REDUCIBLE POLY(AMIDO ETHYLENIMINE) DIRECTED TO ENHANCE RNA INTERFERENCE
SCIE
SCOPUS
- Title
- REDUCIBLE POLY(AMIDO ETHYLENIMINE) DIRECTED TO ENHANCE RNA INTERFERENCE
- Authors
- Jeong, JH; Christensen, LV; Yockman, JW; Zhong, ZY; Engbersen, JFJ; Kim, WJ; Feijen, J; Kim, SW
- Date Issued
- 2007-04
- Publisher
- ELSEVIER SCI LTD
- Abstract
- Designing synthetic macromolecular vehicles with high transfection efficiency and low cytotoxicity has been a major interest in the development of non-viral gene carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition copolymerization of triethylenetetramine and cystamine bis-acrylamide (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA). Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under physiological conditions and perform complete release of siRNA in a reductive environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA) demonstrated significantly higher suppression of VEGF than linear-polyethylenimine (PEI) (L-PEI, 25 kDa) in human prostate cancer cells (PC-3). After 5 h of transfection, substantial dissociation and intracellular distribution of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI formulation. The triggered release of siRNA by reductive degradation of poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing cytoplasmic availability of siRNA. These results suggest that the rational design of non-viral carriers should involve considerations for intracellular dissociation and trafficking of a nucleic acid drug to maximize its effect, in conjunction with formation of stable complexes under physiological conditions. (c) 2006 Elsevier Ltd. All rights reserved.
- Keywords
- poly(amido ethylenimine); siRNA; reducible polymer; non-viral gene delivery; GENE DELIVERY; SIRNA; CELLS; DNA; TRANSFECTION; COMPLEXES; POLY(ETHYLENIMINE); EXPRESSION; SYSTEM
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28904
- DOI
- 10.1016/J.BIOMATERIA
- ISSN
- 0142-9612
- Article Type
- Article
- Citation
- BIOMATERIALS, vol. 28, no. 10, page. 1912 - 1917, 2007-04
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