subject:(Gene Therapy)

University of Oxford

1. Antepowicz, Agata. Development of lung and muscle factories to deliver therapeutic monoclonal antibodies.

Degree: PhD, 2018, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:0bffd69b-6324-4edf-af7a-c5344cc70359 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780516

► Monoclonal antibodies (mAbs), which represent the largest market of any protein therapeutic, are used in the treatment of conditions such as cancer and autoimmune diseases,… (more)

▼ Monoclonal antibodies (mAbs), which represent the largest market of any protein therapeutic, are used in the treatment of conditions such as cancer and autoimmune diseases, and prophylaxis of infections. The complexity of manufacture of mAbs translates to a high cost compared with small-molecule drugs, and their use may be restricted as a result. Gene transfer for direct production of mAbs in vivo could offer an alternative to parenteral administration, with the added benefit of easing patient burden caused by repeated injections or infusions. Studies presented in this thesis investigated the possibility of using gene transfer agents for expression of mAbs in the lung lumen and circulation. Using the secreted reporter protein Gaussia luciferase, delivery of the lentiviral vector recombinant simian immunodeficiency virus, pseudotyped with F and HN proteins from Sendai virus (rSIV.F/HN) for targeting of pulmonary epithelium, was identified as an efficient means of gene transfer to the murine lung, with transgene expression in the lung lumen lasting for at least 12 months in BALB/c mice. The recombinant adeno-associated viral vector serotype 8 (rAAV2/8) injected into the muscle directed robust expression of the reporter protein into the circulation and lung lumen of mice for at least 12 months. Two model applications were used to assess the effectiveness of these vectors for mAb gene transfer: respiratory syncytial virus (RSV) infection and rheumatoid arthritis. Both rSIV.F/HN and rAAV2/8 vectors expressing the anti-RSV mAb palivizumab protected mice from weight loss upon RSV infection. Recombinant AAV2/8 delivered intramuscularly was also used to express the anti-tumour necrosis factor alpha (TNFa) biologics infliximab and etanercept for at least 6 months and 56 days, respectively. Due to the immunosuppressive nature of TNFα antagonists, constitutive expression is undesirable and small molecule-assisted shutoff (SMASh) was investigated as a possible method of regulation of etanercept production. In conclusion, viral vectormediated mAb gene transfer to the muscle and lung could be a feasible alternative to parenteral administration provided that an effective method of regulation of expression following vector delivery can be developed.

Subjects/Keywords: Gene therapy

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APA (6^th Edition):

Antepowicz, A. (2018). Development of lung and muscle factories to deliver therapeutic monoclonal antibodies. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:0bffd69b-6324-4edf-af7a-c5344cc70359 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780516

Chicago Manual of Style (16^th Edition):

Antepowicz, Agata. “Development of lung and muscle factories to deliver therapeutic monoclonal antibodies.” 2018. Doctoral Dissertation, University of Oxford. Accessed January 21, 2021. http://ora.ox.ac.uk/objects/uuid:0bffd69b-6324-4edf-af7a-c5344cc70359 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780516.

MLA Handbook (7^th Edition):

Antepowicz, Agata. “Development of lung and muscle factories to deliver therapeutic monoclonal antibodies.” 2018. Web. 21 Jan 2021.

Vancouver:

Antepowicz A. Development of lung and muscle factories to deliver therapeutic monoclonal antibodies. [Internet] [Doctoral dissertation]. University of Oxford; 2018. [cited 2021 Jan 21]. Available from: http://ora.ox.ac.uk/objects/uuid:0bffd69b-6324-4edf-af7a-c5344cc70359 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780516.

Council of Science Editors:

Antepowicz A. Development of lung and muscle factories to deliver therapeutic monoclonal antibodies. [Doctoral Dissertation]. University of Oxford; 2018. Available from: http://ora.ox.ac.uk/objects/uuid:0bffd69b-6324-4edf-af7a-c5344cc70359 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780516

University of Hawaii – Manoa

2. Anderson, Cynthia Dawn. Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy.

Degree: 2015, University of Hawaii – Manoa

URL: http://hdl.handle.net/10125/100285

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Ph.D. University of Hawaii at Manoa 2014.

The goal of this research was to identify an improved delivery system and vectors for noninvasive gene therapy… (more)

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Ph.D. University of Hawaii at Manoa 2014.

The goal of this research was to identify an improved delivery system and vectors for noninvasive gene therapy of Hemophilia B. Ultrasound Targeted Microbubble Destruction (UTMD) is a platform technology that can deliver geneexpression vectors bound to the shells of lipid microbubbles to organs accessible to ultrasound. In UTMD, the DNA-loaded microbubbles are injected intravenously and are disrupted at the target organ by acoustic cavitation at a resonant frequency of the bubbles, resulting in delivery of expression plasmids to the target organ. Our aim was to apply UTMD to the hepatic delivery of conventional (pcDNA3), piggyBac (pmGENIE) and Sleeping Beauty (SB100x) transposon-based, and minicircle (MC) DNA vectors. We measured reporter and human blood coagulation factor IX transgene expression in the mouse liver and plasma driven by constitutive and tissue-specific promoters. In vitro we demonstrated a ten-fold increase in the level of reporter expression in HEK293 cells after transfection with a piggyBac transposase system over three weeks. In C57Bl/6 mice, we first compared pmGENIE2-luciferase to pcDNA3-luciferase, and observed UTMD-mediated liver-specific expression of pmGENIE2 for an average of 24 days (n=12), compared to 4 days with the pcDNA3 (n=7) (p=0.037). Expression of the reporter constructs was initially predominately located proximal to blood vessels while expression past three days was more evenly distributed through the parenchyma of the liver. We also used nonrestrictive linear amplification mediated (nrLAM) PCR to evaluate the genomic integration sites of the pmGENIE reporter vectors in vitro and in vivo. Chromosomal integration sites were randomly distributed in genomic DNA samples isolated from mouse 3T3 cells transfected with pmGENIE3-eGFP in vitro but were predominately targeted to specific chromosomes in livers from C57BL/6 mice transfected with pmGENIE3-luc (n=13) in vivo. Thus, the UTMD delivery of transposon-based vectors has revealed an unexpected tropism for certain murine chromosomal sites in vivo that is not seen in vitro. We delivered various reporter constructs to the liver by UTMD and compared reporter expression levels and hepatic localization over two weeks. We initially observed robust transgene levels from all vectors, however, the intensity of expression remained 10 to 1000-fold stronger in mice from the pmGENIE3-luc and liver-specific pZY53-luc treatments compared to pcDNA3, SB100X, or minicircle constructs. The greatest hepatic specificity of transgene expression was observed for the alpha1 antitrypsin promoter-driven pZY53-luc, which supports the use of vectors with tissue-specific promoters to further enhance UTMD site-specificity. We also evaluated these vectors with liverspecific promoters and the human factor IX (FIX) gene in HepG2 cells and in C57Bl/6 mice. The optimal hFIX vectors (pZY53-hFIX and pmGENIE3-hFIX) were delivered to the livers of FIX deficient (-/-) mice to determine whether we could ameliorate the…

Subjects/Keywords: gene; therapy

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APA (6^th Edition):

Anderson, C. D. (2015). Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy. (Thesis). University of Hawaii – Manoa. Retrieved from http://hdl.handle.net/10125/100285

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):

Anderson, Cynthia Dawn. “Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy.” 2015. Thesis, University of Hawaii – Manoa. Accessed January 21, 2021. http://hdl.handle.net/10125/100285.

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

MLA Handbook (7^th Edition):

Anderson, Cynthia Dawn. “Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy.” 2015. Web. 21 Jan 2021.

Vancouver:

Anderson CD. Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy. [Internet] [Thesis]. University of Hawaii – Manoa; 2015. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10125/100285.

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

Council of Science Editors:

Anderson CD. Nonviral vector strategies for ultrasound targeted microbubble destruction-mediated hepatic gene therapy. [Thesis]. University of Hawaii – Manoa; 2015. Available from: http://hdl.handle.net/10125/100285

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

University of Texas Southwestern Medical Center

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

Degree: 2011, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/837

► 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 (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 January 21, 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. 21 Jan 2021.

Vancouver:

Ellis BL. Improving Viral Vectors for Gene Targeting in Gene Therapy. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2011. [cited 2021 Jan 21]. 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

Rutgers University

4. FENG, XING, 1987-. Roles of SETD4 in radiation sensitivity and tumorigenesis.

Degree: PhD, Pharmacology, Cellular and Molecular, 2018, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/

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The SET domain protein methyltransferases play a critical role in histone modifications and global epigenetic regulations. Recent evidence suggests that some SET domain proteins may… (more)

Subjects/Keywords: Cancer – Gene therapy

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APA (6^th Edition):

FENG, XING, 1. (2018). Roles of SETD4 in radiation sensitivity and tumorigenesis. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/59084/

Chicago Manual of Style (16^th Edition):

FENG, XING, 1987-. “Roles of SETD4 in radiation sensitivity and tumorigenesis.” 2018. Doctoral Dissertation, Rutgers University. Accessed January 21, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/59084/.

MLA Handbook (7^th Edition):

FENG, XING, 1987-. “Roles of SETD4 in radiation sensitivity and tumorigenesis.” 2018. Web. 21 Jan 2021.

Vancouver:

FENG, XING 1. Roles of SETD4 in radiation sensitivity and tumorigenesis. [Internet] [Doctoral dissertation]. Rutgers University; 2018. [cited 2021 Jan 21]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/.

Council of Science Editors:

FENG, XING 1. Roles of SETD4 in radiation sensitivity and tumorigenesis. [Doctoral Dissertation]. Rutgers University; 2018. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/59084/

University of Texas Southwestern Medical Center

5. Checketts, Joshua Allen. Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells.

Degree: 2013, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/1727

► Gene therapy is the ability to correct diseases at the DNA level and has long been a goal of science and medicine. The earliest gene… (more)

▼ Gene therapy is the ability to correct diseases at the DNA level and has long been a goal of science and medicine. The earliest gene therapy clinical trial was for a patient with severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency. Initial trials looked promising and the technique was extended to other forms of primary immunodeficiency. Unfortunately, some of the patients enrolled in these trials using retroviral vectors to carry replacement genes resulted in insertional oncogenesis. To avoid the insertional oncogenesis caused by random integration into the genome, we postulated that targeted insertion of the gene of interest through homologous recombination would prove to be a safer alternative to random viral insertion of a gene. To this end, we developed several pairs of TAL effector nucleases (TALENs) designed to target exon 1 of ADA. These TALENs function as dimers, and each pair creates a different targeted double strand break near the start site of the ADA gene. The most effective pair induces a DNA double strand break immediately preceding the ADA start codon. Targeted activity of these TALENs was measured through determining the percent of alleles that undergo mutagenic non-homologous end joining upon exposure to the TALENs, with up to 14% of alleles undergoing such mutations. In order to stimulate gene targeting at the ADA locus in human cells, these TALENs were nucleofected into the cells as plasmid DNA, along with a donor plasmid that contains the DNA to be inserted flanked by 800bp arms of homology to the cut site. These TALENs were able to stimulate site-specific integration of the desired fragment at rates of up to 10% in human cell lines. Successful targeted gene insertion was verified through maintained fluorescence, western blots, and sequencing of the targeted alleles through PCR amplification. We demonstrated the ability to enrich for targeted cells through the expression of a selectable marker within the DNA cassette integrated at the ADA locus. In addition to the editing of cell lines, we showed successful stimulation of gene targeting in patient-derived fibroblasts in 1.5% of cells. We demonstrated the feasibility of using the ADA locus as a safe harbor through the targeted insertion of three therapeutically interesting genes. Finally, we demonstrated the successful targeted gene insertion in human CD34+ in up to 0.5% of cells treated. The successful targeting of human CD34+ is especially relevant, as these cells will need to undergo gene targeting in order to be therapeutically relevant as a curative therapy for SCID due to ADA deficiency. Advisors/Committee Members: Albanesi, Joseph P., Porteus, Matthew H., Burma, Sandeep, Abrams, John M., Sternweis, Paul C..

Subjects/Keywords: Gene Therapy; Gene Targeting; Severe Combined Immunodeficiency

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APA (6^th Edition):

Checketts, J. A. (2013). Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1727

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):

Checketts, Joshua Allen. “Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed January 21, 2021. http://hdl.handle.net/2152.5/1727.

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

MLA Handbook (7^th Edition):

Checketts, Joshua Allen. “Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells.” 2013. Web. 21 Jan 2021.

Vancouver:

Checketts JA. Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/2152.5/1727.

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

Council of Science Editors:

Checketts JA. Nuclease-Mediated Targeted Gene Insertion at the Adenosine Deaminase Locus in Primary Cells. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1727

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

University of Rochester

6. Badding, Melissa. Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer.

Degree: PhD, 2012, University of Rochester

URL: http://hdl.handle.net/1802/25532

► For non-viral gene transfer to be successful, plasmids must cross several barriers. Very little is known about how plasmids overcome the barrier presented by the… (more)

▼ For non-viral gene transfer to be successful, plasmids must cross several barriers. Very little is known about how plasmids overcome the barrier presented by the dense meshwork of the cytoplasm, but our lab and others have demonstrated that plasmids utilize the microtubule network for directed movement to the nucleus. Therefore, I sought to determine the molecular mechanisms behind the intracellular movement of plasmids during gene transfer. We have shown that acetylated microtubules promote greater gene delivery, and hypothesized that by modulating the microtubule network we could enhance plasmid interactions with, and trafficking along, microtubules. Two variations of an in vitro microtubule-binding assay and a live-cell plasmid immunoprecipitation assay demonstrated that plasmids have enhanced interactions with highly acetylated microtubules. Through plasmid microinjections and real-time particle tracking, I found that plasmids also have greater net rates of movement in cells with high levels of acetylated microtubules. We also know that plasmids do not directly interact with microtubules and therefore require adapter molecules, but the identity of these had been unknown. Two approaches were used to examine this; both utilizing a live-cell plasmid pull-down assay to isolate plasmid-protein complexes that form during transfection. The first set of experiments show that the cyclic AMP response element binding protein (CREB) permits enhanced plasmid interactions with microtubules and greater cytoplasmic transport. The second set of experiments used mass spectrometry to identify specific proteins that complex with plasmids during transfection. I found many of the proteins hypothesized to play a role in plasmid trafficking to be present. The significance of some of the identified nuclear shuttling proteins in plasmid trafficking and nuclear import was determined using siRNAmediated knockdowns, plasmid microinjections, and particle tracking analysis. I found that some of the identified proteins play an active role not only in nuclear translocation, but also in cytoplasmic trafficking, while others passively bind the complex without contributing to cytoplasmic movement. Taken together, these findings will provide a foundation for uncovering how plasmids move within the cell and how these processes can be exploited to enhance gene therapy.

Subjects/Keywords: Gene Therapy; Trafficking; Nuclear Import

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APA (6^th Edition):

Badding, M. (2012). Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/25532

Chicago Manual of Style (16^th Edition):

Badding, Melissa. “Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer.” 2012. Doctoral Dissertation, University of Rochester. Accessed January 21, 2021. http://hdl.handle.net/1802/25532.

MLA Handbook (7^th Edition):

Badding, Melissa. “Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer.” 2012. Web. 21 Jan 2021.

Vancouver:

Badding M. Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer. [Internet] [Doctoral dissertation]. University of Rochester; 2012. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1802/25532.

Council of Science Editors:

Badding M. Cytoplasmic Factors that Impact Intracellular Plasmid Trafficking During Gene Transfer. [Doctoral Dissertation]. University of Rochester; 2012. Available from: http://hdl.handle.net/1802/25532

University of Toronto

7. Berinstein, Elliot. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.

Degree: 2016, University of Toronto

URL: http://hdl.handle.net/1807/90143

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The adoptive transfer of T lymphocytes expressing chimeric antigen receptors (CARs) has become a promising treatment for various cancers. CARs have been shown to redirect… (more)

Subjects/Keywords: Cancer; Gene Therapy; Immunotherapy; 0992

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

APA (6^th Edition):

Berinstein, E. (2016). The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/90143

Chicago Manual of Style (16^th Edition):

Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Masters Thesis, University of Toronto. Accessed January 21, 2021. http://hdl.handle.net/1807/90143.

MLA Handbook (7^th Edition):

Berinstein, Elliot. “The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1.” 2016. Web. 21 Jan 2021.

Vancouver:

Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1807/90143.

Council of Science Editors:

Berinstein E. The Development Of A Novel Chimeric Antigen Receptor Specific For Syndecan-1. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/90143

University of Toronto

8. Scaife, Matthew. Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease.

Degree: 2010, University of Toronto

URL: http://hdl.handle.net/1807/25794

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Lentivirus-mediated gene therapy has curative potential for a variety of disorders, however, insertional oncogenesis still remains a concern. One approach to increase safety of such… (more)

Subjects/Keywords: gene therapy; fabry disease; 0307

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APA (6^th Edition):

Scaife, M. (2010). Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/25794

Chicago Manual of Style (16^th Edition):

Scaife, Matthew. “Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease.” 2010. Masters Thesis, University of Toronto. Accessed January 21, 2021. http://hdl.handle.net/1807/25794.

MLA Handbook (7^th Edition):

Scaife, Matthew. “Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease.” 2010. Web. 21 Jan 2021.

Vancouver:

Scaife M. Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease. [Internet] [Masters thesis]. University of Toronto; 2010. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1807/25794.

Council of Science Editors:

Scaife M. Truncated Cell Surface Markers Fused with Mutant Human Tmpk: Versatile Cell Fate Control Safety Cassettes for Lentiviral Vector Mediated Correction of Fabry Disease. [Masters Thesis]. University of Toronto; 2010. Available from: http://hdl.handle.net/1807/25794

Boston University

9. Chammas, Chantal. Gene therapy as a viable therapeutic approach for Parkinson's disease.

Degree: MS, Medical Sciences, 2019, Boston University

URL: http://hdl.handle.net/2144/36248

► Parkinson’s Disease (PD) is a neurological disorder affecting the basal ganglia in which the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc)… (more)

Subjects/Keywords: Neurosciences; Gene therapy; Parkinson's disease

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

APA (6^th Edition):

Chammas, C. (2019). Gene therapy as a viable therapeutic approach for Parkinson's disease. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/36248

Chicago Manual of Style (16^th Edition):

Chammas, Chantal. “Gene therapy as a viable therapeutic approach for Parkinson's disease.” 2019. Masters Thesis, Boston University. Accessed January 21, 2021. http://hdl.handle.net/2144/36248.

MLA Handbook (7^th Edition):

Chammas, Chantal. “Gene therapy as a viable therapeutic approach for Parkinson's disease.” 2019. Web. 21 Jan 2021.

Vancouver:

Chammas C. Gene therapy as a viable therapeutic approach for Parkinson's disease. [Internet] [Masters thesis]. Boston University; 2019. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/2144/36248.

Council of Science Editors:

Chammas C. Gene therapy as a viable therapeutic approach for Parkinson's disease. [Masters Thesis]. Boston University; 2019. Available from: http://hdl.handle.net/2144/36248

University of Manitoba

10. Wang, Xiaoxia. Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.

Degree: Medical Microbiology, 2012, University of Manitoba

URL: http://hdl.handle.net/1993/23226

► Currently, the HIV pandemic remains a major global health challenge. In order to effectively control and cure HIV-1 infection, it is necessary to perform greater… (more)

▼ Currently, the HIV pandemic remains a major global health challenge. In order to effectively control and cure HIV-1 infection, it is necessary to perform greater research on host-HIV interactions and develop novel preventive and therapeutic approaches. The human cytidine deaminase APOBEC3G (A3G) is the first identified host restriction factor, which can serve as an initial line of defense against HIV-1 by inducing lethal mutations on proviral DNA and disrupting viral reverse transcription and integration. In order to better understand the action of A3G on HIV-1 replication, my study was focused on characterizing the interplay between A3G and HIV-1 reverse transcriptase (RT). The results indicated that A3G directly bound to RT, which contributed to A3G-mediated inhibition of viral reverse transcription. Overexpression of the RT-binding polypeptide A3G65-132 was able to disrupt wild-type A3G and RT interaction, consequently attenuating the anti-HIV effect of A3G on HIV replication. While the potent antiviral activities of A3G make it an attractive candidate for gene therapy, the actions of A3G can be counteracted by HIV-1 Vif during wild-type HIV infection. In order to overcome Vif-mediated blockage and maximize the antiviral activity of A3G, this protein was fused with a virus-targeting polypeptide (R88) derived from HIV-1 Vpr, and various mutations were then introduced into R88-A3G fusion protein. Results showed that Vif binding mutants R88-A3GD128K and R88-A3GP129A exhibited very potent antiviral activity, and blocked HIV-1 replication in a CD4+ T lymphocyte cell line as well as human primary cells. In an attempt to further determine their potential against drug resistant viruses and viruses produced from latently infected cells, R88-A3GD128K was chosen and delivered by an inducible lentiviral vector system. Expression of R88-A3GD128K in actively and latently HIV-1 infected cells was shown to be able to inhibit the replication of both drug sensitive and resistant strains of HIV-1. In conclusion, this thesis has demonstrated one of the mechanisms that how A3G can disrupt HIV-1 reverse transcription. Meanwhile, an A3G-based anti-HIV-1 strategy has been developed, which provides a proof-of-principle for a new gene therapy approach against this deadly virus. Advisors/Committee Members: Yao, Xiao-Jian (Medical Microbiology) (supervisor), Ball, Blake T (Medical Microbiology) Li, Yan (Medical Microbiology) Kung, Sam (Immunology) Liang, Chen (McGill University) (examiningcommittee).

Subjects/Keywords: APOBEC3G; HIV-1; gene therapy

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APA (6^th Edition):

Wang, X. (2012). Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/23226

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):

Wang, Xiaoxia. “Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.” 2012. Thesis, University of Manitoba. Accessed January 21, 2021. http://hdl.handle.net/1993/23226.

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

MLA Handbook (7^th Edition):

Wang, Xiaoxia. “Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach.” 2012. Web. 21 Jan 2021.

Vancouver:

Wang X. Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. [Internet] [Thesis]. University of Manitoba; 2012. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1993/23226.

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

Council of Science Editors:

Wang X. Molecular studies on the action of APOBEC3G against HIV-1 and development of an APOBEC-based anti-HIV approach. [Thesis]. University of Manitoba; 2012. Available from: http://hdl.handle.net/1993/23226

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

University of Adelaide

11. 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 (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 January 21, 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. 21 Jan 2021.

Vancouver:

Kremer KL. Cystic Fibrosis gene therapy: methods for the optimisation of CFTR gene delivery. [Internet] [Thesis]. University of Adelaide; 2010. [cited 2021 Jan 21]. 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

University of Oxford

12. Orlans, Harry. Developing treatments for rhodopsin-related dominant retinitis pigmentosa.

Degree: PhD, 2019, University of Oxford

URL: http://ora.ox.ac.uk/objects/uuid:82b393a5-aeb5-498c-9d30-d5e988d651e0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780804

► Mutations in the rhodopsin gene are one of the most common causes of autosomal dominant retinitis pigmentosa (ADRP) and there is at present no treatment… (more)

Subjects/Keywords: Gene Therapy; Ophthalmology; Genetics

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APA (6^th Edition):

Orlans, H. (2019). Developing treatments for rhodopsin-related dominant retinitis pigmentosa. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:82b393a5-aeb5-498c-9d30-d5e988d651e0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780804

Chicago Manual of Style (16^th Edition):

Orlans, Harry. “Developing treatments for rhodopsin-related dominant retinitis pigmentosa.” 2019. Doctoral Dissertation, University of Oxford. Accessed January 21, 2021. http://ora.ox.ac.uk/objects/uuid:82b393a5-aeb5-498c-9d30-d5e988d651e0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780804.

MLA Handbook (7^th Edition):

Orlans, Harry. “Developing treatments for rhodopsin-related dominant retinitis pigmentosa.” 2019. Web. 21 Jan 2021.

Vancouver:

Orlans H. Developing treatments for rhodopsin-related dominant retinitis pigmentosa. [Internet] [Doctoral dissertation]. University of Oxford; 2019. [cited 2021 Jan 21]. Available from: http://ora.ox.ac.uk/objects/uuid:82b393a5-aeb5-498c-9d30-d5e988d651e0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780804.

Council of Science Editors:

Orlans H. Developing treatments for rhodopsin-related dominant retinitis pigmentosa. [Doctoral Dissertation]. University of Oxford; 2019. Available from: http://ora.ox.ac.uk/objects/uuid:82b393a5-aeb5-498c-9d30-d5e988d651e0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780804

Rice University

13. Robinson, Tawana M. Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance.

Degree: PhD, Natural Sciences, 2019, Rice University

URL: http://hdl.handle.net/1911/106024

► Adeno-associated virus (AAV) has earned significant attention as a safe and efficient gene therapy tool. AAV has been used in over 100 clinical trials to… (more)

Subjects/Keywords: Adeno-associated; virus; gene therapy

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APA (6^th Edition):

Robinson, T. M. (2019). Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/106024

Chicago Manual of Style (16^th Edition):

Robinson, Tawana M. “Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance.” 2019. Doctoral Dissertation, Rice University. Accessed January 21, 2021. http://hdl.handle.net/1911/106024.

MLA Handbook (7^th Edition):

Robinson, Tawana M. “Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance.” 2019. Web. 21 Jan 2021.

Vancouver:

Robinson TM. Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance. [Internet] [Doctoral dissertation]. Rice University; 2019. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1911/106024.

Council of Science Editors:

Robinson TM. Engineering Adeno-Associated Virus for Protease Targeted Gene Therapy and Immune Avoidance. [Doctoral Dissertation]. Rice University; 2019. Available from: http://hdl.handle.net/1911/106024

14. Pouw, Nadine. Towards effective TCR gene therapy: preclinical requirements.

Degree: 2010, Erasmus University Medical Center

URL: http://hdl.handle.net/1765/38592

Subjects/Keywords: gene therapy

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

APA (6^th Edition):

Pouw, N. (2010). Towards effective TCR gene therapy: preclinical requirements. (Doctoral Dissertation). Erasmus University Medical Center. Retrieved from http://hdl.handle.net/1765/38592

Chicago Manual of Style (16^th Edition):

Pouw, Nadine. “Towards effective TCR gene therapy: preclinical requirements.” 2010. Doctoral Dissertation, Erasmus University Medical Center. Accessed January 21, 2021. http://hdl.handle.net/1765/38592.

MLA Handbook (7^th Edition):

Pouw, Nadine. “Towards effective TCR gene therapy: preclinical requirements.” 2010. Web. 21 Jan 2021.

Vancouver:

Pouw N. Towards effective TCR gene therapy: preclinical requirements. [Internet] [Doctoral dissertation]. Erasmus University Medical Center; 2010. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1765/38592.

Council of Science Editors:

Pouw N. Towards effective TCR gene therapy: preclinical requirements. [Doctoral Dissertation]. Erasmus University Medical Center; 2010. Available from: http://hdl.handle.net/1765/38592

University of Missouri – Columbia

15. Korampally, Madhuri. Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection.

Degree: 2014, University of Missouri – Columbia

URL: http://hdl.handle.net/10355/45908

► [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Shock waves have potential applications in many areas such as in geology, seismological techniques, and… (more)

▼ [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Shock waves have potential applications in many areas such as in geology, seismological techniques, and biomedical applications. Specifically in biomedical field, shock waves can be used to permeabilize cells, allowing a wide variety of particles to penetrate the cell membrane for gene therapy or drug delivery applications. Recently, nanothermite composition consisting of fuel and oxidizer nanoparticles was shown to propagate at velocities in the same range as the heavy-metal azides including metallic azides and fulminates, however, the destructive forces associated with the later materials is not exhibited. Large range of tunability can be achieved by modifying the nanothermite compositions by adding polymers or other nanoscale energetic materials. Also, these nanothermites can be integrated with MEMS based systems owing to their low critical combustion diameters and high energy densities. The present research describes the characterization of different nanothermite composites and the fabrication of a shockwave reaction actuator incorporating MEMS based micro-devices. The actuator was specifically designed for experimenting with biological samples and testing particle delivery and transfection capability which are key aspects in gene therapy. Each actuator component was first characterized to study its effect on the shockwave generation and propagation. The actuator demonstrates the delivery of 59 to 77 kDa FITC-Dextran into chicken cardiomyocytes with cytoplasmic delivery efficiency greater than 90 %, maximum intranuclear delivery efficiency of 84 %, and cell survival rates exceeding 95 % in minimum operating pressure conditions. In addition to the superior delivery efficiencies and cell survival, the results also indicate the ability to control the level of particle delivery. Tunable nanothermite reactions enable versatile pressure generating characteristics which can extend the technology to a spectrum of molecular delivery applications. Advisors/Committee Members: Gangopadhyay, Shubhra (advisor).

Subjects/Keywords: Shock waves; Gene therapy; Nanoparticles

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

APA (6^th Edition):

Korampally, M. (2014). Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection. (Thesis). University of Missouri – Columbia. Retrieved from http://hdl.handle.net/10355/45908

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):

Korampally, Madhuri. “Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection.” 2014. Thesis, University of Missouri – Columbia. Accessed January 21, 2021. http://hdl.handle.net/10355/45908.

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

MLA Handbook (7^th Edition):

Korampally, Madhuri. “Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection.” 2014. Web. 21 Jan 2021.

Vancouver:

Korampally M. Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection. [Internet] [Thesis]. University of Missouri – Columbia; 2014. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10355/45908.

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

Council of Science Editors:

Korampally M. Fabrication and characterization of micro-chip based shockwave generator for particle delivery and cell transfection. [Thesis]. University of Missouri – Columbia; 2014. Available from: http://hdl.handle.net/10355/45908

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

University of Minnesota

16. Ou, Li. Molecular Therapy and Gene Therapy for Hurler Syndrome.

Degree: PhD, Molecular, Cellular, Developmental Biology and Genetics, 2015, University of Minnesota

URL: http://hdl.handle.net/11299/175288

► Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease which leads to systemic disease, including progressive neurodegeneration, mental retardation and death before the age… (more)

▼ Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease which leads to systemic disease, including progressive neurodegeneration, mental retardation and death before the age of 10 years. MPS I results from deficiency of α-L-iduronidase (IDUA) and subsequent accumulation of glycosaminoglycans (GAG). IDUA enzyme acitivity is an essential assessment for research and diagnostic testing of MPS I disease. Due to different parameters (reaction time, temperature and substrate concentration) used by different labs, the enzyme levels of a certain sample varied. To solve the inconsistency of IDUA enzyme assays in this field, a standardized protocol of IDUA enzyme assay was established through adjustment by Michaelis-Menten equation (Chaper 1). In clinical practice, MPS I disease is treated by enzyme replacement therapy (ERT) and bone marrow transplantation (BMT). Clinical ERT with intravenous IDUA reverses some aspects of MPS I disease and ameliorates others. However, neurologic benefits are thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from reaching the central nervous system (CNS). To address this question, high-dose IDUA (11.6 mg/kg, once per week, 4 weeks) was administered to adult MPS I mice. IDUA enzyme activity in cortex of injected mice increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were reduced by 63% of that from untreated MPS I mice (p<0.05). Water T-maze tests showed that the learning abnormality in MPS I mice was surprisingly reduced (p<0.0001). These results demonstrated the efficacy of high dose ERT in treating neurological diseases in MPS I mice (Chapter 2). Previous study in our lab showed that a single administration of lentiviral vector in neonatal MPS I mice can achieve significant metabolic correction and neurological improvements. To further improve the efficacy of lentiviral gene therapy, a total of 9 constructs were designed by codon optimization, and different combination of promoters and enhancers. The transgene expression of these 10 constructs was compared after transfection into HEK 293FT cells, and 5 constructs with the highest IDUA expression were identified (Chapter 4). These results pave the way for developing a directly applicable clinical trial of human lentiviral gene therapy for MPS I disease, and also provide evidence for vector design for treating other lysosomal diseases.

Subjects/Keywords: gene therapy; Hurler syndrome

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

APA (6^th Edition):

Ou, L. (2015). Molecular Therapy and Gene Therapy for Hurler Syndrome. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/175288

Chicago Manual of Style (16^th Edition):

Ou, Li. “Molecular Therapy and Gene Therapy for Hurler Syndrome.” 2015. Doctoral Dissertation, University of Minnesota. Accessed January 21, 2021. http://hdl.handle.net/11299/175288.

MLA Handbook (7^th Edition):

Ou, Li. “Molecular Therapy and Gene Therapy for Hurler Syndrome.” 2015. Web. 21 Jan 2021.

Vancouver:

Ou L. Molecular Therapy and Gene Therapy for Hurler Syndrome. [Internet] [Doctoral dissertation]. University of Minnesota; 2015. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/11299/175288.

Council of Science Editors:

Ou L. Molecular Therapy and Gene Therapy for Hurler Syndrome. [Doctoral Dissertation]. University of Minnesota; 2015. Available from: http://hdl.handle.net/11299/175288

17. Mastorakos, Panagiotis. Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος.

Degree: 2017, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/42189

►

Gene therapy is a novel tool for treating central nervous system diseases with unfavorable prognosis. Despite the promising results of multiple clinical studies, the limited… (more)

▼

Gene therapy is a novel tool for treating central nervous system diseases with unfavorable prognosis. Despite the promising results of multiple clinical studies, the limited distribution of gene delivery, the reduced expression of the therapeutic gene in the target organ, and the low therapeutic index of some regimens constitute major obstacles. In particular, viral vectors have particular shortcomings attributed to the increased risk of mutagenesis, triggering of a subsequent immune response, limited size of the therapeutic gene, and complexity of scaling production. Nanotechnology offer a safe gene delivery platform devoid of adverse effects associated with virus-based systems. However, to date only a few clinical studies have shown promising results using non-viral gene vectors. This phenomenon is due to the inability of such genes to be evenly distributed in the brain parenchyma and the low rate of gene transfer to the target cells. Important barriers to this process are the blood-brain barrier and the extracellular space, which prevent the accumulation and wide distribution of nanoparticles. Here we constructed synthetic non-viral vectors capable of penetrating and evenly distributing within the brain tissue allowing expression of therapeutic genes in a large number of cells. Administration of these vectors by convection-enhanced delivery into the parenchyma permits further dispersion of the synthetic carriers. We expanded this particular technique to synthesize brain penetrating gene vectors using state-of-the-art biodegradable polymers. Furthermore, we used these non-viral vectors for the effective intracranial administration of therapeutic plasmids against glioblastoma. These vectors widely distribute within the tumor, and thus allow for high levels of therapeutic transgene expression thus significantly improving the therapeutic effect in two aggressive glioblastoma models. Finally, by combining blood-brain barrier opening using focused ultrasound with systemically administered nanoparticles, we developed a non-invasive strategy to achieve safe, highly localized, strong and stable expression of transgenes in the central nervous system.

Η γονιδιακή θεραπεία αποτελεί ένα νέο εργαλείο για την αντιμετώπιση νοσημάτων του κεντρικού νευρικού συστήματος με δυσμενή πρόγνωση. Παρά τα θετικά αποτελέσματα ποικiλων κλινικών μελετών, ο περιορισμένος όγκος κατανομής των γονιδιακών φορέων, η μειωμένη έκφραση του θεραπευτικού γονιδίου στο όργανο στόχο καθώς και ο χαμηλός θεραπευτικός δείκτης ορισμένων θεραπευτικών σχημάτων αποτελούν σημαντικά εμπόδια. Πιο συγκεκριμένα, οι ευρείας χρήσεως ιικοί φορείς παρουσιάζουν ιδιαίτερες δυσκολίες λόγω του αυξημένου κινδύνου μεταλλαξιγένεσης, πυροδότησης επακόλουθης ανοσολογικής αντίδρασης, περιορισμούς ως προς το μέγεθος του θεραπευτικού γονιδίου και δυσκολίες στην αναβάθμιση παραγωγής αυτών. Η νανοτεχνολογία προσφέρει καινοτόμες λύσεις στα προαναφερθέντα προβλήματα συμβάλλοντας στη σχεδίαση ασφαλών γονιδιακών φορέων με ελεγχόμενα και διαμορφώσιμα χαρακτηριστικά. Ωστόσο, μέχρι σήμερα…

Subjects/Keywords: Γονιδιακή θεραπεία; Gene therapy

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

APA (6^th Edition):

Mastorakos, P. (2017). Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/42189

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):

Mastorakos, Panagiotis. “Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος.” 2017. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed January 21, 2021. http://hdl.handle.net/10442/hedi/42189.

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

MLA Handbook (7^th Edition):

Mastorakos, Panagiotis. “Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος.” 2017. Web. 21 Jan 2021.

Vancouver:

Mastorakos P. Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10442/hedi/42189.

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

Council of Science Editors:

Mastorakos P. Γονιδιακή θεραπεία νόσων του κεντρικού νευρικού συστήματος. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. Available from: http://hdl.handle.net/10442/hedi/42189

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

University of Sydney

18. McAllery, Samantha Ann. Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale .

Degree: 2016, University of Sydney

URL: http://hdl.handle.net/2123/16702

► Lentiviral gene therapy has the potential to target HIV-1 reservoirs. However, a major obstacle in effectively targeting the HIV-1 latent reservoir is the lack of… (more)

▼ Lentiviral gene therapy has the potential to target HIV-1 reservoirs. However, a major obstacle in effectively targeting the HIV-1 latent reservoir is the lack of efficient gene delivery that occurs within cells. The viral protein Vpx from the SIVSM/HIV-2 lineage is capable of increasing lentiviral reverse transcription (RTn); by antagonizing the restriction factor SAMHD1. This study aimed to investigate the feasibility of incorporating Vpx into lentiviral vectors. Primary macrophages and dendritic cells were utilised as resting cell models. Firstly, we determined the short and long-term effects post-Vpx exposure. Results revealed Vpx exposure led to increased permissiveness of cells to HIV-1 infection over a period that exceeded two weeks and was associated with lower potency of HIV antiretrovirals that target HIV RT or integration. Secondly, we incorporated Vpx with lentiviral gene therapy approaches that target HIV pre- and post-RTn and determined whether the inclusion of Vpx increased their effectiveness. When Vpx was incorporated into anti-HIV gene therapy constructs, transduction levels were significantly increased. However, increase in gene delivery only translated into an increase in HIV protection with constructs that inhibit pre-RTn phases of the virus life cycle. Thirdly, we utilised proteomics to determine any hidden phenotypes, in macrophages and dendritic cells, post-Vpx exposure, which could affect the usage of Vpx in gene therapy protocols. Significant protein changes were further investigated by generating a panel of THP1 knockdown/overexpression cell lines and examining whether individual changes, similar to SAMHD1 depletion, could increase HIV-1 infection. No detrimental hidden phenotypes were revealed in both macrophages and dendritic cells. Importantly, two knockdown cell lines, CALR and FKBP5, were shown to enhance HIV-1, in the absence of Vpx. In conclusion, this study supports the use of Vpx with gene therapy vectors as a way to overcome the major genetic delivery obstacle presented in resting cells. This effect was the greatest when incorporating anti-HIV constructs that target HIV-1 prior to reverse transcription. Importantly this approach can target cells of the existing HIV-1 latent reservoir or in resting cells that require HIV-1 protection.

Subjects/Keywords: HIV; gene therapy; virology; Vpx

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APA (6^th Edition):

McAllery, S. A. (2016). Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/16702

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):

McAllery, Samantha Ann. “Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale .” 2016. Thesis, University of Sydney. Accessed January 21, 2021. http://hdl.handle.net/2123/16702.

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

MLA Handbook (7^th Edition):

McAllery, Samantha Ann. “Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale .” 2016. Web. 21 Jan 2021.

Vancouver:

McAllery SA. Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale . [Internet] [Thesis]. University of Sydney; 2016. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/2123/16702.

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

Council of Science Editors:

McAllery SA. Investigating the feasibility of incorporating Vpx into lentiviral gene therapy vectors: at a global and targeted scale . [Thesis]. University of Sydney; 2016. Available from: http://hdl.handle.net/2123/16702

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

Rutgers University

19. Demiryurek, Yasir, 1985-. Transport and resealing dynamics of two pulse electroporation mediated molecular delivery.

Degree: MS, Mechanical and Aerospace Engineering, 2014, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/45233/

► Electroporation-mediated molecular delivery is of interest for many drug-delivery and gene-therapy applications. Recent studies have shown that a two-pulse protocol consisting of a short-duration high-voltage… (more)

▼ Electroporation-mediated molecular delivery is of interest for many drug-delivery and gene-therapy applications. Recent studies have shown that a two-pulse protocol consisting of a short-duration high-voltage first pulse followed by a longer, low-voltage second pulse can increase the efficiency of molecular delivery and preserve more cells alive with suitably chosen pulsing parameters. In this work we investigate the effects of the first and second pulses’ field strength and the inter-pulse delay time on the delivery of two different-sized Fluorescein-Dextran conjugates (10 kDa and 70 kDa). A series of two-pulse electroporation experiments were performed on 3T3 mouse fibroblast cells, with an alternating-current first pulse to permeabilize the cell, followed by a direct-current second pulse to electrophoretically deliver the target molecule into the cell. Our results showed that the delivery amounts of Fluorescein-Dextran varies strongly with the first pulse's field strength and target molecule size. By varying the delay times between two pulses, it is shown that the delivered intracellular concentration of Fluorescein-Dextran decreased linearly with the logarithm of delay time. The data also indicate that membrane resealing after electropermeabilization occurs very rapidly, but that a non-negligible fraction of the pores can be reopened by the second pulse for times on the order of 100 s. The role of the second pulses is seen to be more than just electrophoresis, with a minimum threshold field strength required to reopen nano-sized pores or defects remaining from the first pulse. These results suggest that membrane electroporation, sealing, and reporation is a complex process that has both short-term and long-term components, which may in part explain the wide variation in membrane-resealing times reported in the literature. Advisors/Committee Members: Shan, Jerry (chair), Lin, Hao (internal member), Zahn, Jeffrey (outside member), Shreiber, David (outside member).

Subjects/Keywords: Electroporation; Fluorescein; Gene therapy

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APA (6^th Edition):

Demiryurek, Yasir, 1. (2014). Transport and resealing dynamics of two pulse electroporation mediated molecular delivery. (Masters Thesis). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/45233/

Chicago Manual of Style (16^th Edition):

Demiryurek, Yasir, 1985-. “Transport and resealing dynamics of two pulse electroporation mediated molecular delivery.” 2014. Masters Thesis, Rutgers University. Accessed January 21, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/45233/.

MLA Handbook (7^th Edition):

Demiryurek, Yasir, 1985-. “Transport and resealing dynamics of two pulse electroporation mediated molecular delivery.” 2014. Web. 21 Jan 2021.

Vancouver:

Demiryurek, Yasir 1. Transport and resealing dynamics of two pulse electroporation mediated molecular delivery. [Internet] [Masters thesis]. Rutgers University; 2014. [cited 2021 Jan 21]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/45233/.

Council of Science Editors:

Demiryurek, Yasir 1. Transport and resealing dynamics of two pulse electroporation mediated molecular delivery. [Masters Thesis]. Rutgers University; 2014. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/45233/

Rutgers University

20. Karjoo Diarkhan, Zahra, 1980-. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.

Degree: PhD, Pharmaceutical Science, 2015, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/

►

Developing an efficient and safe system for gene delivery is considered the bottleneck of gene therapy, where a successful delivery of the nucleic acid can… (more)

▼

Developing an efficient and safe system for gene delivery is considered the bottleneck of gene therapy, where a successful delivery of the nucleic acid can reverse a defective cellular pathway to normal, eradicate cancer at molecular level or simply make it more susceptible to current chemotherapies. Not only have the intracellular events played a crucial role for obtaining a successful gene delivery, but the interaction of nano-particles with extracellular factors should be studied as well. The goal of this study was to design, produce and optimize a non-viral gene delivery system for targeted delivery of nucleic acid such as reporter genes (e.g., green fluorescent protein) or therapeutic genes (e.g., suicide genes) to cancer cells. The system was designed in a way to be easily customized for different cancer types, still presenting a high level of targeted delivery. The first chapter of this thesis will focus on the concept of gene therapy and current systems used for this modality. Different types of vectors including viral and non-viral polymeric vectors will be discussed briefly and the advantages and disadvantages of each will be mentioned. We also discussed natured inspired biopolymers such as peptides and amino acid based vectors which are the fundamental premise of this study. In chapter II, the concept of suicide gene therapy will be explained. Additionally, the current enzyme/prodrug systems, different methods for delivery of suicide genes will be elaborated. In chapter III and IV, the new nanotechnology platform for targeted delivery of plasmid DNA to HER2-positive ovarian cancer cells and HER2-negative prostate cancer cells will be presented. In chapter III, the method for optimization of nanotechnology platform will be discussed and the features of optimized particles will be presented. Chapter IV explains the modification we introduced to the vectors’ primary structure to customize it for a different cell line. Also another method for optimization of amino-acid based vectors for in vivo delivery will be introduced. In these two chapters, the methods of designing and the efficiency of each vector to fulfill the expected goals as well as their safety will be discussed in details and supportive data will be presented.

Advisors/Committee Members: Hatefi, Arash (chair), Minko, Tamara (internal member), You, Guofeng (internal member), GOW, ANDREW (outside member).

Subjects/Keywords: Gene therapy; Cancer – Treatment; Nanoparticles

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APA (6^th Edition):

Karjoo Diarkhan, Zahra, 1. (2015). Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/46367/

Chicago Manual of Style (16^th Edition):

Karjoo Diarkhan, Zahra, 1980-. “Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.” 2015. Doctoral Dissertation, Rutgers University. Accessed January 21, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/46367/.

MLA Handbook (7^th Edition):

Karjoo Diarkhan, Zahra, 1980-. “Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells.” 2015. Web. 21 Jan 2021.

Vancouver:

Karjoo Diarkhan, Zahra 1. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Jan 21]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/.

Council of Science Editors:

Karjoo Diarkhan, Zahra 1. Customization and optimization of a histone h2a-based vector for targeted gene transfer to cancer cells. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/46367/

California State University – Sacramento

21. 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 January 21, 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. 21 Jan 2021.

Vancouver:

Cicchetto AC. Genetically modified multipotent stromal cells for the treatment of osteoarthritis. [Internet] [Masters thesis]. California State University – Sacramento; 2016. [cited 2021 Jan 21]. 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

Leiden University

22. Vrins, C. Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia.

Degree: 2005, Leiden University

URL: http://hdl.handle.net/1887/632

Subjects/Keywords: Gene therapy; Gene therapy

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APA (6^th Edition):

Vrins, C. (2005). Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia. (Doctoral Dissertation). Leiden University. Retrieved from http://hdl.handle.net/1887/632

Chicago Manual of Style (16^th Edition):

Vrins, C. “Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia.” 2005. Doctoral Dissertation, Leiden University. Accessed January 21, 2021. http://hdl.handle.net/1887/632.

MLA Handbook (7^th Edition):

Vrins, C. “Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia.” 2005. Web. 21 Jan 2021.

Vancouver:

Vrins C. Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia. [Internet] [Doctoral dissertation]. Leiden University; 2005. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1887/632.

Council of Science Editors:

Vrins C. Modulation of gene expression in the liver: towards targeted correction of hyperlipidemia. [Doctoral Dissertation]. Leiden University; 2005. Available from: http://hdl.handle.net/1887/632

23. Kobayashi, Yuji. Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響.

Degree: 博士（医学）, 2017, Niigata University / 新潟大学

URL: http://hdl.handle.net/10191/47583

►

学位の種類: 博士（医学）. 報告番号: 甲第4252号. 学位記番号: 新大院博（医）甲第730号. 学位授与年月日: 平成29年3月23日

Molecular Therapy. Nucleic Acids 5(8) e359 2016

Hydrodynamic gene delivery is a common method for gene transfer… (more)

Subjects/Keywords: gene therapy; hydrodynamic gene delivery; liver fibrosis; MMP13; nonviral gene delivery

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APA (6^th Edition):

Kobayashi, Y. (2017). Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響. (Thesis). Niigata University / 新潟大学. Retrieved from http://hdl.handle.net/10191/47583

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):

Kobayashi, Yuji. “Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響.” 2017. Thesis, Niigata University / 新潟大学. Accessed January 21, 2021. http://hdl.handle.net/10191/47583.

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

MLA Handbook (7^th Edition):

Kobayashi, Yuji. “Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響.” 2017. Web. 21 Jan 2021.

Vancouver:

Kobayashi Y. Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響. [Internet] [Thesis]. Niigata University / 新潟大学; 2017. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10191/47583.

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

Council of Science Editors:

Kobayashi Y. Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery. : 肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響. [Thesis]. Niigata University / 新潟大学; 2017. Available from: http://hdl.handle.net/10191/47583

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

24. Davis, Martin. Gene Editing and Human Flourishing.

Degree: 2020, The Catholic University of America

URL: http://hdl.handle.net/1961/cuislandora:214557

►

The advent of gene editing technology brings with it new ethical challenges. Among these challenges is the question of what kinds of gene editing should… (more)

Subjects/Keywords: Enhancement; Ethics; Gene Editing; Gene Enhancement; Gene Therapy; Human Flourishing

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APA (6^th Edition):

Davis, M. (2020). Gene Editing and Human Flourishing. (Thesis). The Catholic University of America. Retrieved from http://hdl.handle.net/1961/cuislandora:214557

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):

Davis, Martin. “Gene Editing and Human Flourishing.” 2020. Thesis, The Catholic University of America. Accessed January 21, 2021. http://hdl.handle.net/1961/cuislandora:214557.

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

MLA Handbook (7^th Edition):

Davis, Martin. “Gene Editing and Human Flourishing.” 2020. Web. 21 Jan 2021.

Vancouver:

Davis M. Gene Editing and Human Flourishing. [Internet] [Thesis]. The Catholic University of America; 2020. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1961/cuislandora:214557.

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

Council of Science Editors:

Davis M. Gene Editing and Human Flourishing. [Thesis]. The Catholic University of America; 2020. Available from: http://hdl.handle.net/1961/cuislandora:214557

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

Massey University

25. Yang, Tian. Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.

Degree: MSc, Biochemistry, 2013, Massey University

URL: http://hdl.handle.net/10179/4319

► Lentiviral vectors, originally derived from human immunodeficiency virus, provide highly efficient viral gene delivery vehicles. Lentiviral vectors often use a constitutive promoter to drive the… (more)

Subjects/Keywords: Lentiviral vectors; Gene therapy; Gene expression; Gene regulation; Tetracycline; Genetic vectors

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APA (6^th Edition):

Yang, T. (2013). Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. (Masters Thesis). Massey University. Retrieved from http://hdl.handle.net/10179/4319

Chicago Manual of Style (16^th Edition):

Yang, Tian. “Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.” 2013. Masters Thesis, Massey University. Accessed January 21, 2021. http://hdl.handle.net/10179/4319.

MLA Handbook (7^th Edition):

Yang, Tian. “Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.” 2013. Web. 21 Jan 2021.

Vancouver:

Yang T. Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. [Internet] [Masters thesis]. Massey University; 2013. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10179/4319.

Council of Science Editors:

Yang T. Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. [Masters Thesis]. Massey University; 2013. Available from: http://hdl.handle.net/10179/4319

University College Cork

26. Sadadcharam, Mira. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.

Degree: 2015, University College Cork

URL: http://hdl.handle.net/10468/3484

► Cancer is a global phenomenon transcending the boundaries of age, race, geography and socioeconomic background. As our understanding of cancer cell biology has improved, we… (more)

▼ Cancer is a global phenomenon transcending the boundaries of age, race, geography and socioeconomic background. As our understanding of cancer cell biology has improved, we have developed a growing appreciation of cancer as a systemic disease. However, our improved understanding has been matched by cancer cell evolution and it is becoming increasingly clear that the future of anti-cancer therapies lies in a multi-modal approach. In this thesis, we adopted a “three-legged stool” approach to anti-cancer therapy. The first leg encompasses primary tumour ablation. We developed the EndoVe device, enabling endoscopic electroporation of gastrointestinal tissues and tumours. We conducted a pre-clinical evaluation of the EndoVe prior to a phase I/II clinical study and validated the efficacy of the system in the treatment of cutaneous murine gastrointestinal tumours. In addition, we established the safety and utility of endoscopically-delivered electroporation through evaluation in a porcine model and by treating canine colorectal tumours. The second leg of our stool involved immunotherapy. We opted for a combination regime of Treg depletion and immunotherapy with the cytokine, pGMCSF-B7.1. While we observed a modest but significant improvement of primary tumour burden, the combination regime had the remarkable effect of eradicating pre-existing, established lung metastases when compared to the use of either treatment alone. The potential clinical implications of this should not be understated as nine out of ten cancer deaths are directly attributable to metastatic disease burden. The third and final leg of our anti-cancer strategy involved the development of a DNA-based enhanced expression vector (pEEV), with improved expression capabilities across a range of tissue histologies over standard non-viral DNA vectors. Following on from this observation, we then utilised this pEEV vector system in combination with the immune cytokine GMCSF-B7.1 leading to robust recruitment of immune effector cells with consequent potent, durable and transferable tumour antigen-specific responses. Advisors/Committee Members: Soden, Declan, Forde, Patrick.

Subjects/Keywords: Electroporation; Electrochemotherapy; EndoVe; Cancer immunogene therapy; Immune therapy; Gene therapy

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APA (6^th Edition):

Sadadcharam, M. (2015). Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. (Thesis). University College Cork. Retrieved from http://hdl.handle.net/10468/3484

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):

Sadadcharam, Mira. “Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.” 2015. Thesis, University College Cork. Accessed January 21, 2021. http://hdl.handle.net/10468/3484.

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

MLA Handbook (7^th Edition):

Sadadcharam, Mira. “Expanding the use of electroporation from cutaneous to intraluminal and systemic applications.” 2015. Web. 21 Jan 2021.

Vancouver:

Sadadcharam M. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. [Internet] [Thesis]. University College Cork; 2015. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/10468/3484.

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

Council of Science Editors:

Sadadcharam M. Expanding the use of electroporation from cutaneous to intraluminal and systemic applications. [Thesis]. University College Cork; 2015. Available from: http://hdl.handle.net/10468/3484

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

University of California – Berkeley

27. Bai, Yong. In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent.

Degree: Comparative Biochemistry, 2010, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/5kx3k87c

► Engineered M1GS ribozyme derived from RNA subunit of E. coli can be a very promising antiviral agent. The focus of this dissertation has been to… (more)

▼ Engineered M1GS ribozyme derived from RNA subunit of E. coli can be a very promising antiviral agent. The focus of this dissertation has been to develop a method for stable, safe and effective delivery of ribozyme into the viral infection sites of an animal and achieve antiviral effect. First, the M1GS expressing constructs which target the overlapping mRNA region of MCMV assembly protein (mAP) and M80 were successfully delivered into MCMV-infected CB17 SCID mice through a modified hydrodynamic transfection procedure and block viral pathogenesis. The expression of ribozymes was observed in the liver and spleen. Compared to the control groups, animals receiving the functional ribozyme construct exhibited a significant reduction of viral gene expression and infection. Viral titers in the spleens, livers, lungs, and salivary glands of the functional ribozyme-treated SCID mice at 21 days after infection were 200 to 2,000 fold lower than those in the control animals. Moreover, survival of the infected animals significantly improved upon receiving the functional ribozyme construct. This study successfully uses a hydrodynamic transfection method to deliver ribozymes into animal and demonstrates the feasibility of using M1GS ribozymes for inhibition of viral gene expression in animals. Second, using human cytomegalovirus (HCMV) infection of differentiated macrophages as the model, the study showed that Salmonella can efficiently deliver RNase P-based ribozyme sequence in human specific human cells, leading to substantial ribozyme expression and effective inhibition of viral infection. A functional M1GS ribozyme was constructed to target the overlapping mRNA region of the capsid scaffolding protein (CSP) and assemblin, which are essential for viral capsid formation. Substantial expression of ribozymes was observed in cells that were treated with attenuated Salmonella strains carrying the ribozyme sequence constructs. A reduction of 87 - 90% in viral CSP expression and a reduction of about 5,000 fold in viral growth were observed in cells that were treated with Salmonella carrying the sequence of the functional ribozyme but not with control groups. This study showed for the first time that ribozymes delivered via Salmonella-based vectors are highly active and specific in blocking viral infection in cultured cells. Third, a functional M1GS ribozyme that targets the overlapping mRNA region of MCMV M80.5 and protease was constructed. A novel attenuated strain of Salmonella, which exhibited efficient gene transfer activity and little virulence in mice, was constructed and used for delivery of anti-MCMV ribozyme in vivo. Oral inoculation of the attenuated Salmonella strain in mice efficiently delivered antiviral M1GS RNA into targeted organs, leading to substantial expression of ribozyme without causing significant adverse effects in the animals. Furthermore, the MCMV infected mice that were treated orally with Salmonella carrying the functional M1GS sequence displayed reduced viral gene expression, decreased viral titers and…

Subjects/Keywords: Biology; Virology; CMV; delivery; gene therapy; Ribozyme

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

APA (6^th Edition):

Bai, Y. (2010). In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/5kx3k87c

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):

Bai, Yong. “In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent.” 2010. Thesis, University of California – Berkeley. Accessed January 21, 2021. http://www.escholarship.org/uc/item/5kx3k87c.

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

MLA Handbook (7^th Edition):

Bai, Yong. “In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent.” 2010. Web. 21 Jan 2021.

Vancouver:

Bai Y. In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent. [Internet] [Thesis]. University of California – Berkeley; 2010. [cited 2021 Jan 21]. Available from: http://www.escholarship.org/uc/item/5kx3k87c.

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

Council of Science Editors:

Bai Y. In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent. [Thesis]. University of California – Berkeley; 2010. Available from: http://www.escholarship.org/uc/item/5kx3k87c

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

University of California – San Diego

28. Corleto, Jose Alfredo. Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat.

Degree: Biomedical Sciences, 2016, University of California – San Diego

URL: http://www.escholarship.org/uc/item/64h01790

► Spinal cord injury is a problem that carries with it many implications including changes in motor circuit action that then lead to development of muscle… (more)

▼ Spinal cord injury is a problem that carries with it many implications including changes in motor circuit action that then lead to development of muscle spasticity, hyperreflexia, and loss of inhibitory response stemming from injury. These changes contribute to muscle spasms elicited by casual stimulation of afferent fibers that then lead to changes in muscle action and to a decrease in the quality of life. Here, we developed a thoracic 9 spinal cord transection injury model in Sprague-Dawley rats to study the changes in motor circuitry in these paraplegic rats. For the first part of my thesis work, we used electrophysiology in this SCI model to study the development of gastrocnemius muscle spasticity, and also the presence of electrical stimulation- and tactile-evoked hyperreflexia at chronic phase following injury. The second part of my thesis focused on the use of clinical pharmacology (Baclofen, GABAb agonist and Tizanidine, α2 adrenergic agonist) and non-used avenues (NGX424, ampa/kainate antagonist) to look at the amelioration of spasticity and spinal hyper-reflexia. The third part of my thesis was aimed at using experimental gene therapy and to test the effect of spinal GAD65 gene upregulation (as achieved by spinal IT or SP AAV9-GAD65 delivery) on chronic spasticity.Our results are sequentially organized as follows: 1) Characterization of time-dependent appearance of muscle spasticity and spinal hyper-reflexia after spinal Th9 transection in rat as defined by i) ankle-rotation evoked increase in muscle resistance, ii) tactile stimulus-evoked EMG response, and iii) electrical stimulus (H-reflex) defined muscle hyper-reflexia. 2) Characterization of anti-spastic potency of clinically validated anti-spastic agents in rat Th 9 spinal transection-induced chronic spasticity model. 3) Effect of spinal GAD65 gene upregulation in combination with systemic tiagabine (GABA uptake inhibitor) treatment on chronic muscle spasticity. In conclusion, my work has demonstrated that our T9 TSCT model can recapitulate several pathologic neurological phenotypes (muscle spasticity, spinal hyper-reflexia) seen in human patients suffering from chronic spinal cord injury. Chronic muscle spasticity measured in the rat model is effectively suppressed by clinically validated anti-spastic agents, which suggests that this model represents an appropriate avenue for development of new anti-spastic therapies.

Subjects/Keywords: Biology; Gene Therapy; Pharmacology; Spinal Cord Injury

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

APA (6^th Edition):

Corleto, J. A. (2016). Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/64h01790

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):

Corleto, Jose Alfredo. “Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat.” 2016. Thesis, University of California – San Diego. Accessed January 21, 2021. http://www.escholarship.org/uc/item/64h01790.

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

MLA Handbook (7^th Edition):

Corleto, Jose Alfredo. “Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat.” 2016. Web. 21 Jan 2021.

Vancouver:

Corleto JA. Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Jan 21]. Available from: http://www.escholarship.org/uc/item/64h01790.

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

Council of Science Editors:

Corleto JA. Electrophysiological and neurological characterization of a thoracic 9 model of spinal cord injury-induced muscle spasticity and the therapeutic anti-spastic effect following spinal GAD65 gene delivery in the rat. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/64h01790

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

University of Rochester

29. Hine, Christopher M.; Gorbunova, Vera. Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter.

Degree: PhD, 2011, University of Rochester

URL: http://hdl.handle.net/1802/15811

► Cancer is one of the top three leading causes of death worldwide. Its physical, social and economic impact on patients, their families and society are… (more)

▼ Cancer is one of the top three leading causes of death worldwide. Its physical, social and economic impact on patients, their families and society are devastating. Basic, translational and clinical research that encompasses cancer prevention, diagnosis and treatment are essential and needed to lower or eradicate the incidence of this disease. To address this issue, I compared: (1) Tumor suppressive mechanisms in long and short-lived mammals and (2) Rad51 promoter-based construct activity in cancerous and noncancerous human cells for the development of targeted cancer gene therapies and diagnostics. (1) The naked mole rat (NMR) (Heterocephalus glaber) is of interest to aging and cancer researchers due to its maximum lifespan exceeding 30 years and having no reported cases of cancer. Previously, our lab identified a novel tumor suppressor mechanism wherein NMR fibroblasts display resistance to malignant transformation due to contact inhibition hypersensitivity, termed early contact inhibition (E.C.I.). The external and upstream signals for NMR cells to undergo E.C.I. are not known. Here, I show signaling of E.C.I. is induced by NMR cells secreting high molecular weight (HMW) (>6,000 kDa) hyaluronic acid (HA), an extracellular glycosaminoglycan, through upregulation of HA synthase 2. HMW-HA, interacting with NMR specific forms of the transmembrane HA receptor CD44, induced the signaling cascade needed to initiate ECI and resistance to malignant transformation by sequestering the NF2 tumor suppressor in a growth inhibitory state. Also, an abundance of HA in NMR tissues suggests a cytoprotective barrier due to HMW-HA protecting cells from oxidative and mechanical stress. I conclude that NMR’s longevity and cancer resistance are due, in part, to their utilization of HMW-HA. (2) Rad51, involved in homologous recombination, is overexpressed in the majority of human cancers, and its expression correlates with a poor prognosis. Using cell culture and xenograft systems, I show the differential expression of Rad51 can be exploited in Rad51 promoter-based cancer therapy and diagnostic systems. Placing a reporter ORF downstream of the Rad51 promoter displayed an average difference in promoter activity between cancer and normal cells of over 800-fold. A construct comprised of the Rad51 promoter driven expression of the diphtheria toxin A gene (pRad51-DTA) destroyed a variety of human cancer cell lines, with minimal to no toxicity in noncancerous human cells. Delivery of Rad51 promoter-based constructs in vivo using jetPEI nanoparticles was used to visualize and treat mice with human cervical cancer xenografts. pRad51-Luc, a construct containing firefly luciferase under the Rad51 promoter, was used for tumor detection and imaging. Mice with cancer, but not without, displayed strong bioluminescence, indicating tumor specific in vivo activity of pRad51-Luc. Treatment with pRad51-DTA decreased tumor mass of subcutaneous (SC) and intraperitoneal (IP) tumors by 6-fold and 4-fold, respectively, along with a 23-fold reduction of…

Subjects/Keywords: Cancer; Gene Therapy; Naked Mole Rat

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

APA (6^th Edition):

Hine, Christopher M.; Gorbunova, V. (2011). Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/15811

Chicago Manual of Style (16^th Edition):

Hine, Christopher M.; Gorbunova, Vera. “Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter.” 2011. Doctoral Dissertation, University of Rochester. Accessed January 21, 2021. http://hdl.handle.net/1802/15811.

MLA Handbook (7^th Edition):

Hine, Christopher M.; Gorbunova, Vera. “Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter.” 2011. Web. 21 Jan 2021.

Vancouver:

Hine, Christopher M.; Gorbunova V. Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter. [Internet] [Doctoral dissertation]. University of Rochester; 2011. [cited 2021 Jan 21]. Available from: http://hdl.handle.net/1802/15811.

Council of Science Editors:

Hine, Christopher M.; Gorbunova V. Defying and Defeating Cancer: Hyaluronic Acid and the Rad51 Promoter. [Doctoral Dissertation]. University of Rochester; 2011. Available from: http://hdl.handle.net/1802/15811

University of Utah

30. Christensen, Lane. Reducible poly(amido ethylenimine)s for gene delivery;.

Degree: PhD, Pharmaceutics & Pharmaceutical Chemistry;, 2007, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085

► Much has been learned from the success and, more so, from the early failures of gene therapy, thereby providing a realistic therapeutic alternative for a… (more)

▼ Much has been learned from the success and, more so, from the early failures of gene therapy, thereby providing a realistic therapeutic alternative for a variety of diseases and genetic disorders in the foreseeable future. Carrier mediated toxicity and low expression has hampered the use of nonviral carriers in vivo. The purpose of this research was to develop a new glass of gene carrier by synthesizing polymers consisting of reducible ethylenimine monomeric units aimed at taking advantage of the cellular redox gradient between the intra-and intercellular environment. These polymers were prepared and characterized for their potential over existing cationic nonviral gene carries. The first section of this dissertation addresses the synthesis and characterization of the class of reducible polymers termed disulfide reducible poly(amido ethylenimine)s (SS-PAEIs). Specifically, three polymers were synthesized varying only in the length of the ethylenimine monomer used in the Michael addition synthesis with cystamine bisacrylamide. The polymers were optimized with respect to their particle size, charge potential, buffering capacity, degree of branching, cellular toxicity and their role in medicating reporter gene expression in a variety of cell lines. Results showed that all three SS-PAEIs facilitate high levels of gene expression up to 20 x higher than the postitive control without significant interaction in the presence of serum proteins or without compromising levels of toxicity. Multiple experiments using these carriers also showed the release of plasmid DNA (pDNA) was dependent upon the oxidative environment. The second half of the dissertation covers the transition from in vitro characterization to therapeutic gene delivery via SS-PAEI polymers in vitro and in vivo. Delivery of hyposia-inducible VEGF plasmid showed up to 76 x higher VIGF expression in primay rat cardiomyoblasts under hypoxic conditions compared to normal conditions. More importantly, a significant amount of VEGF was detected around the region of infarct in ischemic rabbit myocardium four days after injection. In addition, construction and delivery of an eNOS plasmid showed significant levels of delivery in primary human adult cardiac progenitor cells compared to a control carrier leading to the future plans of efficacy experiments in vivo.

Subjects/Keywords: Polymetric Drug Delivery System; Gene Therapy

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

APA (6^th Edition):

Christensen, L. (2007). Reducible poly(amido ethylenimine)s for gene delivery;. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085

Chicago Manual of Style (16^th Edition):

Christensen, Lane. “Reducible poly(amido ethylenimine)s for gene delivery;.” 2007. Doctoral Dissertation, University of Utah. Accessed January 21, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085.

MLA Handbook (7^th Edition):

Christensen, Lane. “Reducible poly(amido ethylenimine)s for gene delivery;.” 2007. Web. 21 Jan 2021.

Vancouver:

Christensen L. Reducible poly(amido ethylenimine)s for gene delivery;. [Internet] [Doctoral dissertation]. University of Utah; 2007. [cited 2021 Jan 21]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085.

Council of Science Editors:

Christensen L. Reducible poly(amido ethylenimine)s for gene delivery;. [Doctoral Dissertation]. University of Utah; 2007. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085

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Open Access Theses and Dissertations