção, surgiu o interesse de um análise sistemática da reprodutibilidade dos kits e possíveis fontes de erro no diagnóstico. Para esta finalidade, soros positivos e negativos, referenciados pela repetição dos testes de Coggins e ELISA, foram avaliados pela prova de IDGA, comparativamente com três kits de diferentes fabricantes. Nos experimentos de reprodutibilidade, observou-se uma grande distinção na qualidade da linha de precipitação promovida pelos soros positivos nos testes nos diferentes kits. Este fenômeno pode ser justificado pela utilização das condições técnicas legais, determinadas por portaria do MAPA, que são distintas das recomendações dos fabricantes de dois dos kits analisados. Mesmo assim, a avaliação da reprodutibilidade dos resultados dos kits com os soros referenciados mostrou elevada correlação.

Brazil has currently the second bigger flock of equines of the world and the brazilian equines breeding plays an important role in the development of the sector of agribusiness. Among the infectious disease that affect the national equines breeding, the Equine infectious anemia (EIAV) has been shown of difficult control. The Equine infectious anemia is caused by a retrovirus, it has a worldwide distribution, and it is recognized as the most important disease of equines. The most common clinical signals in the acute phase, are anemia followed of jaundice in the mucosae, ventral oedema, mioglobinury, caquexy and, mainly, intermittent fever. Once it has no treatment, Ministry of Agriculture, Cattle and Supplying determines, through legal mechanisms, a politics of obligatory examination in credentialed laboratories, for the transport and commercialization of equines in the country. The examination is based on the test of Coggins, an…

Advisors/Committee Members: Maria das Gracas Miranda Danelli, Carlos Mazur.

Subjects/Keywords: anemia infecciosa eqüina; eqüinos; eqüídeos; lentivirus; retrovirus; diagnóstico e IDGA.; MEDICINA VETERINARIA; equine infectious anemia; equines; lentivirus; retrovirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Silva, A. R. S. d. (2007). Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão. (Thesis). Universidade Federal Rural do Rio de Janeiro. Retrieved from http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=807

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Silva, Antonia Regina Sessa da. “Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão.” 2007. Thesis, Universidade Federal Rural do Rio de Janeiro. Accessed March 06, 2021. http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=807.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Silva, Antonia Regina Sessa da. “Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão.” 2007. Web. 06 Mar 2021.

Vancouver:

Silva ARSd. Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão. [Internet] [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2007. [cited 2021 Mar 06]. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=807.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Silva ARSd. Diagnóstico da Anemia Infecciosa Eqüina: análise comparativa de sistemas comerciais de diagnóstico por imunodifusão. [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2007. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=807

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

18. Chougui, Ghina. Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr.

Degree: Docteur es, Microbiologie, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCB080

►

Les rétrovirus VIH-1 et 2 responsables du SIDA, bien que très similaires sur le plan de leur organisation génomique, diffèrent par leurs protéines auxiliaires. Ces… (more)

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Les rétrovirus VIH-1 et 2 responsables du SIDA, bien que très similaires sur le plan de leur organisation génomique, diffèrent par leurs protéines auxiliaires. Ces dernières inactivent des facteurs cellulaires antiviraux et permettent ainsi l'établissement d'un environnement cellulaire favorable à la réplication virale. Vpx, une protéine auxiliaire spécifique du VIH-2, est connue pour sa capacité à augmenter l'infection virale, une activité longtemps reliée à son unique faculté à contrecarrer SAMHD1, un facteur de restriction actif à l'étape de transcription inverse. Cependant, plusieurs éléments de la littérature suggèrent que Vpx confère un avantage au virus indépendamment de SAMHD1. Nous avons donc étudié la possibilité d'une cible supplémentaire inactivée par Vpx et, à partir d'un crible protéomique, nous avons identifié le complexe HUSH (HUman Silencing Hub). Composé de TASOR, MPP8 et Periphilin, le complexe HUSH est impliqué dans le control épigénétique de transgènes intégrés ainsi que des éléments transposables Line-1. Nous avons montré la capacité de Vpx à lier le complexe HUSH et à induire sa dégradation par le protéasome grâce au détournement de l'adaptateur d'ubiquitine ligase DCAF-1 et ce, de façon indépendante de SAMHD1. De ce fait, Vpx est capable de réactiver des provirus latents du VIH, contrairement à des mutants de Vpx incapables d'induire une dégradation de HUSH. Bien que l'antagonisme du complexe HUSH humain ne soit pas conservé au sein de toutes les lignées lentivirales, y compris le VIH-1, il est une caractéristique de certains Vpr des VIS des singes verts africains ainsi que du VIS divergent du singe de l'Hoest. Le caractère ancien de cette fonction post-intégrative insoupçonnée des gènes vpx/vpr, ainsi que la spécificité d'espèces observée, sont deux critères favorables au statut de facteur de restriction pour le complexe HUSH. Dressant ainsi le contrôle épigénétique comme barrière de l'immunité intrinsèque, nécessaire au maintien de l'intégrité du génome cellulaire.

HIV-1 and 2 are both responsible for AIDS, though similar, these two retroviruses harbour different sets of auxiliary proteins. Through the inactivation of cellular antiviral factors, these auxiliary proteins allow the establishment of a favourable environment for viral replication. Vpx, an HIV-2 only auxiliary protein, is known for its ability to increase viral infection, which was long linked to its sole capacity to counteract SAMHD1, a restriction factor active at the reverse transcription step. However, several lines of evidence suggested a SAMHD1-independent advantage of Vpx. We therefore investigated the possibility of an additional Vpx target and through a proteomic screen, we identified the HUman Silencing Hub (HUSH) complex. HUSH complex, including: TASOR, MPP8 and Periphelin, was reported to epigenetically silence integrated transgenes and recently Line-1 transposable elements. Here, we show that Vpx binds the HUSH complex and induces its proteasomal degradation through the hijacking of the DCAF-1 ubiquitin ligase…

Advisors/Committee Members: Margottin-Goguet, Florence (thesis director).

Subjects/Keywords: Lentivirus; Vih; Vpr; Vpx; Facteur de restriction; Complexe HUSH; Lentivirus; Hiv; Vpr; Vpx; Restriction factor; HUSH complex; 579.25

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chougui, G. (2018). Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCB080

Chicago Manual of Style (16^th Edition):

Chougui, Ghina. “Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed March 06, 2021. http://www.theses.fr/2018USPCB080.

MLA Handbook (7^th Edition):

Chougui, Ghina. “Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr.” 2018. Web. 06 Mar 2021.

Vancouver:

Chougui G. Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Mar 06]. Available from: http://www.theses.fr/2018USPCB080.

Council of Science Editors:

Chougui G. Antagonism of HUSH restriction by lentiviral Vpx and Vpr proteins : Antagonisme de la restriction du complexe HUSH par les protéines lentivirales Vpx et Vpr. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCB080

NSYSU

19. Chen, Man-Jing. Remote control of lentivirus for RNA interference therapy.

Degree: Master, Institute of Medical Science and Technology, 2016, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0725116-122157

► Clinical virotherapy has been successfully approved for use in cancer treatment by the US Food and Drug Administration (FDA). Innovative treatment of cancer, oncolytic viruses… (more)

Subjects/Keywords: RNA interference; Short hairpin RNA; Micro-transduction; Lentivirus; Magnetic nanoparticles

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, M. (2016). Remote control of lentivirus for RNA interference therapy. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0725116-122157

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Man-Jing. “Remote control of lentivirus for RNA interference therapy.” 2016. Thesis, NSYSU. Accessed March 06, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0725116-122157.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Man-Jing. “Remote control of lentivirus for RNA interference therapy.” 2016. Web. 06 Mar 2021.

Vancouver:

Chen M. Remote control of lentivirus for RNA interference therapy. [Internet] [Thesis]. NSYSU; 2016. [cited 2021 Mar 06]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0725116-122157.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen M. Remote control of lentivirus for RNA interference therapy. [Thesis]. NSYSU; 2016. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0725116-122157

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

California State University – Northridge

20. Kawashima, Ryoko Lala. Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1.

Degree: MS, Chemistry and Biochemistry, 2014, California State University – Northridge

URL: http://hdl.handle.net/10211.2/5013

► Atherosclerosis is an inflammatory disorder triggered by an accumulation of cholesterol in macrophage-derived foam cells. Adherence of these cells to the vascular endothelium, leads to… (more)

▼ Atherosclerosis is an inflammatory disorder triggered by an accumulation of cholesterol in macrophage-derived foam cells. Adherence of these cells to the vascular endothelium, leads to cardiovascular disease. Removal of excess cellular cholesterol is essential to maintain a balanced cellular lipid profile and to oppose the development of atherosclerosis. The ATP-binding cassette transporter A1 (ABCA1) mediates the unidirectional efflux of excess cholesterol and phospholipids from foam cells to lipid-poor apolipoprotein A-I, in a process called reverse cholesterol transport, resulting in high-density lipoprotein (HDL) biogenesis. Lipoprotein lipase (LPL) is a lipolytic enzyme expressed by macrophages within atherosclerotic lesions, and is considered proatherogenic. The aim of this study was to investigate the regulatory effects of LPL on ABCA1-mediated cholesterol efflux. This was accomplished using three approaches: lentivirus-mediated LPL gene silencing, chemical inhibition of LPL, and exogenous addition of LPL to the cell culture medium. First, stable THP-1 macrophage cell lines exhibiting LPL knockdown and LPL overexpression were successfully created, and confirmed using PCR methods. Since the level of LPL overexpression was modest, the rest of the study focused on the LPL knockdown cell line. Down-regulation of LPL protein levels was confirmed by metabolic labeling using 35S-methionine. Suppression of LPL expression increased ABCA1 mRNA levels, however there was no increase in ABCA1 protein levels detected through Western blotting. Furthermore, genes for the other modes of cholesterol efflux, ABCG1 and SR-BI, were down-regulated by 12% and 19%, respectively, in LPL knockdown cells. Knockdown cells, when used in a cholesterol efflux assay, revealed a significant increase in ABCA1-mediated cholesterol efflux compared to wild-type cells. The second approach was to inhibit LPL function in WT cells. Orlistat, an inhibitor of LPL lipase activity, when added to the culture medium, up-regulated ABCA1-independent cholesterol efflux. A LPL-specific antibody was used to inhibit the adapter function of LPL. Such an approach has been shown to interfere with the ability of LPL to promote apoA-I binding to the cell surface. The presence of anti-LPL IgY also up-regulated ABCA1-independent cholesterol efflux. Last, the addition of exogenous LPL resulted in a down-regulation of ABCA1-mediated cholesterol efflux in both wild-type and knockdown cells. These findings suggest an inverse correlation between LPL levels and ABCA1 cholesterol transport activity. Advisors/Committee Members: Medh, Jheem D. (advisor), Fischhaber, Paula L. (committee member).

Subjects/Keywords: Lentivirus (siRNA) technology; Dissertations, Academic – CSUN – Chemistry and Biochemistry – Biochemistry.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kawashima, R. L. (2014). Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1. (Masters Thesis). California State University – Northridge. Retrieved from http://hdl.handle.net/10211.2/5013

Chicago Manual of Style (16^th Edition):

Kawashima, Ryoko Lala. “Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1.” 2014. Masters Thesis, California State University – Northridge. Accessed March 06, 2021. http://hdl.handle.net/10211.2/5013.

MLA Handbook (7^th Edition):

Kawashima, Ryoko Lala. “Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1.” 2014. Web. 06 Mar 2021.

Vancouver:

Kawashima RL. Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1. [Internet] [Masters thesis]. California State University – Northridge; 2014. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/10211.2/5013.

Council of Science Editors:

Kawashima RL. Regulatory functions of lipoprotein lipase on the cholesterol transporter ATP-binding cassette transporter A1. [Masters Thesis]. California State University – Northridge; 2014. Available from: http://hdl.handle.net/10211.2/5013

Penn State University

21. Kazi, Abid A. ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11847

► PRAS40 and DEPTOR are mTOR binding proteins that affect cell metabolism. Under catabolic conditions such as sepsis and glucocorticoid excess, there is an increase in… (more)

▼ PRAS40 and DEPTOR are mTOR binding proteins that affect cell metabolism. Under catabolic conditions such as sepsis and glucocorticoid excess, there is an increase in total DEPTOR protein and a reduction in phosphorylation of PRAS40, suggesting that these proteins may modulate the mTOR-mediated protein synthetic response under normal and diseased conditions. The hypothesis of the present study was that knock down (KD) of PRAS40 or DEPTOR in C2C12 myocytes will increase protein synthesis via stimulating mTOR-S6K1 signaling. PRAS40 and DEPTOR KD was achieved using lentiviral particles containing shRNA to target the mouse PRAS40 and DEPTOR mRNA sequence, whereas control cells were transfected with a scrambled control shRNA. KD reduced PRAS40 and DEPTOR mRNA and protein content by 90%. PRAS40 KD did not result in increased phosphorylation of mTOR substrates or increased protein synthesis, whereas, DEPTOR KD increased both phosphorylation of mTOR kinase substrates, 4E-BP1 and S6K1, and protein synthesis. The responsiveness of PRAS40 and DEPTOR KD myocytes to anabolic (IGF-I) and catabolic (AICAR) stimuli was unaltered. Both PRAS40 and DEPTOR KD myoblasts were larger in diameter and exhibited an increased mean cell volume compared to scramble control. PRAS40 KD cells had decreased phosphorylation (S807/S811) of pRb protein. In contrast, DEPTOR KD cells had an increased phosphorylation (S807/S811) of pRb protein which is critical for the G1-S phase transition, coincident with an increased percentage of cells in the S phase. Neither PRAS40 nor DEPTOR KD altered myoblast apoptosis as evidenced by the lack of change for cleaved caspase-3. Although DEPTOR KD myoblasts did not alter autophagy as determined by a lack of change in the ratio of LC3BII/LC3BI, PRAS40 KD myoblasts had a reduced ratio of LC3BII/LC3BI. While PRAS40 KD delayed myotube formation concurrent with delayed proliferation, DEPTOR KD had the opposite effect on myogenesis and proliferation. Finally, while in vivo DEPTOR KD (~50% reduction) by electroporation into the muscle of C57/BL6 mice did not alter weight or protein synthesis in the control muscle, it prevented atrophy produced by 3 days of hindlimb immobilization, at least in part by increasing protein synthesis. Thus, our data support the hypothesis that PRAS40 and DEPTOR are important regulators of protein metabolism in myocytes and demonstrate that, while PRAS40 is required for normal myoblast growth and function, decreasing DEPTOR expression is sufficient to ameliorate the atrophic response produced by immobilization. Advisors/Committee Members: Charles H Lang, Dissertation Advisor/Co-Advisor, Charles H Lang, Committee Chair/Co-Chair, Scot R Kimball, Committee Member, Lisa M Shantz, Committee Member, Timothy M Ritty, Committee Member.

Subjects/Keywords: protein synthesis; mTOR; knockdown; lentivirus; shRNA; sepsis; disuse atrophy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kazi, A. A. (2011). ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11847

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kazi, Abid A. “ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES .” 2011. Thesis, Penn State University. Accessed March 06, 2021. https://submit-etda.libraries.psu.edu/catalog/11847.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kazi, Abid A. “ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES .” 2011. Web. 06 Mar 2021.

Vancouver:

Kazi AA. ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 06]. Available from: https://submit-etda.libraries.psu.edu/catalog/11847.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kazi AA. ROLE OF PRAS40 AND DEPTOR – TWO mTOR BINDING PROTEINS IN C2C12 MYOCYTES . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11847

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

22. Tessanne, Kimberly J. Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference.

Degree: PhD, Veterinary Physiology, 2012, Texas A&M University

URL: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7594

► RNA interference (RNAi) is a means of regulating gene expression by targeting mRNA in a sequence-specific manner for degradation or translational inhibition. Short hairpin RNAs… (more)

▼ RNA interference (RNAi) is a means of regulating gene expression by targeting mRNA in a sequence-specific manner for degradation or translational inhibition. Short hairpin RNAs (shRNAs) and short interfering RNAs (siRNAs) have been extensively employed for manipulating gene expression in a wide range of species. The goal for this research was to produce transgenic livestock in which myostatin, a negative regulator of muscle growth, has been targeted for silencing by RNAi. This would demonstrate the utility of RNAi for reducing gene expression in large animal species. To successfully target the myostatin gene for reduction, siRNAs were designed to target the both the bovine and caprine myostatin mRNA sequence. These were then tested for effectiveness in vitro using both an HEK 293T cell line expressing caprine myostatin as well as adult bovine muscle cells. The most effective siRNA, GDF8-1026, was cloned into a lentiviral plasmid and used to transduce bovine fetal fibroblasts for somatic cell nuclear transfer cloning as well as perivitelline injection of in vitro produced bovine embryos. To date, seven pregnancies have been established using these two methods. Concern over the possibility of off-target effects associated with the expression of shRNAs in vivo prompted investigation into tissue-specific expression. Therefore, investigation into the use of a muscle-specific promoter to drive transgene expression was pursued. The bovine myogenin promoter and muscle creatine kinase (MCK) promoter were cloned into a lentiviral plasmid and evaluated in bovine fetal muscle cells and mouse C2C12 cells in vitro for their ability to drive GFP expression. Both promoters demonstrated an increase in GFP intensity at day nine of differentiation when compared to the nontransduced control. The retroviral basis of lentiviral plasmids has raised concern over the possible development of replication competent lentivirus (RCL). Therefore, analysis of tissues from recipients of lentivirus-treated embryos was performed to detect possible RCL. Tissues and blood serum were tested for RCL using p24 ELISA as well as qRT-PCR for the VSV-G gene. To date all tissues tested so far shown no evidence for RCL using these analyses. Analysis of offspring transgenic for an shRNA targeting myostatin will allow confirmation of RNAi as a useful tool for manipulating gene expression in large animal species. Advisors/Committee Members: Westhusin, Mark (advisor), Long, Charles (committee member), Spencer, Thomas (committee member), Ing, Nancy (committee member).

Subjects/Keywords: transgenic; lentivirus; myostatin

…65 68 74 78 REPLICATION COMPETENT LENTIVIRUS (RCL) ANALYSIS IN RECIPIENT ANIMALS… …injection of lentivirus at the zygote stage .............................. 73 14 Transgenic… …competent lentivirus (RCL).39 Therefore, tests to detect these potential RCL are… …only expressed during in vitro production of recombinant lentivirus.42 Of these same 21… …recombinant lentivirus 17 can be injected into an oocyte or zygote prior to embryo transfer in…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tessanne, K. J. (2012). Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7594

Chicago Manual of Style (16^th Edition):

Tessanne, Kimberly J. “Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference.” 2012. Doctoral Dissertation, Texas A&M University. Accessed March 06, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7594.

MLA Handbook (7^th Edition):

Tessanne, Kimberly J. “Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference.” 2012. Web. 06 Mar 2021.

Vancouver:

Tessanne KJ. Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference. [Internet] [Doctoral dissertation]. Texas A&M University; 2012. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7594.

Council of Science Editors:

Tessanne KJ. Development of Transgenic Livestock with Reduced Myostatin Expression Using RNA Interference. [Doctoral Dissertation]. Texas A&M University; 2012. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7594

North Carolina State University

23. Jia, Bin. Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction.

Degree: PhD, Comparative Biomedical Sciences, 2004, North Carolina State University

URL: http://www.lib.ncsu.edu/resolver/1840.16/5331

► Equine infectious anemia virus (EIAV) is a macrophage-tropic lentivirus of horses. EIAV is unique among lentiviruses in that a further cleavage event occurs within the… (more)

Subjects/Keywords: EIAV; cytoplasmic tail; lentivirus pathogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jia, B. (2004). Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction. (Doctoral Dissertation). North Carolina State University. Retrieved from http://www.lib.ncsu.edu/resolver/1840.16/5331

Chicago Manual of Style (16^th Edition):

Jia, Bin. “Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction.” 2004. Doctoral Dissertation, North Carolina State University. Accessed March 06, 2021. http://www.lib.ncsu.edu/resolver/1840.16/5331.

MLA Handbook (7^th Edition):

Jia, Bin. “Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction.” 2004. Web. 06 Mar 2021.

Vancouver:

Jia B. Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction. [Internet] [Doctoral dissertation]. North Carolina State University; 2004. [cited 2021 Mar 06]. Available from: http://www.lib.ncsu.edu/resolver/1840.16/5331.

Council of Science Editors:

Jia B. Role of the Cytoplasmic Tail of Equine Infectious Anemia Virus Transmembrane Glycoprotein in Acute Disease Induction. [Doctoral Dissertation]. North Carolina State University; 2004. Available from: http://www.lib.ncsu.edu/resolver/1840.16/5331

University of Adelaide

24. Stocker, Alice. Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression.

Degree: 2010, University of Adelaide

URL: http://hdl.handle.net/2440/65308

► Cystic Fibrosis (CF) is the most common, fatal autosomal recessive disorder affecting the Caucasian population with a frequency of 1 in 2500 live births and… (more)

▼ Cystic Fibrosis (CF) is the most common, fatal autosomal recessive disorder affecting the Caucasian population with a frequency of 1 in 2500 live births and has a current median survival age of approximately 33 years. Characteristics of CF include abnormalities in sweat glands, malnutrition, pancreatic disease and infertility. It is however, severe and chronic lung disease that currently accounts for greater than 95% of morbidity and mortality in CF patients. The CF transmembrane conductance regulator gene was discovered in 1989 and in vitro correction of the defect soon followed, providing the basis for gene therapy as a potential cure for CF lung disease. To date, the lack of an efficient gene transfer vector system combined with the physical barriers of the airway epithelium limit the successful application of CF gene therapy. The work described in this thesis utilised a unique gene therapy approach developed by the CF Gene Therapy Research Group, which involved airway pre-treatment followed by gene delivery. Pre-treatment was with the natural detergent lysophosphatidylcholine (LPC), followed by a single-dose of a HIV-1 based lentivirus (LV) vector in vivo. Previously studies found significant gene expression within airway tissues, but areas of cell damage were also sometimes evident. Initial work included examining the relationship between gene transfer, LPC dose and timing parameters, and airway epithelial damage. This study found that 0.3% LPC followed 60 minutes later with the LV produced significant gene expression within the airway, with only mild airway epithelial disturbance observed. The longevity of LV-mediated gene expression was then evaluated in the nasal airway of C57Bl/6 mice using the LacZ marker gene. Treatment of mouse nasal airway epithelium with the LPC prior to instillation of a single dose of an LVLacZ vector produced significant LacZ gene expression in many mice for at least 18 months. The finding of gene expression in one mouse after 24 months indicated essentially lifetime gene expression had been achieved. We found that a single dose of LVLacZ produced immediate as well as lifetime mouse airway expression, confirming our hypothesis that use of an integrating vector extends transgene expression. Importantly, LVCFTR dosing achieved at least 12 months of CFTR expression, representing partial functional correction of the CFTR defect in CF knockout mice. These findings provide evidence that a single-dose Lentiviral gene transfer method may offer a novel in vivo therapeutic paradigm in the pursuit of a cure for CF airway disease. Advisors/Committee Members: Parsons, David Webb (advisor), Anson, Donald Stewart (advisor), School of Molecular and Biomedical Science (school).

Subjects/Keywords: cystic fibrosis; gene therapy; airway; lungs; respiratory; lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Stocker, A. (2010). Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/65308

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Stocker, Alice. “Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression.” 2010. Thesis, University of Adelaide. Accessed March 06, 2021. http://hdl.handle.net/2440/65308.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Stocker, Alice. “Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression.” 2010. Web. 06 Mar 2021.

Vancouver:

Stocker A. Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2440/65308.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Stocker A. Towards gene therapy for cystic fibrosis airway disease: development of single-dose lentiviral gene transfer for lifetime airway expression. [Thesis]. University of Adelaide; 2010. Available from: http://hdl.handle.net/2440/65308

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston University

25. Saxena, Debashree. Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation.

Degree: 2016, Boston University

URL: http://hdl.handle.net/2144/18730

► Lysyl oxidase like-2 (LOXL2) was found to be present extracellularly in primary human gingival fibroblast cells. This project has been primarily focused on investigating our… (more)

Subjects/Keywords: Molecular biology; CCN2; LOXL2; rLOXL2; Collagen accumulation; Lentivirus; Proliferation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Saxena, D. (2016). Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation. (Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/18730

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Saxena, Debashree. “Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation.” 2016. Thesis, Boston University. Accessed March 06, 2021. http://hdl.handle.net/2144/18730.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Saxena, Debashree. “Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation.” 2016. Web. 06 Mar 2021.

Vancouver:

Saxena D. Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation. [Internet] [Thesis]. Boston University; 2016. [cited 2021 Mar 06]. Available from: http://hdl.handle.net/2144/18730.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Saxena D. Two functions of lysyl oxidase like-2 : extracellular matrix maturation and cell proliferation. [Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/18730

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Michigan Technological University

26. Salehi, Nasrin. ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT.

Degree: PhD, Department of Chemical Engineering, 2016, Michigan Technological University

URL: https://digitalcommons.mtu.edu/etdr/245

► Localizing the drug at the site of action is one of the most important goals of drug delivery systems. This requires developing a vehicle… (more)

▼ Localizing the drug at the site of action is one of the most important goals of drug delivery systems. This requires developing a vehicle which is able to protect drug carriers from degradation, while delivering the drug of interest to the specific tissue. In this study, a novel recombinant protein RGD-CD47-Streptavidin was synthesized to modify the surface of the drug carriers, and thereby allow them to surpass the mononuclear phagocyte system and deliver the drug of interest directly to target cancer cells. The recombinant protein was made and purified using a unique solution containing low concentration of the non-ionic detergent Triton X-100 followed with alkaline buffer. The purified protein was characterized by the western blot analysis and its tumor tropic and antiphagocytic functionality was confirmed by the cell assay. Non-viral and viral drug carries were both functionalized with the recombinant multifunctional protein. As a model of non-viral drug carriers, 1.510⁷biotin coated polystyrene particles (150, 560 and 840 nm) were coated with various concentrations of the recombinant fusion protein. Flow cytometry and J774A.1 macrophage cell studies revealed that CD47 immobilized on the various size of particles significantly reduced phagocytosis for 8 hours. However, the soluble CD47 decreased the phagocytes’ particle engulfment just for 2 hours. The phagocytosis index was decreased by increasing the CD47 density on the particle surface. The results demonstrated that presence of 116.49, 45.33 and 287.58 µg/µm²of CD47-SA respectively on the surface of 840, 560 and 150 nm particles, decreased 50% of phagocytosis after 4 hours. To functionalize viral vectors with the multifunctional protein, lentivirus encoding eGFP was obtained from 293T producer cells and biotinylated by host-cell-assisted labeling strategy. The biotinylated lentivirus was coated with recombinant fusion protein RGD-CD47-SA and characterized by immunoblot analysis. The antiphagocytosis cell study and flow cytometry analysis demonstrated that CD47 self-marker protein potentially inhibited lentivirus uptake by macrophages and therefore decreased infectivity of the virus in comparison with non-CD47 coated virus. To examine the tumor targeting of the protein, the 560 nm polystyrene particles were coated with CD47-SA and RGD-CD47-SA recombinant fusion protein separately. The coated particles were able to escape from macrophage engulfment by 8 hours. The association of coated particles with integrin α_vβ₃ was demonstrated in the highly expressed integrin colorectal cancer cells (HT29) and adenocarcinomic human alveolar basal epithelial cells (A549). The polystyrene particles coated with CD47-SA were able to bind to the integrin α_vβ₃ expressed on the surface of the A549 and HT29 cells but not stronger than the particles coated with RGD-CD47-SA. After blocking the integrin α_vβ₃, the cellular uptake of functionalized nanoparticles with CD47 and… Advisors/Committee Members: Ching-An Peng.

Subjects/Keywords: CD47; Antiphagocytosis; Cancer; Targeting; Lentivirus; RGD; Molecular Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Salehi, N. (2016). ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT. (Doctoral Dissertation). Michigan Technological University. Retrieved from https://digitalcommons.mtu.edu/etdr/245

Chicago Manual of Style (16^th Edition):

Salehi, Nasrin. “ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT.” 2016. Doctoral Dissertation, Michigan Technological University. Accessed March 06, 2021. https://digitalcommons.mtu.edu/etdr/245.

MLA Handbook (7^th Edition):

Salehi, Nasrin. “ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT.” 2016. Web. 06 Mar 2021.

Vancouver:

Salehi N. ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT. [Internet] [Doctoral dissertation]. Michigan Technological University; 2016. [cited 2021 Mar 06]. Available from: https://digitalcommons.mtu.edu/etdr/245.

Council of Science Editors:

Salehi N. ENGINEERING ANTIPHAGOCYTIC AND TARGETING THERAPEUTIC CARRIERS FOR CANCER TREATMENT. [Doctoral Dissertation]. Michigan Technological University; 2016. Available from: https://digitalcommons.mtu.edu/etdr/245

University of Minnesota

27. LaRue, Rebecca St. Claire. Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins.

Degree: Comparative and Molecular Biosciences, 2010, University of Minnesota

URL: http://purl.umn.edu/97083

► The mammalian immune system must be dynamic in the face of a diverse and ever-changing array of pathogens. Successful pathogens have evolved to overcome host… (more)

▼ The mammalian immune system must be dynamic in the face of a diverse and ever-changing array of pathogens. Successful pathogens have evolved to overcome host immunity. One of the most successful pathogens in the last century is the human immunodeficiency virus (HIV), which is the etiological agent responsible for the global acquired immune deficiency syndrome (AIDS) epidemic. Currently, one of the most studied host-pathogen interactions is between the cellular anti-retroviral APOBEC3 (A3) proteins and HIV viral infectivity factor (Vif) protein. A3 proteins are cytosine deaminases that primarily inhibit retroviruses and retrotransposons by mutating cytosines to uracils in retroviral DNA during reverse transcription. When HIV Vif is present, it can bind to certain A3 proteins and recruit cellular degradation complexes to target these anti-retroviral proteins for proteasomal degradation. HIV-like viruses (lentiviruses) infect other mammals and are the inspiration for studying A3 proteins in other mammals. The ultimate goal of this comparative study was to gain a better understanding of how the lentiviral Vif protein counteracts host A3 proteins. The first component of this dissertation is dedicated to the process of determining the complete A3 protein repertoires of cow and sheep (representatives of the artiodactyl lineage), which are both infected with a lentiviruses. The second component of this dissertation was to test if these artiodactyl A3 proteins were functional. Cow and sheep A3 proteins demonstrate intrinsic DNA cytosine deaminase activity and localize in cells similar to human A3 proteins. Furthermore, certain cow A3 proteins are capable of restricting HIV and are neutralized in the presence of cattle-specific lentiviral Vif (bovine immunodeficiency virus). The last component of this dissertation, a panel of conserved mammalian A3 proteins were tested to determine if each A3 protein interacts specifically with its species lentiviral Vif protein. It was shown that each representative host A3 protein is degraded in the presence of its species specific lentiviral Vif, suggesting a conserved interaction between mammalian A3 proteins and their species specific lentiviral Vif protein.

Subjects/Keywords: APOBEC3; Comparative; HIV; Immunity; Lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

LaRue, R. S. C. (2010). Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins. (Thesis). University of Minnesota. Retrieved from http://purl.umn.edu/97083

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

LaRue, Rebecca St Claire. “Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins.” 2010. Thesis, University of Minnesota. Accessed March 06, 2021. http://purl.umn.edu/97083.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

LaRue, Rebecca St Claire. “Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins.” 2010. Web. 06 Mar 2021.

Vancouver:

LaRue RSC. Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins. [Internet] [Thesis]. University of Minnesota; 2010. [cited 2021 Mar 06]. Available from: http://purl.umn.edu/97083.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

LaRue RSC. Dynamics of the mammalian APOBEC3 locus and the relationship between mammalian APOBEC3 and Lentiviral Vif proteins. [Thesis]. University of Minnesota; 2010. Available from: http://purl.umn.edu/97083

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Southern California

28. Harboe-Schmidt, Jens Erik. Gene delivery to pulmonary mucosa.

Degree: PhD, Biochemistry & Molecular Biology, 2006, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/21842/rec/2979

► We investigated the use of a replication-defective human immunodeficiency virus-based lentivirus vector pseudotyped with VSV.G for GFP gene transfer to primary rat alveolar epithelial cells… (more)

▼ We investigated the use of a replication-defective human immunodeficiency virus-based lentivirus vector pseudotyped with VSV.G for GFP gene transfer to primary rat alveolar epithelial cells (AEC's). Cells grown on plastic exhibited a dose response with transduction efficiencies of 99% at an MOI's of 50. Importantly, comparison of lentivirus-mediated gene transfer from the apical or basolateral surface of confluent and polarized monolayers of AEC's cultured on semi-permeable supports revealed efficient transduction only when lentivirus was applied apically. Manipulating the tight junctions of the monolayers did not enhance infection, indicating that transduction occurred primarily at the apical membrane. In contrast, differentiated tracheal epithelial cells could only be transduced apically in the presence of EGTA but even then at a much lower overall efficiency (15-fold) than was observed for AEC's suggesting that receptor localization may differ between upper and lower airways.; To determine if these vectors could deliver a functional transgene we set out to study sodium pump activity after gene transfer of the alpha1- or beta1 sodium pump subunits of rat Na+,K+-ATPase. Transduction with Lenti-beta1-EGFP was accompanied by coordinate up-regulation of endogenous alpha1 expression, whereas endogenous beta1 expression was unchanged after transduction with Lenti-alpha1-EGFP. Consistent with these findings, transduction with Lenti-beta1-EGFP led to increases in Na+,K+-ATPase holoenzyme as determined by augmentation of sodium pump activity, and therefore supports the feasibility of lentivirus-mediated gene transfer to augment alveolar fluid clearance.; In vivo studies of lentiviral gene delivery to the distal airways in 4 week old rats by non-invasive, intra-tracheal methods led to transduction efficiencies of up to 21% at 2x108 IU. Gene expression in vivo declined more than 5 fold between day 4 and day 25, and was reduced to background levels at day 50. Delivery of 5x107 IU led to infection of 19.6% macrophages, 3.4% AT1 cells and 3.5% AT2 cells suggesting that macrophages were more susceptible to viral infection. However, pulmonary macrophages represent a minor population of airway cells. We furthermore transduced rats intra-tracheally with lentivirus expressing mIL-4 and were able to detect expression in blood plasma (440 pg mIL-4/ml) for up to 28 days before levels were no longer significant. Advisors/Committee Members: Kedes, Larry (Committee Chair), Frenkel, Baruch (Committee Member), Kasahara, Noriyuki (Committee Member).

Subjects/Keywords: gene; delivery; lentivirus; pulmonary; mucosa

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harboe-Schmidt, J. E. (2006). Gene delivery to pulmonary mucosa. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/21842/rec/2979

Chicago Manual of Style (16^th Edition):

Harboe-Schmidt, Jens Erik. “Gene delivery to pulmonary mucosa.” 2006. Doctoral Dissertation, University of Southern California. Accessed March 06, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/21842/rec/2979.

MLA Handbook (7^th Edition):

Harboe-Schmidt, Jens Erik. “Gene delivery to pulmonary mucosa.” 2006. Web. 06 Mar 2021.

Vancouver:

Harboe-Schmidt JE. Gene delivery to pulmonary mucosa. [Internet] [Doctoral dissertation]. University of Southern California; 2006. [cited 2021 Mar 06]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/21842/rec/2979.

Council of Science Editors:

Harboe-Schmidt JE. Gene delivery to pulmonary mucosa. [Doctoral Dissertation]. University of Southern California; 2006. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/21842/rec/2979

University of Kentucky

29. Trimby, Christopher Matthew. STRATEGIES FOR TARGETING LENTIVIRAL VECTORS.

Degree: 2011, University of Kentucky

URL: https://uknowledge.uky.edu/gradschool_diss/157

► Lentiviral gene therapy has held great promise for treating a wide range of neurological disorders due to its ability to stably integrate into the genome… (more)

▼ Lentiviral gene therapy has held great promise for treating a wide range of neurological disorders due to its ability to stably integrate into the genome of nondividing cells like neurons, in addition to dividing cells. The nervous system is a complex and highly heterogeneous system, and while a therapeutic intervention may have beneficial effects in one population of cells it may have severe side effects in another. For this reason, specific targeting of lentiviral vectors is crucial for their ultimate utility for research and clinical research use. Two different approaches for focusing the targeting of lentiviral vectors were employed in these studies. The first method involved assessing the effects of vector production strategies on the resulting virus’s tropism both in vivo and in vitro. The changes in vector transduction were determined via flow cytometry on cells in culture and immunohistochemistry following brain injections. Results from these experiments suggest that while the production conditions do impact the vectors efficacy, there is not a distinct effect on their tropism. A unique characteristic of retroviral and lentiviral vectors is their capacity for being pseudotyped, conferring a new tropism on the vector. Native tropisms are generally not specific beyond very broad cell types, which may not be sufficient for all applications. In this case, chimeric targeting molecules can provide an even more refined targeting profile compared to native pseudotypes. The second approach utilizes novel chimeric glycoproteins made from nerve growth factor and the vesicular stomatitis virus glycoprotein. These chimeras are designed to pseudotype lentiviral vectors to target nociceptive sensory neurons for a variety of disorders. While these chimeras were successfully produced as protein, they were misfolded and sequestered in the endoplasmic reticulum and therefore unavailable to produce lentivirus. While neither strategy was completely successful, they do provide interesting information for the design and creation of lentiviral vectors. This research shows that small differences in the steps followed as part of a lentivirus production protocol can greatly impact the resulting vectors efficacy. It also shows that while VSV has been used to create chimeric glycoproteins, not all targeting molecules are suitable for this purpose.

Subjects/Keywords: Gene Therapy; Neuroscience; Lentivirus; Chimeric Pseudotyping; Vector production; Medical Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Trimby, C. M. (2011). STRATEGIES FOR TARGETING LENTIVIRAL VECTORS. (Doctoral Dissertation). University of Kentucky. Retrieved from https://uknowledge.uky.edu/gradschool_diss/157

Chicago Manual of Style (16^th Edition):

Trimby, Christopher Matthew. “STRATEGIES FOR TARGETING LENTIVIRAL VECTORS.” 2011. Doctoral Dissertation, University of Kentucky. Accessed March 06, 2021. https://uknowledge.uky.edu/gradschool_diss/157.

MLA Handbook (7^th Edition):

Trimby, Christopher Matthew. “STRATEGIES FOR TARGETING LENTIVIRAL VECTORS.” 2011. Web. 06 Mar 2021.

Vancouver:

Trimby CM. STRATEGIES FOR TARGETING LENTIVIRAL VECTORS. [Internet] [Doctoral dissertation]. University of Kentucky; 2011. [cited 2021 Mar 06]. Available from: https://uknowledge.uky.edu/gradschool_diss/157.

Council of Science Editors:

Trimby CM. STRATEGIES FOR TARGETING LENTIVIRAL VECTORS. [Doctoral Dissertation]. University of Kentucky; 2011. Available from: https://uknowledge.uky.edu/gradschool_diss/157

30. Harrington, Lauriane. The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine.

Degree: Docteur es, Neurosciences, 2015, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2015PA066328

►

Le tabac est consommé par environ un milliard de personnes. D'après l'Organisation Mondiale de la Santé, le tabagisme est la première cause évitable de mortalité… (more)

▼

Le tabac est consommé par environ un milliard de personnes. D'après l'Organisation Mondiale de la Santé, le tabagisme est la première cause évitable de mortalité dans le monde, provocant six millions de morts par an. La nicotine est le composant neuro-actif principal dans le tabac, et exerce ses effets neurologiques via une activation directe des récepteurs nicotiniques de l’acétylcholine (nAChR). Ces récepteurs transmembranaires sont composés de sous-unités alpha, ou alpha plus beta, créant une variété de canaux ioniques ligand-dépendants activés par le neurotransmetteur ACh. Les études génétiques chez l’homme ont mis en évidence des variants dans le cluster génomique CHRNA5-CHRNA3-CHRNB4, codant pour les sous-unités α5, α3 et β4, comme facteurs influençant le tabagisme. Cette thèse a étudié le rôle des nAChRs contenant la sous-unité β4 (β4*) dans l’addiction à la nicotine. En collaboration, nous avons montré que les souris déficientes pour la sous-unité β4 (β4 KO), sont moins sensibles aux effets récompensant et aversifs de la nicotine. En générant un lentivirus exprimant la séquence murine d'ADN complémentaire de β4, j’ai pu restaurer son expression dans des régions d’intérêt du cerveau, sur un fond génétique β4KO. Ceci a permis de mettre en évidence le rôle du réseau habénulo-interpedonculaire dans la contribution des β4* nAChRs à la consommation de nicotine. Ceci a également démontré le rôle modulateur de ces récepteurs dans les réponses de la voie mésolimbique à la nicotine, voie centrale dans l'effet renforçant des drogues.

Tobacco is consumed by an estimated 1 billion people world-wide. The World Health Organization names tobacco consumption the primary cause of preventable morbidity and mortality, causing six million deaths per year. Nicotine is the principal neuro-active compound in tobacco, and exerts neurological effects by binding to nicotinic acetylcholine receptors (nAChRs). These transmembrane receptors are composed of alpha or alpha plus beta subunits, forming a diverse variety of ligand-gated ion channels endogenously activated by ACh. Human genetic studies have highlighted variants in the CHRNA5-CHRNA3-CHRNB4 genomic cluster, coding for subunits α5, α3 and β4, as altering smoking behaviours. The present thesis investigated the role of β4-containing (β4*) nAChRs in nicotine addiction. In collaboration, we showed that β4 knockout (KO) mice are less sensitive to nicotine reward and nicotine aversion. Generating a lentivirus for the expression of mouse β4 nAChR subunit complementary DNA, I was able to restore receptor expression to brain regions of interest on a KO background, locating the role of β4* nAChR in nicotine reward and aversion to the habenulo-interpedunular pathway. This also demonstrated the receptor’s modulation of nicotinic responses of the mesolimbic system, central hub of drug reinforcement.

Advisors/Committee Members: Maskos, Uwe (thesis director).

Subjects/Keywords: Nicotine; Récompense; Aversif; Lentivirus; Récepteurs; Acétylcholine; Nicotine; Receptors; 616.865

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harrington, L. (2015). The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2015PA066328

Chicago Manual of Style (16^th Edition):

Harrington, Lauriane. “The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine.” 2015. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed March 06, 2021. http://www.theses.fr/2015PA066328.

MLA Handbook (7^th Edition):

Harrington, Lauriane. “The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine.” 2015. Web. 06 Mar 2021.

Vancouver:

Harrington L. The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. [cited 2021 Mar 06]. Available from: http://www.theses.fr/2015PA066328.

Council of Science Editors:

Harrington L. The role of β4-containing nicotinic acetylcholine receptors in nicotine addiction : Rôle des récepteurs nicotiniques de l’acétylcholine contenant la sous-unité β4 dans l’addiction à la nicotine. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. Available from: http://www.theses.fr/2015PA066328

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