Effect of Nanoparticle Conjugation on Gene Silencing by RNA Interference

被引:73
作者
Singh, Neetu [1 ]
Agrawal, Amit [1 ]
Leung, Anthony K. L. [2 ]
Sharp, Phillip A. [2 ,3 ]
Bhatia, Sangeeta N. [1 ,2 ,4 ,5 ]
机构
[1] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[2] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[3] MIT, Dept Biol, Cambridge, MA 02139 USA
[4] Brigham & Womens Hosp, Div Med, Boston, MA 02115 USA
[5] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA
关键词
IN-VIVO; SIRNA DELIVERY; INTRACELLULAR DELIVERY; TARGET RNA;
D O I
10.1021/ja102132e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
RNA interference (RNAi) is a cellular process whereby the silencing of a particular gene is mediated by short RNAs (siRNAs). Although siRNAs have great therapeutic potential, cellular delivery has been a challenge. Nanoparticle-siRNA conjugates have emerged as potential delivery vehicles; however, reports describing the effects of nanoparticle conjugation on RISC incorporation and subsequent gene silencing have been mixed. In this report, we have systematically evaluated the effect of siRNA coupling strategies using a model nanoparticle system with varying conjugation schemes. We show that the accessibility of the siRNA linked to the nanoparticle and the lability of the cross-linker are critical for efficient gene knockdown.
引用
收藏
页码:8241 / +
页数:5
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