Effect of Nanoparticle Conjugation on Gene Silencing by RNA Interference

• Main Authors: Singh, Neetu (Contributor), Agrawal, Amit (Contributor), Leung, Anthony (Contributor), Sharp, Phillip A. (Contributor), Bhatia, Sangeeta N. (Contributor)
• Other Authors: Harvard University- (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society, 2011-08-31T17:49:28Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (Grant R01-CA124427)
National Institutes of Health (U.S.) (Grant U54-CA119349)
National Institutes of Health (U.S.) (Grant U54- CA119335)
David H. Koch Cancer Research Fund
National Institutes of Health (U.S.) (Grant R01-CA133404)
National Cancer Institute (U.S.) (Grant PO1- CA42063)
National Cancer Institute (U.S.) (Grant P30-CA14051)