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Efficient gene transfection to liver cells by a multifunctional polylactitol-based gene transporter : 폴리락티톨 기반 간세포 표적 다기능성 유전자 전달체의 개발
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- Authors
- Advisor
- Rohidas B. Arote
- Major
- 치의학대학원 치의과학과
- Issue Date
- 2015-08
- Publisher
- 서울대학교 대학원
- Keywords
- gene therapy
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 치의과학과, 2015. 8. Rohidas B. Arote.
- Abstract
- In recent years, the introduction of non-viral gene transfer systems for treatment of inherited and acquired liver diseases has attracted a lot of attention. To mediate liver-directed gene delivery, the strategy of liver cell targeting and intracellular control of gene trafficking for designing an ideal non-viral gene delivery system are a crucial and great challenge. In order to meet this needs, a new multifunctional gene carrier, polylactitol-based gene transporter (PLT) was prepared by crosslinking low molecular weight polyethylenimine (LMW PEI) with lactitol diacrylate (LDA) composed of D-galactose and D-sorbitol provides synergistic effects to increase cellular uptake, to get liver cell targeting, and to have rapid release of gene from endosome, because hyperosmotic property of polysorbitol part selectively stimulates caveolae-mediated endocytosis, polygalactose part provides liver cell targeting ability and PEI part assists rapid endosomal escape of gene due to its proton sponge effect. With these unique multifunctions, PLT/DNA nanocomplexes showed low cytotoxicity, high transfection efficiency, liver cell targeting in vitro and in vivo, and selective transition of cellular uptake pathway into the caveolae-mediated endocytosis avoiding lysosomal degradation. Taken together, PLT was confirmed as a safe and efficient vector, which will highlight a potential candidate for targeted gene therapy in the hepatic diseases.
- Language
- English
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