Reducible poly(amido ethylenimine) directed to enhance RNA interference

Jo Hoon Jeong, L. Christensen, Lane V. Christensen, James W. Yockman, Zhiyuan Zhong, Johannes F.J. Engbersen, Won Jong Kim, Jan Feijen, Sung Wan Kim

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158 Citations (Scopus)

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.
Original languageUndefined
Pages (from-to)1912-1917
JournalBiomaterials
Volume28
Issue number10
DOIs
Publication statusPublished - 2007

Keywords

  • METIS-244639
  • IR-70184

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