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University of Alberta
1.
Rose, Laura C.
In vivo gene delivery with non-viral carriers.
Degree: PhD, Department of Biomedical Engineering, 2013, University of Alberta
URL: https://era.library.ualberta.ca/files/5t34sj69w
► Gene delivery is an emerging therapy for treatment of many different diseases and conditions, with the first therapy recently approved for clinical use. This thesis…
(more)
▼ Gene delivery is an emerging therapy for treatment of
many different diseases and conditions, with the first therapy
recently approved for clinical use. This thesis investigates
non-viral carriers for gene delivery for bone regeneration, with an
emphasis on the mechanisms of plasmid DNA (pDNA) delivery and
methods to improve transfection. Polyethylenimine (PEI, 2 kDa)
modified with linoleic acid (PEI-LA) was found to give transfection
rates comparable to viral vectors both in vitro and in vivo. The
PEI-LA/pDNA complexes were found to display a decreased
transfection efficiency over time, but a gelatin coating was found
to prevent this loss of transfection. The gelatin-coated particles
also led to increased transfection in vivo, allowing lower doses of
pDNA to be used. Finally, we developed a novel quantitative PCR
(qPCR) method to detect pDNA bound in a polymer complex such that
the pharmacokinetics could be investigated. The pDNA delivered
without a polymeric carrier was degraded very rapidly, while pDNA
from PEI and PEI-LA complexes were detectable for two and four
weeks respectively. For polymeric complexes, the qPCR method was in
good agreement with studies tracking fluorescently labelled pDNA.
Similar to in vitro results, PEI complexes gave no gene expression
while PEI-LA complexes gave gene expression for at least four
weeks. Although no bone regeneration was observed following
delivery of complexes, these studies provide crucial information on
the non-viral gene delivery in vivo.
Subjects/Keywords: Gene delivery
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APA (6th Edition):
Rose, L. C. (2013). In vivo gene delivery with non-viral carriers. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/5t34sj69w
Chicago Manual of Style (16th Edition):
Rose, Laura C. “In vivo gene delivery with non-viral carriers.” 2013. Doctoral Dissertation, University of Alberta. Accessed January 25, 2021.
https://era.library.ualberta.ca/files/5t34sj69w.
MLA Handbook (7th Edition):
Rose, Laura C. “In vivo gene delivery with non-viral carriers.” 2013. Web. 25 Jan 2021.
Vancouver:
Rose LC. In vivo gene delivery with non-viral carriers. [Internet] [Doctoral dissertation]. University of Alberta; 2013. [cited 2021 Jan 25].
Available from: https://era.library.ualberta.ca/files/5t34sj69w.
Council of Science Editors:
Rose LC. In vivo gene delivery with non-viral carriers. [Doctoral Dissertation]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/5t34sj69w

University of Waterloo
2.
Rafiee, Amirreza.
Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape.
Degree: 2018, University of Waterloo
URL: http://hdl.handle.net/10012/13734
► The development of non-viral gene delivery vectors is highly challenging and aims to provide a safe while cost-effective manufacturing alternative to viral vectors. Eleven novel…
(more)
▼ The development of non-viral gene delivery vectors is highly challenging and aims to provide a safe while cost-effective manufacturing alternative to viral vectors. Eleven novel gemini surfactants (G4-G14) were designed and synthesized by covalent linking of 10 different functional moieties (R = R1-R10) to the spacer regions of gemini surfactants (chemical formula m-s-m; m = saturated 12, 18 carbon alkyl chains, s = R-linked-imino-substituted-7 methylene spacer group (7NR)). These R-functionalities include imidazole and thiol containing functional groups (R1 = imidazolepropionyl, R2 = thiopropionyl; for synthesis of G4 (18-7NR1-18) and G5 (18-7NR2-18)), linear RGD derivatives (R3 = RGDG, R4 = GRGDSPG; for synthesis of G6 (12-7NR3-12), G7 (18-7NR3-18), G8 (18-7NR4-18)), polyhistidine derivatives (R5 = E(H)5; for synthesis of G9 (18-7NR5-18)), bifunctional RGD-polyhistidine peptides (R6 = EGRGDSPG(H)5; for synthesis of G10 (18-7NR6-18)), and arginine-rich peptide motifs (R7 = Suc-(E)2G(R)2, R8 = Suc-(E)2G(R)3, R9 = Suc-(E)2(G)3(R)3, R10 = Suc-DE(G)3(R)3); for synthesis of G11 (18-7NR7-18), G12 (18-7NR8-18), G13 (18-7NR9-18), G14 (18-7NR10-18)]. The RGD-functionalized gemini surfactants were evaluated for targeted gene delivery. Further, the impact of non-covalent addition of designed peptide enhancers (7 types; PA-PG) [zwitterionic RGD peptide enhancer (PA), cationic peptide enhancers rich in histidine and/or arginine (PB, PD, PF), or bifunctional cationic, RGD peptide enhancers (PC = PA+ PB, PE = PA+ PD, PG = PA+ PF)] were examined for development of peptide-based lipopolyplexes, named peptide-driven tri-modal gene delivery systems (PDTMG). The PDTMG were formulated using peptide enhancers/gemini surfactants/1,2-dioleyl-sn-glycero-3-phosphoethanolamine (DOPE) helper lipid, for in vitro delivery of green fluorescent protein (GFP)-expressing plasmid DNA. Using quantitative flow cytometry, transfection activity was investigated by both the percentage of the transfected cells and the intensity of GFP expression level determined by mean fluorescence intensities (MFI). The correlation of the transfection activity and viability to the physicochemical properties of delivery systems, size and zeta potential, were identified to advance formulation strategies for development of a potent delivery system with negligible cytotoxicity. These include optimization of cationic quaternary ammonium of gemini surfactants/anionic phosphate of DNA (N/P) mole ratios (ρ values), DOPE/gemini molar ratios (r values), and the molarity of the compositional elements in the formulation mixtures (MP, MG and ML for molar concentrations of peptide enhancers (P), gemini surfactants (G) and DOPE helper lipids (L), respectively). In vitro transfection studies demonstrated that among PDTMG delivery systems formulated using fourteen different gemini surfactants [G1-G14] differing in their headgroups and alkyl tails lengths (i.e., s = 3, 7NH, 7NR1-10; m = 12, 18), remarkably gemini surfactants with short RGD functional headgroups and C18 alkyl tails (G7 and…
Subjects/Keywords: Gene Delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Rafiee, A. (2018). Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/13734
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rafiee, Amirreza. “Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape.” 2018. Thesis, University of Waterloo. Accessed January 25, 2021.
http://hdl.handle.net/10012/13734.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rafiee, Amirreza. “Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape.” 2018. Web. 25 Jan 2021.
Vancouver:
Rafiee A. Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10012/13734.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rafiee A. Peptide-Driven Tri-Modal Gene Delivery Systems (PDTMG): Novel Versatile Peptide-Based Lipopolyplexes Incorporating Peptide-Functionalized Gemini Surfactants for Targeted Gene Therapy- Implementation of RGD Motifs as a Means for Endosomal Escape. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/13734
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Oklahoma
3.
Wang, Dongdong.
TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES.
Degree: PhD, 2016, University of Oklahoma
URL: http://hdl.handle.net/11244/34732
► Stem cells hold great potential for the regenerative medicine and tissue engineering. Controlling the fate of stem cell in a reliable method still remains a…
(more)
▼ Stem cells hold great potential for the regenerative medicine and tissue engineering. Controlling the fate of stem cell in a reliable method still remains a problem. The strategies for directing the fate of stem cells include biophysical cues (e.g. matrix stiffness, topography, and extracellular forces), biochemical cues (e.g. growth factors, cytokines and chemokines) and cellular reprogramming (e.g.
gene delivery). Controlled
delivery of specific genes, such as transcription factor encoding genes, to stem cells is a promising strategy for stem-cell based therapy.
Gene delivery methods include two major categories: viral vectors and non-viral vectors. Non-viral
gene delivery vectors hold great promise for
gene therapy due to the safety concerns with viral vectors. However, the application of non-viral vectors is hindered by their low transfection efficiency. Herein, in order to tackle this challenge, we endeavored to develop non-viral vectors with efficient
gene delivery and low toxicity to hard-to-transfect MSCs.
First, we focused on the identification and characterization of novel MSCs-targeting peptides using phage libraries. A peptide (VTAMEPGQ) that can home to rat mesenchymal stem cells (rMSCs) was identified. This VTAMEPGQ peptide demonstrated high affinity and specificity to rMSCs. When integrated into liposome protamine/DNA lipoplex (LPD) system, the peptide significantly enhanced
gene transfection efficiency to rMSCs.
Second, we focused on developing efficiently and chemically-defined LPD-based
gene delivery system to rMSCs. We employed three-folds reiterated VTAMEPGQ peptides, nuclear localization signal and liposome/protamine complex to
delivery vascular endothelial growth factor (VEGF) reporter
gene to rMSCs. The developed LPD
gene delivery complex demonstrated high transfection efficiency and long-lasting
gene expression profile.
Third, we developed Glutathione (GSH) cleavable magnetic/silica nanoclusters integrating MSC-homing major coat protein (pVIII) for targeted
gene delivery. pVIII proteins were purified from the VTAMEPGQ-sequence bearing phage identified by phage display technique. The intracellular GSH is responsible for cleaving the S-S bond to dissociate the nanoclusters to release DNA. The as-synthesized
gene delivery complex also showed satisfactory
gene transfection result to rMSCs.
Finally, we studied the role of cell-binding peptides in directing the stem cell differentiation. We take advantage of the three peptides, which are selected by phage display and show different binding affinities against MSCs, to investigate the osteogenic differentiation of MSCs. Surprisingly, we discovered that the peptide (VTAMEPGQ) with the highest MSC-binding affinity induced the osteogenic differentiation of MSCs most efficiently. We propose that the MSC-binding peptides may bind to the bone morphometric protein (BMP) receptors to initiate the osteogenic differentiation pathway.
Advisors/Committee Members: Mao, Chuanbin (advisor), Russell, Scott (committee member), Rice, Charles (committee member), West, Ann (committee member), Yip, Wai Tak (committee member).
Subjects/Keywords: Gene delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, D. (2016). TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/34732
Chicago Manual of Style (16th Edition):
Wang, Dongdong. “TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES.” 2016. Doctoral Dissertation, University of Oklahoma. Accessed January 25, 2021.
http://hdl.handle.net/11244/34732.
MLA Handbook (7th Edition):
Wang, Dongdong. “TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES.” 2016. Web. 25 Jan 2021.
Vancouver:
Wang D. TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES. [Internet] [Doctoral dissertation]. University of Oklahoma; 2016. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/11244/34732.
Council of Science Editors:
Wang D. TARGETED GENE DELIVERY TO MESENCHYMAL STEM CELLS USING NANOPARTICLES. [Doctoral Dissertation]. University of Oklahoma; 2016. Available from: http://hdl.handle.net/11244/34732
4.
Sunshine, Joel Chaim.
Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37881
► This thesis discusses the development of biodegradable polymers, nanoparticles, and microparticles for gene delivery and immune activation. The bulk of this thesis focuses on trying…
(more)
▼ This thesis discusses the development of biodegradable polymers, nanoparticles, and microparticles for
gene delivery and immune activation. The bulk of this thesis focuses on trying to understand basic principles important to the development of polymer-based
gene delivery nanoparticles and acellular artificial antigen presenting cells (aAPC) for CD8+ T cell activation, In addition to the basic work, these technologies can be applied to many areas of human health and I have focused on applications in cancer and ophthalmology. The root cause of many diseases has a genetic component, from single
gene disorders like hemophilia to multifactorial disorders like cancer. As a result,
gene therapy has enormous therapeutic potential if it can be done safely and efficiently. The vast majority of the effort into
gene therapy has been directed at co-opting viruses as vectors for
gene delivery, as viruses have evolved to be supremely efficient at getting their genetic information
into foreign cells, but viral
gene therapy has been hampered by high profile setbacks in clinical trials, owing to the potential for insertional mutagenesis and overly aggressive host immune responses to the vector. Theoretically, non-viral
gene therapy should overcome these limitations by reducing the host response, enabling unlimited cargo capacity, and should be easier to produce and standardize. However, non-viral
gene therapy has thus far been unable to achieve the required high transfection efficacies seen with viruses. A class of synthetic cationic polymers, poly(ß-amino)esters (PBAEs), have shown promise, but in order to develop next-generation synthetic polymer vectors for
gene delivery, a deeper understanding of the relationship between polymer design and functional outcomes is required. In this thesis, I investigated structure-function relationships within a library of PBAEs that we developed, with an eye towards investigating the impact of polymer properties on critical
barriers to intracellular
delivery. To extend this work, we looked to develop PBAEs for non-viral
gene delivery to the eye, by investigating how different particle formulations might enable differential
delivery to ocular cell types, and by performing a pilot study looking at in vivo
gene delivery to the mouse retina via subretinal injection. We found that polymer hydrophobicity was a critical dimension that significantly effected polymer vector performance. We also found that the amine termini of PBAEs were critical to vector function at the level of nanoparticle uptake even though they did not substantially alter any putative key nanoparticle properties. We found that polymer formulations that worked well for one cell class worked well for another cell type within that class but may not work well for a different cell class, and demonstrated that PBAEs could engender high levels of
gene expression in the mouse retina. Tumor immunotherapy requires the activation of cytotoxic T
lymphocytes (CTLs) against tumor-specific targets. This activation process occurs in vivo through the…
Advisors/Committee Members: Schneck, Jonathan P (advisor).
Subjects/Keywords: Gene Delivery; Immunoengineering
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sunshine, J. C. (2014). Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37881
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sunshine, Joel Chaim. “Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation.” 2014. Thesis, Johns Hopkins University. Accessed January 25, 2021.
http://jhir.library.jhu.edu/handle/1774.2/37881.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sunshine, Joel Chaim. “Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation.” 2014. Web. 25 Jan 2021.
Vancouver:
Sunshine JC. Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Jan 25].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37881.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sunshine JC. Biodegradable Nano- and Microparticles for Gene Delivery and Immune Activation. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37881
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
5.
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)
▼ 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 to the liver of small animals, and its clinical applicability in large animals has been demonstrated. Previous studies focused on functional analyses of therapeutic genes in animals with normal livers and little, however, is known regarding its effectiveness and safety in animals with liver fibrosis. Therefore, this study aimed to examine the effects of liver fibrosis on hydrodynamic gene delivery efficiency using a rat liver fibrosis model. We demonstrated for the first time, using pCMV-Luc plasmid, that this procedure is safe and that the amount of fibrotic tissue in the liver decreases gene delivery efficiency, resulting in decrease in luciferase activity depending on the volume of fibrotic tissue in the liver and the number of hepatocytes that are immunohistochemically stained positive for transgene product. We further demonstrate that antifibrotic gene therapy with matrix metalloproteinase-13 gene reduces liver fibrosis and improves efficiency of hydrodynamic gene delivery. These results demonstrate the negative effects of fibrotic tissue on hydrodynamic gene delivery and its recovery by appropriate antifibrotic therapy
Subjects/Keywords: gene therapy; hydrodynamic gene delivery; liver fibrosis; MMP13; nonviral gene delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th 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 (16th 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 25, 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 (7th 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. 25 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 25].
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

University of Adelaide
6.
Xiong, Lin.
Mesoporous Silica Nanocomposites for Drug and Gene Delivery.
Degree: 2016, University of Adelaide
URL: http://hdl.handle.net/2440/119077
► A drug delivery system is an essential tool for improving drug therapies by overcoming the limitations of ‘free’ drug delivery including low solubility in water,…
(more)
▼ A drug
delivery system is an essential tool for improving drug therapies by overcoming the limitations of ‘free’ drug
delivery including low solubility in water, poor stability in biological systems, short residence time, unspecific toxicity and side effects. Nowadays, nanomaterials have become ideal vehicles for drug
delivery owing to their very small size and high surface-to-volume ratio. Their small size ensures access to different biological tissues, efficient cellular uptake and facilitates intracellular
delivery of therapeutics. Their high surface area allows for high drug loading and the attachment of various functional groups. Among various nanomaterials, mesoporous silica nanoparticles show great potential for
delivery application due to their good biocompatibility, well-developed mesoporosity, and versatile surface functionalization. However, to construct an efficient
delivery system, the primary silica nanoparticles still need to be optimized in structure to load large biomolecules and modified in surface chemistry to achieve efficient targeting and release control. With this aim, this Ph.D thesis has demonstrated the design and fabrication of a serial of novel mesoporous silica based nanocomposites as drug and
gene delivery carriers. These researches include: (1) We firstly studied the controllable synthesis of stellate mesoporous silica nanoparticles with radial pore morphology. By using triethanolamine as the base catalyst and adjusting the surfactant composition, reaction temperature and time, and reagent ratio, we demonstrated that the particle size of these nanomaterials could be tailored continuously from 50 to 140 nm and the pore size could be tuned from 2 to 20 nm, respectively. After further functionalization with low molecular weight poly(ethyleneimine), these nanocomposites demonstrated good capability for intracellular
delivery of the anticancer drug doxorubicin. (2) Then, we developed a cancer cell-specific nuclear-targeted
delivery system based on mesoporous silica nanoparticles. Mesoporous silica nanoparticles with 40 nm particle size were modified with dual targeting ligands, i.e., folic acid for cancer cell targeting and dexamethasone for nuclear targeting. The resulting nanocarriers could not only enhance the inhibition efficacy of doxorubicin on cancerous Hela cells through active nucleus accumulation but also reduce toxic side effects on normal cells though receptor-mediated selective cellular uptake. (3) Next, we studied magnetic core–shell silica nanoparticles with large radial mesopores for small interfering RNA (siRNA)
delivery. These nanoparticles possess both high loading capacity of siRNA and strong magnetic response under an external magnetic field. Furthermore, an acid-liable coating composed of tannic acid was applied to further protect the siRNA loaded in the large pores. The coating also increased the dispersion stability of the siRNA-loaded carrier and served as a pH-responsive releasing switch. Using these nanocarriers, enhanced
delivery of functional siRNA into human…
Advisors/Committee Members: Qiao, Shizhang (advisor), School of Chemical Engineering (school).
Subjects/Keywords: Mesoporous silica; nanomaterials; drug delivery; gene delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Xiong, L. (2016). Mesoporous Silica Nanocomposites for Drug and Gene Delivery. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/119077
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Xiong, Lin. “Mesoporous Silica Nanocomposites for Drug and Gene Delivery.” 2016. Thesis, University of Adelaide. Accessed January 25, 2021.
http://hdl.handle.net/2440/119077.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Xiong, Lin. “Mesoporous Silica Nanocomposites for Drug and Gene Delivery.” 2016. Web. 25 Jan 2021.
Vancouver:
Xiong L. Mesoporous Silica Nanocomposites for Drug and Gene Delivery. [Internet] [Thesis]. University of Adelaide; 2016. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/2440/119077.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Xiong L. Mesoporous Silica Nanocomposites for Drug and Gene Delivery. [Thesis]. University of Adelaide; 2016. Available from: http://hdl.handle.net/2440/119077
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Alberta
7.
Fitzsimmons, Ross.
Novel polymer and lipid-based nanocarriers for gene
delivery.
Degree: MS, Department of Biomedical Engineering, 2011, University of Alberta
URL: https://era.library.ualberta.ca/files/gf06g346v
► The following thesis describes original studies assessing the gene delivery efficacy of novel non-viral carrier combinations. The first panel of non-viral carriers tested are termed…
(more)
▼ The following thesis describes original studies
assessing the gene delivery efficacy of novel non-viral carrier
combinations. The first panel of non-viral carriers tested are
termed AVPs (artificial viral particles), in reference to their
structural similarity to enveloped viruses, and were fabricated in
a composite manner using a variety of polymers and lipids in order
to deliver plasmid DNA. The most effective carrier found in these
studies was 25 kDa PEI (polyethylenimine), with none of the AVPs
showing a clear superior effect to that of 25 kDa PEI. While a
highly effective gene carrier, PEI is extremely cytotoxic and hence
PEI was conjugated with PEG (polyethylene glycol) in attempt to
decrease its toxicity while maintaining its functionality.
Ultimately, it was found that PEGylation generally decreased the
transfection efficacy of PEI, but under ideal conditions of PEG
substitution and polymer/DNA (w/w) ratio, this decrease in efficacy
can be circumvented.
Subjects/Keywords: gene delivery; polymers; liposomes
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Chicago ·
MLA ·
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APA (6th Edition):
Fitzsimmons, R. (2011). Novel polymer and lipid-based nanocarriers for gene
delivery. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/gf06g346v
Chicago Manual of Style (16th Edition):
Fitzsimmons, Ross. “Novel polymer and lipid-based nanocarriers for gene
delivery.” 2011. Masters Thesis, University of Alberta. Accessed January 25, 2021.
https://era.library.ualberta.ca/files/gf06g346v.
MLA Handbook (7th Edition):
Fitzsimmons, Ross. “Novel polymer and lipid-based nanocarriers for gene
delivery.” 2011. Web. 25 Jan 2021.
Vancouver:
Fitzsimmons R. Novel polymer and lipid-based nanocarriers for gene
delivery. [Internet] [Masters thesis]. University of Alberta; 2011. [cited 2021 Jan 25].
Available from: https://era.library.ualberta.ca/files/gf06g346v.
Council of Science Editors:
Fitzsimmons R. Novel polymer and lipid-based nanocarriers for gene
delivery. [Masters Thesis]. University of Alberta; 2011. Available from: https://era.library.ualberta.ca/files/gf06g346v

University of Alberta
8.
Jawanda,Manraj S.
Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications.
Degree: MS, Department of Chemical and Materials
Engineering, 2012, University of Alberta
URL: https://era.library.ualberta.ca/files/g445cf747
► Gene therapy has the potential to treat a variety of hereditary diseases such as diabetes, peanut anaphylaxis, cystic fibrosis and different types of cancer. Gene…
(more)
▼ Gene therapy has the potential to treat a variety of
hereditary diseases such as diabetes, peanut anaphylaxis, cystic
fibrosis and different types of cancer. Gene therapy relies on the
design of a delivery system which can carry a gene of interest into
a cell. The delivery systems can be broken down into two different
types: viral and non-viral carriers. Viruses were the standard for
gene delivery and showed high cell transfection, but on the other
hand would sometimes induce an immunological response. As a result,
there has been a growing interest towards non-viral carriers such
as polymers which are less toxic and biocompatible.
Polyethyleneimine (PEI) is the current standard for non-viral gene
carriers, but has drawbacks such as high toxicity. The effect of
molecular weight and composition on transfection efficiency has
been evaluated for many polymers, but very few studies have been
done on polymer architecture. This study focused on the synthesis
of a hyperbranched phosphorylcholine cationic copolymer that
incorporates a nontoxic and biocompatible polymer known as
poly(2-Methacryoyloxyethyl Phosphorylcholine (MPC)). The
hyperbranched copolymers were synthesized via RAFT polymerization
through the incorporation of a cross linking agent and showed broad
molecular weight distributions. Complete binding to DNA was
achieved with the cationic polymers, however the gene expression
was found to be significantly lower than PEI when transfected into
Hep G2 cells. In the second part of this thesis, elastomer films
were embedded with conductive materials for potential
cardiovascular applications. Polydimethylsiloxane (PDMS) is an
elastomer used in a variety of medical applications because of its
biocompatibility. In this study, Poly(p-phenylene vinylene) (PPV)
and Multi-Walled Carbon Nanotubes (MWNT) which were two different
conductive materials, were embedded into PDMS and composite films
of PPV/PDMS and MWNT/PDMS were synthesized.
Subjects/Keywords: gene delivery; MPC; RAFT
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
S, J. (2012). Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/g445cf747
Chicago Manual of Style (16th Edition):
S, Jawanda,Manraj. “Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications.” 2012. Masters Thesis, University of Alberta. Accessed January 25, 2021.
https://era.library.ualberta.ca/files/g445cf747.
MLA Handbook (7th Edition):
S, Jawanda,Manraj. “Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications.” 2012. Web. 25 Jan 2021.
Vancouver:
S J. Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications. [Internet] [Masters thesis]. University of Alberta; 2012. [cited 2021 Jan 25].
Available from: https://era.library.ualberta.ca/files/g445cf747.
Council of Science Editors:
S J. Hyperbranched Phosphorylcholine Polymers Synthesized via
RAFT Polymerization for Gene Delivery and Synthesis of an
Elastomeric Conductive Polymer for Cardiovascular
Applications. [Masters Thesis]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/g445cf747

University College Cork
9.
Rajendran, Simon.
Ex vivo culture of patient tissue and examination of gene delivery.
Degree: 2014, University College Cork
URL: http://hdl.handle.net/10468/1904
► Gene therapy has emerged as a realistic prospect for the treatment of cancer due to its potential for selective tumour cell targeting. The greatest challenge…
(more)
▼ Gene therapy has emerged as a realistic prospect for the treatment of cancer due to its potential for selective tumour cell targeting. The greatest challenge
gene delivery vectors face is the ability to safely and efficiently deliver genes into target cells. The overall objectives of this thesis are to evaluate the efficacy of various
gene delivery methods in a clinically relevant tumour model and to also investigate potential strategies for tumour selective
delivery. We began with the development of a tumour slice model system using patient waste tissue. This model involves the use of fresh human tumour tissue, cut into thin slices and maintained ex vivo and is universally applicable to
gene delivery methods, using a real-time luminescence detection method to assess
gene delivery. The nature of the ex vivo culture system permitted examination of specific physiological variables, the influence of intratumoural factors and tissue specific effects on vector expression. Adenoviral vectors under the control of the human CXCR4 promoter demonstrated a 'tumour on' and 'normal off' expression profile when compared with the ubiquitously active CMV promoter when tested in patient tumour tissue. In addition, we developed an ex vivo system of changing oxygenation using the hypoxia inducer, cobalt, to mimic the transient hypoxic conditions found in solid tumours. We found that Adenoviral transgene expression was robust in the cycling hypoxic conditions relevant to solid tumours and re-oxygenation of chronically hypoxic tissue enhanced transgene expression. Finally, we demonstrated an AAV-based tumour targeting strategy using a tumour-selective promoter allowing for the efficient targeting of AAV vectors to cancer cells and the sparing of normal tissue in both murine metastatic liver tumours models and patient tissue. The thesis highlights the importance of indepth preclinical assessment of novel therapeutics and may serve as a platform for further testing of novel
gene delivery approaches.
Advisors/Committee Members: Tangney, Mark.
Subjects/Keywords: Gene delivery; Cancer; Adenovirus
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rajendran, S. (2014). Ex vivo culture of patient tissue and examination of gene delivery. (Thesis). University College Cork. Retrieved from http://hdl.handle.net/10468/1904
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rajendran, Simon. “Ex vivo culture of patient tissue and examination of gene delivery.” 2014. Thesis, University College Cork. Accessed January 25, 2021.
http://hdl.handle.net/10468/1904.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rajendran, Simon. “Ex vivo culture of patient tissue and examination of gene delivery.” 2014. Web. 25 Jan 2021.
Vancouver:
Rajendran S. Ex vivo culture of patient tissue and examination of gene delivery. [Internet] [Thesis]. University College Cork; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10468/1904.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rajendran S. Ex vivo culture of patient tissue and examination of gene delivery. [Thesis]. University College Cork; 2014. Available from: http://hdl.handle.net/10468/1904
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rice University
10.
Lee, Esther Joy.
Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.
Degree: PhD, Bioengineering, 2018, Rice University
URL: http://hdl.handle.net/1911/105809
► Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal…
(more)
▼ Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal precision that cannot, however, be achieved through sole reliance on microenvironment-based strategies.
Gene delivery therefore offers a valuable avenue, whereby direct modifications can be made to dynamic systems such as cell populations. The work presented in this thesis explores several strategies for improving control with the intricacies of tissue engineering applications in mind and additionally leverages elements from synthetic biology and synthetic virology. Optogenetic tools based on light-sensitive proteins offer an exquisite option for fine-tuning expression levels with minimal interference and at low cost. Adeno-associated virus (AAV) is employed as the candidate
gene delivery vehicle due to its ability to infect many cell types and good safety profile in humans, which bode well for clinical applications.
The body of work is grouped into three parts. First, the design and construction of a consolidated red/far red light activatable
gene regulatory circuit was pursued with the intent to tune levels of bone morphogenetic protein-2 (BMP-2) expression. The assembly of a large construct had its share of obstacles that eventually led to a downsized strategy, and a number of lessons were accrued from the duration of this endeavor. Second, an all-in-one AAV platform based activatable by blue light was developed and characterized in a series of light induction experiments. Finally, reverse transduction of three AAV serotypes ranging in degree of infectivity in HeLa cells was explored to determine if this strategy could lead to improved transduction efficiency. Parallel comparisons of standard and reverse infection approaches revealed that transduction efficiency could be improved for less amenable serotypes with the latter protocol. We then investigated whether increased transduction efficiency could be explained by higher cellular uptake of AAV. However, internalization assay results could not provide a full explanation for this phenomenon.
Advisors/Committee Members: Mikos, Antonios G (advisor).
Subjects/Keywords: AAV; gene delivery; tissue engineering
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, E. J. (2018). Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105809
Chicago Manual of Style (16th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Doctoral Dissertation, Rice University. Accessed January 25, 2021.
http://hdl.handle.net/1911/105809.
MLA Handbook (7th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Web. 25 Jan 2021.
Vancouver:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/1911/105809.
Council of Science Editors:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105809

Rice University
11.
Lee, Esther Joy.
Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.
Degree: PhD, Bioengineering, 2018, Rice University
URL: http://hdl.handle.net/1911/105810
► Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal…
(more)
▼ Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal precision that cannot, however, be achieved through sole reliance on microenvironment-based strategies.
Gene delivery therefore offers a valuable avenue, whereby direct modifications can be made to dynamic systems such as cell populations. The work presented in this thesis explores several strategies for improving control with the intricacies of tissue engineering applications in mind and additionally leverages elements from synthetic biology and synthetic virology. Optogenetic tools based on light-sensitive proteins offer an exquisite option for fine-tuning expression levels with minimal interference and at low cost. Adeno-associated virus (AAV) is employed as the candidate
gene delivery vehicle due to its ability to infect many cell types and good safety profile in humans, which bode well for clinical applications.
The body of work is grouped into three parts. First, the design and construction of a consolidated red/far red light activatable
gene regulatory circuit was pursued with the intent to tune levels of bone morphogenetic protein-2 (BMP-2) expression. The assembly of a large construct had its share of obstacles that eventually led to a downsized strategy, and a number of lessons were accrued from the duration of this endeavor. Second, an all-in-one AAV platform based activatable by blue light was developed and characterized in a series of light induction experiments. Finally, reverse transduction of three AAV serotypes ranging in degree of infectivity in HeLa cells was explored to determine if this strategy could lead to improved transduction efficiency. Parallel comparisons of standard and reverse infection approaches revealed that transduction efficiency could be improved for less amenable serotypes with the latter protocol. We then investigated whether increased transduction efficiency could be explained by higher cellular uptake of AAV. However, internalization assay results could not provide a full explanation for this phenomenon.
Advisors/Committee Members: Mikos, Antonios G (advisor).
Subjects/Keywords: AAV; gene delivery; tissue engineering
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, E. J. (2018). Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105810
Chicago Manual of Style (16th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Doctoral Dissertation, Rice University. Accessed January 25, 2021.
http://hdl.handle.net/1911/105810.
MLA Handbook (7th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Web. 25 Jan 2021.
Vancouver:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/1911/105810.
Council of Science Editors:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105810

Rice University
12.
Lee, Esther Joy.
Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.
Degree: PhD, Engineering, 2018, Rice University
URL: http://hdl.handle.net/1911/105807
► Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal…
(more)
▼ Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal precision that cannot, however, be achieved through sole reliance on microenvironment-based strategies.
Gene delivery therefore offers a valuable avenue, whereby direct modifications can be made to dynamic systems such as cell populations. The work presented in this thesis explores several strategies for improving control with the intricacies of tissue engineering applications in mind and additionally leverages elements from synthetic biology and synthetic virology. Optogenetic tools based on light-sensitive proteins offer an exquisite option for fine-tuning expression levels with minimal interference and at low cost. Adeno-associated virus (AAV) is employed as the candidate
gene delivery vehicle due to its ability to infect many cell types and good safety profile in humans, which bode well for clinical applications.
The body of work is grouped into three parts. First, the design and construction of a consolidated red/far red light activatable
gene regulatory circuit was pursued with the intent to tune levels of bone morphogenetic protein-2 (BMP-2) expression. The assembly of a large construct had its share of obstacles that eventually led to a downsized strategy, and a number of lessons were accrued from the duration of this endeavor. Second, an all-in-one AAV platform based activatable by blue light was developed and characterized in a series of light induction experiments. Finally, reverse transduction of three AAV serotypes ranging in degree of infectivity in HeLa cells was explored to determine if this strategy could lead to improved transduction efficiency. Parallel comparisons of standard and reverse infection approaches revealed that transduction efficiency could be improved for less amenable serotypes with the latter protocol. We then investigated whether increased transduction efficiency could be explained by higher cellular uptake of AAV. However, internalization assay results could not provide a full explanation for this phenomenon.
Advisors/Committee Members: Mikos, Antonios G (advisor).
Subjects/Keywords: AAV; gene delivery; tissue engineering
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, E. J. (2018). Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105807
Chicago Manual of Style (16th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Doctoral Dissertation, Rice University. Accessed January 25, 2021.
http://hdl.handle.net/1911/105807.
MLA Handbook (7th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Web. 25 Jan 2021.
Vancouver:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/1911/105807.
Council of Science Editors:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105807

Rice University
13.
Lee, Esther Joy.
Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.
Degree: PhD, Bioengineering, 2018, Rice University
URL: http://hdl.handle.net/1911/105808
► Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal…
(more)
▼ Tissue engineering constitutes non-trivial processes that can be promoted through combinations of cells, materials and bioactive factors. The formation of tissues and organs demands spatiotemporal precision that cannot, however, be achieved through sole reliance on microenvironment-based strategies.
Gene delivery therefore offers a valuable avenue, whereby direct modifications can be made to dynamic systems such as cell populations. The work presented in this thesis explores several strategies for improving control with the intricacies of tissue engineering applications in mind and additionally leverages elements from synthetic biology and synthetic virology. Optogenetic tools based on light-sensitive proteins offer an exquisite option for fine-tuning expression levels with minimal interference and at low cost. Adeno-associated virus (AAV) is employed as the candidate
gene delivery vehicle due to its ability to infect many cell types and good safety profile in humans, which bode well for clinical applications.
The body of work is grouped into three parts. First, the design and construction of a consolidated red/far red light activatable
gene regulatory circuit was pursued with the intent to tune levels of bone morphogenetic protein-2 (BMP-2) expression. The assembly of a large construct had its share of obstacles that eventually led to a downsized strategy, and a number of lessons were accrued from the duration of this endeavor. Second, an all-in-one AAV platform based activatable by blue light was developed and characterized in a series of light induction experiments. Finally, reverse transduction of three AAV serotypes ranging in degree of infectivity in HeLa cells was explored to determine if this strategy could lead to improved transduction efficiency. Parallel comparisons of standard and reverse infection approaches revealed that transduction efficiency could be improved for less amenable serotypes with the latter protocol. We then investigated whether increased transduction efficiency could be explained by higher cellular uptake of AAV. However, internalization assay results could not provide a full explanation for this phenomenon.
Advisors/Committee Members: Mikos, Antonios G (advisor).
Subjects/Keywords: AAV; gene delivery; tissue engineering
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, E. J. (2018). Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/105808
Chicago Manual of Style (16th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Doctoral Dissertation, Rice University. Accessed January 25, 2021.
http://hdl.handle.net/1911/105808.
MLA Handbook (7th Edition):
Lee, Esther Joy. “Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering.” 2018. Web. 25 Jan 2021.
Vancouver:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Internet] [Doctoral dissertation]. Rice University; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/1911/105808.
Council of Science Editors:
Lee EJ. Adeno-Associated Virus-Based Gene Delivery Approaches for Tissue Engineering. [Doctoral Dissertation]. Rice University; 2018. Available from: http://hdl.handle.net/1911/105808

University of Minnesota
14.
Tan, Zhe.
Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles.
Degree: PhD, Chemistry, 2019, University of Minnesota
URL: http://hdl.handle.net/11299/211804
► Millions of people are currently suffering from genetic diseases and disorders worldwide and the traditional protein-based treatments are both expensive and require repetitive injections to…
(more)
▼ Millions of people are currently suffering from genetic diseases and disorders worldwide and the traditional protein-based treatments are both expensive and require repetitive injections to maintain long-term effects. Gene therapy, as an alternative, holds great potential by direct delivery of genetic materials such as nucleic acids and genome editing machineries into human body to achieve long-term therapeutic protein expression, malfunctioning gene silencing, and native gene alternation. As a crucial step towards gene therapy, the delivery of genetic materials remains a major challenge, and affordable, efficient, and well-defined delivery vehicles are urgently needed. Synthetic polymers have been explored as plasmid DNA delivery vehicles for decades owing to their low production cost, chemical flexibility, low immunotoxicity, and the ability to encapsulate biomacromolecules. However, the precise control of polymeric vehicle properties by structure-tuning is a general challenge. Hence, the fundamental understanding of polymeric vehicle’s structure-property relationships is of great importance. In addition, polymers as well-documented nucleic acid delivery vehicles, are largely underexplored for their ability to encapsulate, stabilize and deliver RNA-protein conjugates, such as CRISPR/Cas9 ribonucleoprotein, a recently emerged versatile genome editing tool, presumably due to the inherent structural differences between long, semiflexible DNA and globular RNA-protein payload. Herein, several classes of polymeric delivery vehicles were synthesized and investigated, namely, cationic linear polymers, block copolymers, and polymeric micelles. Initially, a systematic comparison of linear polymers and micelles were performed, and vehicle architecture were shown to largely affect DNA complexation ability, complex physical properties, and biological performance. Later on, polymeric micelles were explored as well-defined CRISPR/Cas9 ribonucleoprotein delivery vehicles, and the solvent condition was found to be a key factor that affect particle complexation and gene-editing efficiency. Finally, polymers with liver-targeting ability and cellular membrane-penetration property have been developed and studied for their gene delivery efficiency and cytotoxicity.
Subjects/Keywords: CRISPR; Gene delivery; Nanoparticles; Polymer
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tan, Z. (2019). Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/211804
Chicago Manual of Style (16th Edition):
Tan, Zhe. “Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles.” 2019. Doctoral Dissertation, University of Minnesota. Accessed January 25, 2021.
http://hdl.handle.net/11299/211804.
MLA Handbook (7th Edition):
Tan, Zhe. “Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles.” 2019. Web. 25 Jan 2021.
Vancouver:
Tan Z. Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles. [Internet] [Doctoral dissertation]. University of Minnesota; 2019. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/11299/211804.
Council of Science Editors:
Tan Z. Cationic Polymers and Polymeric Micelles as Plasmid DNA and CRISPR-Cas9 Ribonucleoprotein Delivery Vehicles. [Doctoral Dissertation]. University of Minnesota; 2019. Available from: http://hdl.handle.net/11299/211804

ETH Zürich
15.
Hoop, Marcus.
Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins.
Degree: 2014, ETH Zürich
URL: http://hdl.handle.net/20.500.11850/179875
Subjects/Keywords: Gene Delivery
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hoop, M. (2014). Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins. (Thesis). ETH Zürich. Retrieved from http://hdl.handle.net/20.500.11850/179875
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hoop, Marcus. “Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins.” 2014. Thesis, ETH Zürich. Accessed January 25, 2021.
http://hdl.handle.net/20.500.11850/179875.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hoop, Marcus. “Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins.” 2014. Web. 25 Jan 2021.
Vancouver:
Hoop M. Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins. [Internet] [Thesis]. ETH Zürich; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/20.500.11850/179875.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hoop M. Modulation of the transduction of pseudotyped lentiviral vectors and their application for the production of recombinant proteins. [Thesis]. ETH Zürich; 2014. Available from: http://hdl.handle.net/20.500.11850/179875
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Louisiana State University
16.
Landry, Corey Raymond.
An Exploration of Plasmonics for Nanoparticle-based Gene Delivery.
Degree: MSBAE, Engineering, 2015, Louisiana State University
URL: etd-07082015-135301
;
https://digitalcommons.lsu.edu/gradschool_theses/1167
► The spatiotemporal control of biological processes, especially cell growth and differentiation, remains one of the most compelling challenges in basic and clinical biomedical research.…
(more)
▼ The spatiotemporal control of biological processes, especially cell growth and differentiation, remains one of the most compelling challenges in basic and clinical biomedical research. Fields as diverse as cancer therapy and regenerative medicine rely on spatial and temporal control of biochemical cues to achieve desired biological objectives. MicroRNA are attractive for highly-localized delivery applications because their instability in the cell restricts their biological effect to a small target area. These short, non-coding strands can be easily synthesized and modified for attachment and release from nanoparticle delivery vehicles. The research interest around microRNA therapies has produced a wide array of pathways dependent on microRNA, especially in osteogenesis, adipogenesis, and cancer therapy. The development of a versatile delivery platform will complement the wide array of microRNA pathways that are being discovered. The unique optical properties of metal nanoparticles provide a powerful tool for microRNA delivery via photochemical or photothermal methods. The plasmonic response of silver and gold particles provide an important complement to microRNAs with photocleavable linking moieties, where the coherent oscillation of electrons at specific wavelengths may be able to greatly enhance delivery efficiency while providing non-invasive external control of release.
Subjects/Keywords: microRNA; Nanoparticles; Plasmonics; Gene Delivery
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APA (6th Edition):
Landry, C. R. (2015). An Exploration of Plasmonics for Nanoparticle-based Gene Delivery. (Masters Thesis). Louisiana State University. Retrieved from etd-07082015-135301 ; https://digitalcommons.lsu.edu/gradschool_theses/1167
Chicago Manual of Style (16th Edition):
Landry, Corey Raymond. “An Exploration of Plasmonics for Nanoparticle-based Gene Delivery.” 2015. Masters Thesis, Louisiana State University. Accessed January 25, 2021.
etd-07082015-135301 ; https://digitalcommons.lsu.edu/gradschool_theses/1167.
MLA Handbook (7th Edition):
Landry, Corey Raymond. “An Exploration of Plasmonics for Nanoparticle-based Gene Delivery.” 2015. Web. 25 Jan 2021.
Vancouver:
Landry CR. An Exploration of Plasmonics for Nanoparticle-based Gene Delivery. [Internet] [Masters thesis]. Louisiana State University; 2015. [cited 2021 Jan 25].
Available from: etd-07082015-135301 ; https://digitalcommons.lsu.edu/gradschool_theses/1167.
Council of Science Editors:
Landry CR. An Exploration of Plasmonics for Nanoparticle-based Gene Delivery. [Masters Thesis]. Louisiana State University; 2015. Available from: etd-07082015-135301 ; https://digitalcommons.lsu.edu/gradschool_theses/1167
17.
Abe, Hiroyuki.
Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。.
Degree: 博士(医学), 2016, Niigata University / 新潟大学
URL: http://hdl.handle.net/10191/41892
► 学位の種類: 博士(医学). 報告番号: 甲第4097号. 学位記番号: 新大院博(医)甲第664号. 学位授与年月日: 平成28年3月23日
Molecular Therapy—Nucleic Acids. 2016, 5, e276.
Liver fibrosis is the final stage of liver diseases that lead…
(more)
▼ 学位の種類: 博士(医学). 報告番号: 甲第4097号. 学位記番号: 新大院博(医)甲第664号. 学位授与年月日: 平成28年3月23日
Molecular Therapy—Nucleic Acids. 2016, 5, e276.
Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ~5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.
Subjects/Keywords: gene therapy; hydrodynamic gene delivery; liver cirrhosis; MMP13; nucleic acids delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Abe, H. (2016). Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。. (Thesis). Niigata University / 新潟大学. Retrieved from http://hdl.handle.net/10191/41892
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Abe, Hiroyuki. “Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。.” 2016. Thesis, Niigata University / 新潟大学. Accessed January 25, 2021.
http://hdl.handle.net/10191/41892.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Abe, Hiroyuki. “Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。.” 2016. Web. 25 Jan 2021.
Vancouver:
Abe H. Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。. [Internet] [Thesis]. Niigata University / 新潟大学; 2016. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10191/41892.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Abe H. Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model : ハイドロダイナミック法によるマトリックスメタロプロテアーゼ-13遺伝子の肝特異的遺伝子導入はラット肝硬変モデルにおける肝線維化予防に有用である。. [Thesis]. Niigata University / 新潟大学; 2016. Available from: http://hdl.handle.net/10191/41892
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Iowa
18.
Duskey, Jason Thomas.
The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery.
Degree: PhD, Pharmacy, 2013, University of Iowa
URL: https://ir.uiowa.edu/etd/4965
► The ability to deliver DNA to target cells creating therapeutic effects remains an important goal in the field of gene therapy. A majority of…
(more)
▼ The ability to deliver DNA to target cells creating therapeutic effects remains an important goal in the field of
gene therapy. A majority of clinical trials to overcome this issue have utilized viral vectors due to their efficiency at DNA
delivery and ability to create high levels of
gene expression. However, their inherent toxicity and a several clinical trials leading to patients contracting new diseases from the treatment have greatly hindered the progress of viral
gene therapy. Non-viral
gene delivery agents have a much better safety profile, but are also much less efficient at delivering DNA, leading to low
gene expression. The reason for this low expression is the numerous barriers that must be overcome to achieve
gene expression: circulation, tissue specific accumulation, internalization, release of DNA cargo, and nuclear localization. While peptides are currently being improved upon, enhancing binding and the ability to protect DNA, they are still deficient when it comes to tissue specificity. Numerous targeting methods, including the use of lectins, antibodies, aptamers, and peptides, have been designed to deliver molecules to a specific research. Research to incorporate targeting ligands onto non-viral
gene delivery vectors is abundant in the literature; however, successful site specific
gene delivery has not been achieved.
The somatostatin receptor 2 (SSTR2) ligand, octreotide, is a well-researched eight amino acid peptide that has extensive SAR data available. Also, the receptors have been well characterized and octreotide is used clinically in the radioscintigraphy imaging of brain tumors. While well researched, there are unexplored opportunities to utilize octreotide to enhance non-viral
gene delivery vectors.
The overall scope of this thesis is to develop and synthesize non-viral
gene delivery peptides conjugated to octreotide creating receptor mediated targeting of DNA polyplexes to create tissue specific accumulation. Initial experiments indicated that attachment of octreotide to the polycationic peptide WK
18 does not inhibit affinity for the SSTR2 receptor. Therefore, peptides were designed and synthesized to attach octreotide onto polyacridine peptide (Acr-Lys)
6. Polyplex characteristics were unchanged by the incorporation of octreotide, and exhibited very low genotoxic effects compared to the in vitro
gene delivery agent PEI. Competitive binding assays suggested a stoichiometric, ligand, and temperature dependent accumulation of polyplex on SSTR2 expressing cells, but
gene expression could not be achieved.
The success of (Acr-Lys)6octreotide, led to the synthesis of a di-maleimide-PEG attached to each end by (Acr-Lys
4)
3Acr-Lys-Cys or Cys-Gly
5octreotide in attempts to create distance, and better ligand availability for the receptor, by expressing octreotide away from the polyplex. Testing of this peptide in PEGylated polyplex ad-mixtures verified that separating the DNA binding peptide from octreotide did lead to better…
Advisors/Committee Members: Rice, Kevin G. (supervisor).
Subjects/Keywords: Gene Delivery; Non-Viral Gene Delivery; Octreotide; Pharmacy and Pharmaceutical Sciences
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Duskey, J. T. (2013). The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/4965
Chicago Manual of Style (16th Edition):
Duskey, Jason Thomas. “The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery.” 2013. Doctoral Dissertation, University of Iowa. Accessed January 25, 2021.
https://ir.uiowa.edu/etd/4965.
MLA Handbook (7th Edition):
Duskey, Jason Thomas. “The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery.” 2013. Web. 25 Jan 2021.
Vancouver:
Duskey JT. The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery. [Internet] [Doctoral dissertation]. University of Iowa; 2013. [cited 2021 Jan 25].
Available from: https://ir.uiowa.edu/etd/4965.
Council of Science Editors:
Duskey JT. The development and biological evaluation of Octreotide contatining peptides for receptor mediated non-viral gene delivery. [Doctoral Dissertation]. University of Iowa; 2013. Available from: https://ir.uiowa.edu/etd/4965
19.
Tzeng, Stephany Yi.
Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/36968
► The fields of biomaterials, nanobiotechnology, and gene and drug delivery have all progressed over the past decades and have rapidly become a focus of research…
(more)
▼ The fields of biomaterials, nanobiotechnology, and
gene and drug
delivery have all progressed over the past decades and have rapidly become a focus of research for many applications. In particular,
gene delivery, with cargoes including DNA, small interfering RNA (siRNA), and short hairpin RNA (shRNA), is a very attractive tool for research purposes as well as clinical application. The ability to change a cell's expression at the genetic level affords researchers great flexibility in studying a cell's behavior in relation to its
gene expression in a laboratory setting. More translational applications for which
gene therapy can be a useful tool include cancer therapy and regenerative medicine. For the latter, cells must be directed to grow or behave in strictly defined mann;ers, an issue that is often addressed via administration of soluble factors or spatial or mechanical cues during the cell culture period. While these are by no means strategies to be disregarded,
cells can be guided more directly using
gene therapy. For example, in some cases, stem cell differentiation is controlled primarily by or inhibited by known factors. While designing drugs to target the specific proteins of interest is dependent on protein structure as well as the ability to deliver the drug, knowing the
gene sequence could allow us to deliver or suppress the
gene directly, bypassing undruggable protein targets. In the case of disease treatment, many diseases, including inherited and some acquired diseases like cancer, are genetic in origin or are affected by the patient's genetic background. The biodegradable polymer nanoparticles we have designed are able to combat such diseases by changing the
gene expression of cancer cells, such as by decreasing their expression of survival factors or causing them to overexpress apoptotic factors that cause cell death. Unlike traditionally studied viral methods, our synthetic nanoparticle system avoids many of the safety concerns
surrounding viruses, including toxicity, severe inflammatory or immune response, and the potential for insertional mutagenesis. Non-viral
gene delivery is an exceedingly versatile tool; as will be shown below, many types of therapeutic nucleic acids can be delivered using our polymers, and once
delivery to a given cell type is optimized, the sequence of the genes being delivered do not affect the properties of the nanoparticles, therefore allowing for essentially any
gene to be delivered using our system. Poly(β-amino ester)s (PBAEs), a newer class of biomaterials effective in
gene delivery, have been developed for DNA and siRNA
delivery to human GBM cells. Importantly, specific chemical structures that have a strong effect on
delivery of one nucleic acid type over the other have been identified, and overall trends in polymer structures have been correlated with transfection efficacy. PBAEs that can transfect 2-D and 3-D brain cancer cultures while having minimal effect on fetal
brain cells have also been found. This phenomenon was verified in a different species and tissue…
Advisors/Committee Members: Quinones-Hinojosa, Alfredo (advisor).
Subjects/Keywords: nanomedicine;
nanoparticles;
polymeric gene delivery;
non-viral gene delivery;
DNA delivery;
siRNA delivery;
targeted cancer therapy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tzeng, S. Y. (2014). Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/36968
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tzeng, Stephany Yi. “Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering.” 2014. Thesis, Johns Hopkins University. Accessed January 25, 2021.
http://jhir.library.jhu.edu/handle/1774.2/36968.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tzeng, Stephany Yi. “Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering.” 2014. Web. 25 Jan 2021.
Vancouver:
Tzeng SY. Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Jan 25].
Available from: http://jhir.library.jhu.edu/handle/1774.2/36968.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tzeng SY. Polymeric Nanoparticle-Based DNA AND siRNA Delivery for Cancer Treatment and Stem Cell Engineering. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/36968
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley
20.
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 (6th 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 (16th Edition):
Bai, Yong. “In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent.” 2010. Thesis, University of California – Berkeley. Accessed January 25, 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 (7th Edition):
Bai, Yong. “In vivo Delivery of Catalytic RNase P Ribozyme as an Antiviral Agent.” 2010. Web. 25 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 25].
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 Utah
21.
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 (6th 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 (16th Edition):
Christensen, Lane. “Reducible poly(amido ethylenimine)s for gene delivery;.” 2007. Doctoral Dissertation, University of Utah. Accessed January 25, 2021.
http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/1611/rec/1085.
MLA Handbook (7th Edition):
Christensen, Lane. “Reducible poly(amido ethylenimine)s for gene delivery;.” 2007. Web. 25 Jan 2021.
Vancouver:
Christensen L. Reducible poly(amido ethylenimine)s for gene delivery;. [Internet] [Doctoral dissertation]. University of Utah; 2007. [cited 2021 Jan 25].
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

University of Alberta
22.
Ahmed, M.
Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy.
Degree: PhD, Department of Chemical and Materials
Engineering, 2012, University of Alberta
URL: https://era.library.ualberta.ca/files/k930bz38z
► The study provides a comprehensive account on the development of novel synthetic carbohydrate and phosphorylcholine polymer based gene delivery vectors. Since the development and use…
(more)
▼ The study provides a comprehensive account on the
development of novel synthetic carbohydrate and phosphorylcholine
polymer based gene delivery vectors. Since the development and use
of first non-viral vector for gene delivery applications, a wide
range of polymers have been synthesized and studied for their gene
delivery efficacies. With the advent of living radical
polymerization, well-defined polymers with varying molecular
weights, compositions and architectures have been synthesized and
evaluated as potent gene delivery vectors. Reversible
addition-fragmentation chain transfer polymerization (RAFT) has
allowed the facile synthesis of tailor-made cationic polymers which
are promising non-viral gene delivery vectors. Advanced
structure-activity relationship studies between the polymers and
gene expression have been possible due to the remarkable control in
the design of these polymers via the RAFT process. In the first
study, RAFT polymerization technique allows the successful
synthesis of cationic glycopolymers containing pendant sugar
moieties. A library of cationic glycopolymers of pre-determined
molar masses and narrow polydispersities ranging from 3-30 kDa has
been synthesized. These polymers differ from each other in their
architectures (block versus random), molecular weights, and monomer
ratios (carbohydrate to cationic segment). It is shown that the
above-mentioned parameters can largely affect the toxicity, DNA
condensation ability and gene delivery efficacy of these polymers.
The effect of serum proteins on statistical and diblock copolymer
based polyplexes and hence gene delivery efficacy is further
studied. In the second study, 2-methacryloxyethyl phosphorylcholine
(MPC) copolymers are studied for their ability to produce non-toxic
and biocompatible materials. The cationic MPC copolymers of varying
architectures (block versus random) are produced by RAFT
polymerization technique. The copolymers produced are further
evaluated for their, morphology, cellular uptake and gene delivery
efficacy in the presence and absence of serum. The polymers with
branched architecture are reported to be superior gene delivery
vectors as compared to their linear analogues. In another study,
hyperbranched glycopolymers of varying molecular weights and
compositions are synthesized via reversible addition fragmentation
chain transfer (RAFT) process and are further explored for their
gene expression in vitro. Galactose based hyperbranched polymers
are compared to glucose-derived hyperbranched polymers for their
cellular uptake, toxicity, lectin interactions and gene expression.
Furthermore, the cellular uptake and gene expression are studied in
two different cell lines in the presence of lectins. The superior
gene expression of linear statistical polymers is also accompanied
by their significant aggregation in serum containing media. To
solve this problem, carbohydrate and phosphorylcholine based
cationic polymers having a novel architecture, different
compositions and varying molecular weights are produced and are
termed as…
Subjects/Keywords: Cationic Glycopolymers; Gene delivery; RAFT polymerization
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ahmed, M. (2012). Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/k930bz38z
Chicago Manual of Style (16th Edition):
Ahmed, M. “Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy.” 2012. Doctoral Dissertation, University of Alberta. Accessed January 25, 2021.
https://era.library.ualberta.ca/files/k930bz38z.
MLA Handbook (7th Edition):
Ahmed, M. “Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy.” 2012. Web. 25 Jan 2021.
Vancouver:
Ahmed M. Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy. [Internet] [Doctoral dissertation]. University of Alberta; 2012. [cited 2021 Jan 25].
Available from: https://era.library.ualberta.ca/files/k930bz38z.
Council of Science Editors:
Ahmed M. Carbohydrate and Phosphorylcholine based Polymers Prepared
by Reversible Addition-Fragmentation Chain Transfer Polymerization
for Gene Therapy. [Doctoral Dissertation]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/k930bz38z

Cornell University
23.
Wu, Jun.
L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds.
Degree: PhD, Biomedical Engineering, 2011, Cornell University
URL: http://hdl.handle.net/1813/33553
► A family of water soluble and positively charged L-arginine based poly (ester amide)s (Arg-PEAs) was synthesized by solution polycondensation. These biodegradable Arg-PEAs consist of 3…
(more)
▼ A family of water soluble and positively charged L-arginine based poly (ester amide)s (Arg-PEAs) was synthesized by solution polycondensation. These biodegradable Arg-PEAs consist of 3 nontoxic building blocks: L-arginine, diols and dicarboxylic acids. The Arg-PEAs were prepared by the reaction of tetra-p- toluenesulfonic acids salts of bis-(L-arginine) [alpha], [omega]-alkylene diesters and di-pnitrophenyl esters of dicarboxylic acids. Optimal conditions of the monomers and polymers synthesis were investigated, and the monomers and Arg-PEAs were chemically characterized. Arg-PEAs were found to have good solubility in water and many other polar solvents. . Arg-PEAs were evaluated by many biological assays for the
gene delivery applications. Structure-function relationship of the Arg-PEAs revealed that changing the number of methylene groups in the diol or/and diacid segment could finely tune the hydrophobic and cationic properties of the Arg-PEAs, and then affect the
gene delivery efficiency. MTT assay showed that all the prepared Arg-PEAs and Arg-PEA/DNA complexes were non-toxic to the cell lines even at very large doses. Some of Arg-PEAs showed comparable or higher transfection efficiency than the commercial transfection agents, Superfect® and Lipofectamine2000®. Based on the above results, a new generation of Arg-PEAs, oligoethylene glycols and L-arginine based poly (ether ester amide)s (Arg-PEEAs) were developed. The new Arg-PEEAs had more flexible chain due to the introduction of oligoethylene glycols. Structure-function relationship of the Arg-PEEAs was intensively studied. MTT assay showed that all the and Arg-PEEA/DNA complexes were non-toxic to the cell lines, primary cells and stem cells even at very large doses. The Arg-PEEAs expanded the
gene transfection from cell lines to primary cells/stem cells, and showed comparable or higher transfection efficiency than the commercial transfection agents, Superfect® and Lipofectamine2000®. Arg-PEAs with double bond functionality (Arg-UPEAs) could be photocrosslinked with Pluronic- diacrylate (Pluronic-DA) to form cationic hybrid hydrogels. The physicochemical and mechanical properties of the hybrid hydrogels were studied. The fibroblast and endothelial cells were cultured on the hybrid hydrogel surface and inside the hydrogel, respectively. The results indicated that the introduction of ArgUPEAs could significantly increase the cell attachment performance on hydrogel surface and viability inside the hydrogel. Some new L-phenylalanine based poly (ester amide)s (Phe-PEA) or derivatives were developed as the coating materials causing low inflammatory response. One example is the block copolymer of Phe-PEA and poly ([epsilon] -caprolactone) (PCL) [PEAb-PCL], another example is the L-Arginine and L-phenylalanine based hybrid poly (ester amide)s (Arg-Phe-PEAs). The new biomaterials were characterized and studied the cellular responses, such as cell attachment and macrophage inflammatory response. The results indicated that they could promote the cell attachment and cause…
Advisors/Committee Members: Chu, Chih-Chang (chair), Collins, Ruth N. (committee member), Bonassar, Lawrence (committee member).
Subjects/Keywords: Arginine; Poly (ester amide); Gene delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wu, J. (2011). L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33553
Chicago Manual of Style (16th Edition):
Wu, Jun. “L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds.” 2011. Doctoral Dissertation, Cornell University. Accessed January 25, 2021.
http://hdl.handle.net/1813/33553.
MLA Handbook (7th Edition):
Wu, Jun. “L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds.” 2011. Web. 25 Jan 2021.
Vancouver:
Wu J. L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/1813/33553.
Council of Science Editors:
Wu J. L-Arginine And L-Phenylalanine Based Poly (Ester Amide)S, Their Synthesis, Characterization, Formulations And Applications As Gene Delivery Vectors And Tissue Engineering Scaffolds. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33553

University of Waterloo
24.
Calderon-nieva, Daniella.
Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.
Degree: 2018, University of Waterloo
URL: http://hdl.handle.net/10012/12812
► Cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG-ODN) are nucleotide sequence motifs found in the bacterial genome that activate the mammalian innate immune response and have been found to boost…
(more)
▼ Cytosine-phosphodiester-guanine oligodeoxynucleotides (CpG-ODN) are nucleotide sequence motifs found in the bacterial genome that activate the mammalian innate immune response and have been found to boost humoral immunity when used as vaccine adjuvants in non-human primates and mice [1, 2]. Although species specific differences exist in the nature of the response, CpG-ODN can also activate chicken innate immune cells through the Toll-like receptor 21 (TLR 21) and has been found to protect against common bacterial infections in chickens such as Escherichia coli (E. coli) in neonatal broiler chicks after spray administration. The importance of CpG-ODN application is that the Canadian chicken industry voluntarily agreed to withdraw the prophylactic use of Category I antibiotics in poultry, which leaves chicks highly susceptible to infection and can result in high mortality rates and large economic losses.
Owing to the relatively low manufacturing cost, and ease of customization of oligonucleotides [3], CpG-ODN administration is a highly attractive strategy against E. coli infection in neonatal broiler chicks. Especially because the development of a non-species-specific E. coli vaccine is difficult due to the genetic variation of E. coli.
The objective of this thesis was to develop an inhalable nanoparticle CpG-ODN formulation that is superior to CpG-ODN on its own. Ultimately, the goal is to develop an inhalable nanoparticle carrier that can protect CpG-ODN, enhance innate immune stimulation, and prolong the protective effects in broiler chicks.
In practice, oligonucleotides are highly susceptible to degradation in biological environments. Moreover, in the lung, mucociliary clearance and enzymatic clearance play a role in preventing optimal immune stimulation and delivery of the vaccine to immune “hot spots”. In the human lung, bio-adhesive polymers have shown to improve DNA delivery by increasing residence time in mucosal membranes.
Gemini surfactant nanoparticles (NPs) are a novel nucleic acid delivery system that could deliver CpG-ODN to important innate immune activating cells for an optimal immune-protective effect. Bio adhesive polymers such as chitosan and polyvinylpyrolidone could also improve delivery of DNA to the lung. This work investigated how the physicochemical properties of nebulized bio adhesive polymer nanoparticle formulations influence delivery of the vaccine to the avian lung and activation of the innate immune response in comparison to CpG-ODN on its own.
The dicationic gemini surfactants 12-3-12, 16-3-16, and 18-3-18 were used in combination with a phospholipid (DPPC), and different bio adhesive polymers to prepare various types of hybrid nanoparticles and assess their transfection efficiency in a chicken macrophage immortal cell line HD11. The transfection efficiency and toxicity of formulations was measured using flow cytometry. All formulations were also assessed in their capability to induce an innate immune response in HD11 cells by quantitating nitrite (nitric oxide) production using…
Subjects/Keywords: Nanotechnology; Gene delivery; Vaccine; Nanoparticle; Veterinary
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Calderon-nieva, D. (2018). Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/12812
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Calderon-nieva, Daniella. “Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.” 2018. Thesis, University of Waterloo. Accessed January 25, 2021.
http://hdl.handle.net/10012/12812.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Calderon-nieva, Daniella. “Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens.” 2018. Web. 25 Jan 2021.
Vancouver:
Calderon-nieva D. Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. [Internet] [Thesis]. University of Waterloo; 2018. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10012/12812.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Calderon-nieva D. Improving the delivery and immunogenicity of an inhalable CpG-ODN DNA vaccine by bio-adhesive gemini nanoparticles in neonatal chickens. [Thesis]. University of Waterloo; 2018. Available from: http://hdl.handle.net/10012/12812
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal
25.
Ndzama, Nwabisa Florence.
The effects of fiscal policy on the current account and real exchange rate in South Africa.
Degree: 2015, University of KwaZulu-Natal
URL: http://hdl.handle.net/10413/16061
► This dissertation empirically studies the effects of expansionary fiscal policy on the current account and the real exchange rate in the South African economy. Recursive…
(more)
▼ This dissertation empirically studies the effects of expansionary fiscal policy on the current account and the real exchange rate in the South African economy. Recursive vector auto-regressive models based on the Choleski factorization identification scheme are used in the empirical analysis. This identification approach requires the imposition of restrictions on the VAR model and the most endogenous variables are ordered last. The dissertation uses quarterly data for the period 1990:1 to 2014:4 which was collected from the South African Reserve Bank website and the World Development Indicators.
A 5-variable reduced form VAR model is used to generate various impulse response functions (which show the response of other variables to a shock to one variable), to carry out a variance decomposition (to assess how much variation in one variable is caused by another variable’s error term) and to conduct Granger causality tests (to assess whether each variable Granger causes, or is caused by, each other variable). The variables examined are: the government budget deficit (GOV), the current account (CUR) (both measured as percentage of GDP), the logged real exchange rate (LREER), logged real GDP (LRGDP) and the 3–month real interest rate (RIR).
The current literature is quite inconclusive about the relationships between the government budget deficit, the current account and the real exchange rate and is generally focused on developed countries, in particular the United States. This dissertation contributes to the literature from a South African perspective. In spite of concerns about “twin deficits” (that is, when the fiscal deficit increases, the current account deficit worsens) for the South African economy, empirical evidence indicates that “twin divergence” is a more usual feature of historical data. In contrast to most of the theoretical models, the results for the South African economy suggest that an expansionary fiscal policy shocks improves the current account, depicting “twin divergence”. The effects of fiscal deficits on the real exchange rate seem to be consistent with the conventional view, that a government budget deficit induces a real exchange rate appreciation. The “twin divergence” of fiscal policy and the current account is also explained by the greater prevalence of output shocks than fiscal shocks.
Advisors/Committee Members: Fairburn, James A. (advisor).
Subjects/Keywords: Fluc-mRNA.; Gold nanoparticles.; Vitro.; Gene delivery.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ndzama, N. F. (2015). The effects of fiscal policy on the current account and real exchange rate in South Africa. (Thesis). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/16061
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ndzama, Nwabisa Florence. “The effects of fiscal policy on the current account and real exchange rate in South Africa.” 2015. Thesis, University of KwaZulu-Natal. Accessed January 25, 2021.
http://hdl.handle.net/10413/16061.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ndzama, Nwabisa Florence. “The effects of fiscal policy on the current account and real exchange rate in South Africa.” 2015. Web. 25 Jan 2021.
Vancouver:
Ndzama NF. The effects of fiscal policy on the current account and real exchange rate in South Africa. [Internet] [Thesis]. University of KwaZulu-Natal; 2015. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10413/16061.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ndzama NF. The effects of fiscal policy on the current account and real exchange rate in South Africa. [Thesis]. University of KwaZulu-Natal; 2015. Available from: http://hdl.handle.net/10413/16061
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Durham University
26.
Welsh, Simon.
Towards the controlled destabilisation of aggregates.
Degree: PhD, 2002, Durham University
URL: http://etheses.dur.ac.uk/3136/
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632
► Lipid based non-viral delivery systems are potentially of great importance to the development of an effective and versatile therapeutic gene treatment. Many difficulties are faced…
(more)
▼ Lipid based non-viral delivery systems are potentially of great importance to the development of an effective and versatile therapeutic gene treatment. Many difficulties are faced in designing efficient lipid based gene delivery systems and addressing the problem of endosomal escape is one key area where efficiency could be greatly improved Molecules aimed at inducing aggregate disruption in response to changes in pH, or metal ion concentration, have been synthesised. Series of compounds were prepared based on cationic 5-alkyl-2-methylaminoalkyl pyridine amphiphiles and amphiphilic C(_8)-C(_16) EDTA dialkylamides. The critical aggregation concentration of each species was measured and a series of experiments undertaken, designed to assess the extent of pH, or metal ion concentration, induced aggregate disruption effects. The experiments were carried out by including the molecules to be examined as small mole percent co-aggregates in micellar and liposome model systems. Each group of compounds appears to exhibit disruption effects on the more strongly ordered bilayer membrane systems, with the EDTA based compounds displaying the most consistent pH dependent disruption. However, the more dynamic micellar aggregate models were less sensitive to disruption using the particular observation method employed.
Subjects/Keywords: 616; Gene delivery
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Welsh, S. (2002). Towards the controlled destabilisation of aggregates. (Doctoral Dissertation). Durham University. Retrieved from http://etheses.dur.ac.uk/3136/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632
Chicago Manual of Style (16th Edition):
Welsh, Simon. “Towards the controlled destabilisation of aggregates.” 2002. Doctoral Dissertation, Durham University. Accessed January 25, 2021.
http://etheses.dur.ac.uk/3136/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632.
MLA Handbook (7th Edition):
Welsh, Simon. “Towards the controlled destabilisation of aggregates.” 2002. Web. 25 Jan 2021.
Vancouver:
Welsh S. Towards the controlled destabilisation of aggregates. [Internet] [Doctoral dissertation]. Durham University; 2002. [cited 2021 Jan 25].
Available from: http://etheses.dur.ac.uk/3136/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632.
Council of Science Editors:
Welsh S. Towards the controlled destabilisation of aggregates. [Doctoral Dissertation]. Durham University; 2002. Available from: http://etheses.dur.ac.uk/3136/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268632

National University of Ireland – Galway
27.
Shane, Browne.
A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
.
Degree: 2014, National University of Ireland – Galway
URL: http://hdl.handle.net/10379/4927
► Tissue engineered organs and implants hold promise for the replacement of damaged and diseased organs. However, the foreign body response (FBR) is a major obstacle…
(more)
▼ Tissue engineered organs and implants hold promise for the replacement of damaged and diseased organs. However, the foreign body response (FBR) is a major obstacle that compromises the function of tissue engineered constructs, typically causing them to fail. Two components of the FBR are the inflammatory response and a lack of vascularization. To overcome these, this project has delivered anti-inflammatory and pro-angiogenic nucleic acids. A collagen system was developed to release interleukin-6 (IL-6) siRNA and endothelial nitric oxide synthase (eNOS) pDNA in a staggered manner. Collagen hollow microspheres were fabricated using a template-method and displayed an ability to load and release pDNA, maintaining the capability to transfect 3T3 fibroblasts in vitro, while reducing vector-associated toxicity. Following the identification of an optimal microsphere size, hollow collagen microspheres were assembled into a collagen sphere-in-hydrogel system that displayed a staggered release profile in vitro This system was assessed in vivo in a subcutaneous rat model. The doses of IL-6 siRNA and eNOS pDNA were first individually optimized for their ability to reduce the volume fraction of inflammatory cells (7 days) and increase the length density of blood vessels (14 days), respectively. The identified optimal doses were combined and the ability of the system to decrease the volume fraction of inflammatory cells and increase the length density of blood vessels was confirmed at both 7 and 14 days. Analysis of the tissue using Raman spectroscopy revealed that in addition to changes in inflammation and angiogenesis, there were also changes in the extracellular matrix (ECM) of the tissue at seven days. While changes in sulfated glycosaminoglycans (sGAG) content of the ECM were not detected, changes in the binding of sGAG of the ECM to growth factors was observed. Two growth factors tested, VEGF165 and bFGF showed increased binding to sGAG extracted from eNOS pDNA treated samples at seven days, increasing the angiogenic potential of the ECM. Overall, the system shows promise for the treatment of pathologies in which inflammation and angiogenesis are dysregulated.
Advisors/Committee Members: Pandit, Abhay (advisor).
Subjects/Keywords: Biomaterials;
Gene delivery;
Inflammation;
Angiogenesis;
Extracellular matrix
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shane, B. (2014). A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
. (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/4927
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shane, Browne. “A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
.” 2014. Thesis, National University of Ireland – Galway. Accessed January 25, 2021.
http://hdl.handle.net/10379/4927.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shane, Browne. “A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
.” 2014. Web. 25 Jan 2021.
Vancouver:
Shane B. A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
. [Internet] [Thesis]. National University of Ireland – Galway; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/10379/4927.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shane B. A multi-modal collagen nucleic acid delivery system for the modulation of inflammation and promotion of angiogenesis
. [Thesis]. National University of Ireland – Galway; 2014. Available from: http://hdl.handle.net/10379/4927
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
28.
Mcclellan, Annie Katherine.
Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles.
Degree: M.S. in Engineering Science, Chemical Engineering, 2016, University of Mississippi
URL: https://egrove.olemiss.edu/etd/398
► Since the development of gene therapy, a variety of non-viral nucleic acid delivery vehicles have been prepared and studied for their transfection efficiencies. Recently, polymeric…
(more)
▼ Since the development of
gene therapy, a variety of non-viral nucleic acid
delivery vehicles have been prepared and studied for their transfection efficiencies. Recently, polymeric
gene delivery vehicles have gained popularity for their low immunogenicity and high transfection efficiency. With the advent of controlled radical polymerization (CRP) and more specifically reversible addition-fragmentation chain transfer (RAFT) polymerization, it is now possible to develop well-defined polymers with predicted molecular weights and architectures. The work presented here focuses on the RAFT polymerization of a family of amphiphilic, cationic copolymers to be utilized for nucleic acid
delivery. These copolymers are composed of a stabilizing hydrophilic block of oligo(ethylene glycol) methyl ether methacrylate (OEMGA) and a cationic, endosomolytic block of 2-(dimethylamino) ethyl methacrylate (DMAEMA), 2-(diethylamino) ethyl methacrylate (DEAEMA), or 2-(diisopropylamino) ethyl methacrylate (DPAEMA). The hydrophilic content of this copolymer series was kept constant while the degrees of polymerization of the cationic block of 25, 50, and 75 were targeted to elucidate the effects of tertiary amine functionalization on
gene delivery efficacy. Means of characterization included gel permeation chromatography (GPC), dynamic light scattering (DLS), electrophoresis, and in vitro
gene expression and toxicity studies. As a result from this study, our findings indicate the significance of cationic group functionalization on siRNA
delivery, and the pH-responsive nucleic acid
delivery vehicles synthesized show promise for future studies of nucleic acid
delivery.
Advisors/Committee Members: Adam E. Smith, John O'Haver, Tracy A. Brooks.
Subjects/Keywords: Gene Delivery; Ph-Responsive; Raft; Polymer Chemistry
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mcclellan, A. K. (2016). Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles. (Thesis). University of Mississippi. Retrieved from https://egrove.olemiss.edu/etd/398
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mcclellan, Annie Katherine. “Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles.” 2016. Thesis, University of Mississippi. Accessed January 25, 2021.
https://egrove.olemiss.edu/etd/398.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mcclellan, Annie Katherine. “Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles.” 2016. Web. 25 Jan 2021.
Vancouver:
Mcclellan AK. Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles. [Internet] [Thesis]. University of Mississippi; 2016. [cited 2021 Jan 25].
Available from: https://egrove.olemiss.edu/etd/398.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mcclellan AK. Raft Polymerization Of Ph-Responsive, Diblock Copolymers For Nucleic Acid Delivery Vehicles. [Thesis]. University of Mississippi; 2016. Available from: https://egrove.olemiss.edu/etd/398
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign
29.
Zhang, Rujing.
Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities.
Degree: MS, 0130, 2014, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/46865
► The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. This thesis aims to report…
(more)
▼ The rational design of effective and safe non-viral
gene vectors is largely dependent on the understanding of the structure-property relationship. This thesis aims to report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and to mechanistically unravel the effect of polypeptide structure on the
gene delivery capability. Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities. Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent LipofectamineTM 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral
gene delivery vectors, and the top-performing materials identified also serve as promising additions to the existing systems.
Advisors/Committee Members: Cheng, Jianjun (advisor).
Subjects/Keywords: polypeptides; gene delivery; guanidine; helical structure
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, R. (2014). Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities. (Thesis). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/46865
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhang, Rujing. “Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities.” 2014. Thesis, University of Illinois – Urbana-Champaign. Accessed January 25, 2021.
http://hdl.handle.net/2142/46865.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhang, Rujing. “Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities.” 2014. Web. 25 Jan 2021.
Vancouver:
Zhang R. Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities. [Internet] [Thesis]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/2142/46865.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhang R. Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities. [Thesis]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/46865
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign
30.
Xu, Qingxing Noel.
Coaxial double-walled microspheres for drug and gene delivery applications.
Degree: PhD, 0300, 2014, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/49760
► Polymeric double-walled microspheres were developed by coaxial electrohydrodynamic atomization (CEHDA) and precision particle fabrication (PPF) techniques. Here, we focus on double-walled microspheres consisting of a…
(more)
▼ Polymeric double-walled microspheres were developed by coaxial electrohydrodynamic atomization (CEHDA) and precision particle fabrication (PPF) techniques. Here, we focus on double-walled microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) or poly(L-lactic acid) (PLLA) shell layer.
The first study involves bridging the experimental work on the fabrication of double-walled microspheres from CEHDA and the simulation work on the generation of compound droplets from the same process. Process conditions and solution parameters were investigated to ensure the formation of double-walled microspheres with a doxorubicin-loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Numerical simulation of CEHDA process was performed based on a computational fluid dynamics (CFD) model in Fluent. The simulation results were compared with the experimental work to illustrate the capability of the CFD model to predict the production of consistent double-walled microspheres.
The second study involves drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin-loaded PLGA core surrounded by a PDLLA shell layer. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer.
The third study involves designing and evaluating double-walled microspheres loaded with chitosan-p53 nanoparticles (chi-p53,
gene encoding p53 tumor suppressor protein) and/or doxorubicin in the shell and core phases, respectively, for combined
gene therapy and chemotherapy. The microspheres were monodisperse with a mean diameter of 65 to 75 μm and uniform shell thickness of 8 to 17 μm. The encapsulation efficiency of doxorubicin was significantly higher when it was encapsulated alone compared to co-encapsulation with chi-p53. However, the encapsulation efficiency of chi-p53 was not affected by the presence of doxorubicin. As desired, chi-p53 was released first, followed by simultaneous release of chi-p53 and doxorubicin at a near zero-order rate. Next, the therapeutic efficiencies of doxorubicin and/or chi-p53 in microsphere formulations were compared to free drug(s) and evaluated in terms of growth inhibition, and cellular expression of tumor suppressor p53 and apoptotic caspase 3 proteins in human…
Advisors/Committee Members: Yang, Hong (advisor), Yang, Hong (Committee Chair), Kong, Hyun Joon (committee member), Xie, Jianping (committee member), Tong, Yen Wah (committee member).
Subjects/Keywords: Drug Delivery; Double-Walled Microspheres; Drug; Gene
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APA (6th Edition):
Xu, Q. N. (2014). Coaxial double-walled microspheres for drug and gene delivery applications. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/49760
Chicago Manual of Style (16th Edition):
Xu, Qingxing Noel. “Coaxial double-walled microspheres for drug and gene delivery applications.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 25, 2021.
http://hdl.handle.net/2142/49760.
MLA Handbook (7th Edition):
Xu, Qingxing Noel. “Coaxial double-walled microspheres for drug and gene delivery applications.” 2014. Web. 25 Jan 2021.
Vancouver:
Xu QN. Coaxial double-walled microspheres for drug and gene delivery applications. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Jan 25].
Available from: http://hdl.handle.net/2142/49760.
Council of Science Editors:
Xu QN. Coaxial double-walled microspheres for drug and gene delivery applications. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/49760
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