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Polyethylene imine modified polysaccharide as a non-viral gene carrier
Dissertation

Polyethylene imine modified polysaccharide as a non-viral gene carrier

Peng, Yu-Shiang
Doctor of Philosophy (PHD), 國立清華大學, 化學工程學系
2013

Abstract

幾丁聚醣 硫酸化軟骨素 基因載體 聚乙烯亞胺 chitosan chondroitin sulfate gene carrier polyethylene imine
The purpose of this study was to design a gene vector for gene therapy. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, its low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imine (PEI) and polyethylene glycol (PEG) onto polymers can increase their solubility. This study reports a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency. Two molecular weights (Mw= 600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1.8K-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1.8K-g-CHI/DNA or CHI/DNA polyplexes. Polyethylene imine (PEI) is commonly used for gene transfer. However, the high cytotoxicity often leads to decreased transfection efficiency. Solutions to this problem have been widely discussed, one of which being the grafting of highly biocompatible polymer such as chondroitin sulfate (CS). In this study, different molecular weight (1.8K and 25K Da) of PEI was grafted onto CS (PEI1.8K-g-CS and PEI25K-g-CS) through ethyl(dimethylaminopropyl) carbodiimide (EDC)/N-Hydroxysuccinimide (NHS) reaction. This modification resulted in a non-viral gene carrier with improved biocompatibility. The transfection efficiency of BMSCs using PEI25K-g-CS/DNA polyplexes was significantly higher than PEI25K/DNA polyplexes.

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