Effect of nanoparticle conjugation on gene silencing by RNA interference.
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.
Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, Massachusetts 02139, USA.
Neetu
N
Singh
Amit
A
Agrawal
Anthony K L
AK
Leung
Phillip A
PA
Sharp
Sangeeta N
SN
Bhatia
D004337:Drug Carriers / Q000737:chemistry; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D049410:Luciferases, Renilla / Q000172:deficiency / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry*; D045663:Quantum Dots; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics*
D004337:Drug Carriers; D034741:RNA, Small Interfering; D049410:Luciferases, Renilla