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Type: Theses
Title: Intracellular microenvironment responsive nanogels for gene delivery
Author: Zhang, Bingyang
Issue Date: 2015
School/Discipline: School of Chemical Engineering
Abstract: Gene therapy is a modern technology applied by using therapeutic nucleic acids to treat or prevent diseases. The therapeutic nucleic acids can either be expressed to recombinant proteins for disease treatments or correct the genetic mutations in gene therapy for the treatments of various diseases. However, the development of gene therapy is greatly impeded by the limitation of gene delivery systems. Delivery of gene to eukaryotic cells is a multi-step process. Several barriers including cell membrane, nuclear pore complex (NPC) and intracellular enzymes have inhibited the transfection efficiency of gene. Therefore, the exploring of safe and high efficient gene carriers is essential for the development of gene therapy. In this thesis, one of the widely studied cationic polymers, polyehtylenimine (PEI), was employed for modifications in the gene delivery application. High molecular weight PEI (HMW PEI) is able to perform high efficient gene transfection to eukaryotic cells due to its good buffering capacity. However, it also has high cytotoxicity to cells owing to its non-biodegradability and its molecular weight related high positive charge density. On the other hand, low molecular weight PEI (LMW PEI) such as PEI800 shows negligible cytotoxicity to cells, but has low transfection efficiency. In order to reduce the cytotoxicity of PEI-based gene carrier while keep or improve the transfection efficiency, two biodegradable PEI-based gene carriers have been designed and successfully synthesized. The physical and chemical properties of both synthetic carriers were measured. The gene delivery performances of both carriers were also evaluated against Hela and HEK 293 cells. The synthetic biodegradable gene carriers display good gene binding ability, low cytotoxicity and good buffering capacity. In addition, both carriers are able to perform gene transfection with high efficiency.
Advisor: Bi, Jingxiu
Dai, Sheng
Dissertation Note: Thesis (M.Phil.) (Research by Publication) -- University of Adelaide, School of Chemical Engineering, 2015.
Keywords: gene delivery
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
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