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

被引:40
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
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
收藏
页码:654 / 659
页数:6
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