Conjugation of siRNA with Comb-Type PEG Enhances Serum Stability and Gene Silencing Efficiency

被引：41

作者：

Gunasekaran, Karthikeyan ^{[1
]}

Nguyen, Thi H. ^{[2
]}

Maynard, Heather D. ^{[2
]}

Davis, Thomas P. ^{[3
]}

Bulmus, Volga ^{[1
,4
]}

机构：

[1] Univ New S Wales, Sch Biotechnol & Biomol Sci BABS, Sydney, NSW 2052, Australia

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Calif NanoSyst Inst, Los Angeles, CA 90095 USA

[3] Univ New S Wales, Sch Chem Sci & Engn, Australian Ctr Nanomed, Sydney, NSW 2052, Australia

[4] Izmir Inst Technol, Dept Chem Engn, TR-35430 Izmir, Turkey

来源：

MACROMOLECULAR RAPID COMMUNICATIONS | 2011年 / 32卷 / 08期

基金：

澳大利亚研究理事会;

关键词：

biological applications of polymers; PEG(meth)acrylate; polymer conjugates; reversible addition fragmentation chain transfer polymerization (RAFT); siRNA; POLYELECTROLYTE COMPLEX MICELLES; POLY(ETHYLENE GLYCOL)-SIRNA CONJUGATE; LIVING RADICAL POLYMERIZATION; VEGF SIRNA; REVERSIBLE ADDITION; DELIVERY; PEGYLATION; POLYMERS; PEPTIDE; DESIGN;

D O I：

10.1002/marc.201000804

中图分类号：

O63 [高分子化学（高聚物）];

学科分类号：

070305 ; 080501 ; 081704 ;

摘要：

A thiol-modified siRNA targeting the enhanced green fluorescence protein (eGFP) gene was conjugated with RAFT-synthesized, pyridyl disulfide-functional poly(PEG methyl ether acrylate) s (p(PEGA) s). siRNA-p(PEGA) conjugates demonstrated significantly enhanced in vitro serum stability and nuclease resistance compared to the unmodified and thiol-modified siRNA. The complexes of siRNA-p(PEGA) conjugates with a fusogenic peptide, KALA ((+)/(-) = 2) inhibited the protein expression approximately 28-fold more than the KALA complex of the unmodified siRNA. The protein inhibition caused by siRNA-p(PEGA)-KALA complexes (56 +/- 5%-58 +/- 3% of the fluorescence expressed in non-treated cells) was comparable to the effect of the unmodified siRNA-lipofectamine complex (77 +/- 7%).

引用

页码：654 / 659

页数：6

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