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Gene delivery

Rose, Laura C

Supervisor and department: Uludag, Hasan Chemical Engineering

Examining committee member and department: Unsworth, Larry Chemical Engineering Rice, Kevin Pharmaceutical Sciences and Experimental Therapeutics El-Bialy, Tarek Dentistry Burrell, Robert Biomedical Engineering Gorassini, Monica Biomedical Engineering Adesida, Adetola Surgery

Department: Department of Biomedical Engineering


Date accepted: 2013-11-13T15:29:32Z

Graduation date: 2014-06

Degree: Doctor of Philosophy

Degree level: Doctoral

Abstract: 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.

Language: English

DOI: doi:10.7939-R3QF8JR68

Rights: Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.

Autor: Rose, Laura C



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