Delivery strategies for siRNA-mediated gene silencing.
RNA interference (RNAi) represents a promising new gene silencing technology for functional genomics and a potential therapeutic strategy for a variety of genetic diseases. RNAi involves the targeted post-transcriptional degradation of messenger RNA thereby inhibiting the synthesis of the desired protein. This effectively leads to silencing of gene expression. The effectors of this process are short interfering RNA (siRNA) duplexes (approximately 21-23nt) that are key intermediaries in the specific degradation of target mRNA following incorporation into the RNA-induced silencing complex (RISC) in the cytosol. However, due to the large molecular weight and negative charge of siRNA duplexes the effective cellular uptake and intracellular delivery appear to represent a major challenge for the widespread use of RNAi in vivo. This review summarises some of the main delivery strategies that have been attempted for the transfection of siRNA to cells in vitro and in vivo.
Gilmore
Ian R
IR
Centre for Genome-based Therapeutics, The Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3XF, UK.
Fox
Stephen P
SP
Hollins
Andrew J
AJ
Akhtar
Saghir
S
D000281:Administration, Intranasal; D000818:Animals; D016503:Drug Delivery Systems; D018274:Electroporation; D020868:Gene Silencing; D006801:Humans; D008081:Liposomes; D011108:Polymers / Q000008:administration & dosage; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D008081:Liposomes; D011108:Polymers; D034741:RNA, Small Interfering