RNAi: a novel antisense technology and its therapeutic potential

Abstract

Antisense oligonucleotide agents induce the inhibition of target gene expression in a sequence-specific manner by exploiting the ability of oligonucleotides to bind to target RNAs via Watson-Crick hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. This technology may be used for therapeutic purposes, functional genomics, and target validation. There are three major categories of gene-silencing molecules: (1) antisense oligonucleotide derivatives that, depending on their type, recruit RNase H to cleave the target mRNA or inhibit translation by steric hindrance; (2) ribozymes and deoxyribozymes--catalytically active oligonucleotides that cause RNA cleavage; (3) small interfering double-stranded RNA molecules that induce RNA degradation through a natural gene-silencing pathway called RNA interference (RNAi). RNAi is the latest addition to the family of antisense technologies and has rapidly become the most widely used approach for gene knockdown because of its potency. In this mini-review, we introduce the RNAi effect, briefly compare it with existing antisense technologies, and discuss its therapeutic potential, focusing on recent animal studies and ongoing clinical trials. RNAi may provide new therapeutics for treating viral infections, neurodegenerative diseases, septic shock, macular degeneration, cancer, and other illnesses, although in vivo delivery of small interfering RNAs remains a significant obstacle.