Development of Nucleic-Acid Carrier Platform for Gene Expression and Silencing

• Main Authors: Tseng, S-Ja, 曾士傑
• Other Authors: Tang, Shiue-Cheng
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/92370232657273242265

博士 === 國立清華大學 === 化學工程學系 === 98 === Naturally occurring extracellular matrices (ECMs) have shown great potential in clinical applications as tissue substrates to facilitate tissue repair and regeneration. Among the commercialized ECMs, porcine small intestinal submucosa (SIS) has been used in patients for wound treatment and soft tissue reconstruction. However, there have been no reports exploring the electrostatic properties of SIS as a substrate to control localized nucleic acid delivery. We have demonstrated that the negatively charged glycosaminoglycan (GAG) content in SIS was able to associate with the cationic polymer/DNA polyplexes through electrostatic adsorption and led to transfection upon cellular adhesion. However, a major challenge to the development of localized nucleic acid delivery is the design of suitable vectors with low cytotoxicity. Poly(ester urethane) (PEU) is a class of biodegradable polymer that has been applied as tissue-engineering scaffolds with minimal cytotoxicity in vitro and in vivo. We have developed a method of incorporating tertiary amines and poly(ethylene glycol) (PEG) into PEU to synthesize soluble poly(amino ester glycol urethane) (PaEGU) as a novel platform for nucleic acid delivery. PaEGU can condense DNA or siRNA into nano-scale polyplexes to enter cells through endocytosis, which can be a useful tool to work with ECMs for localized gene expression and silencing applications.