Technology insight: therapeutic RNA interference--how far from the neurology clinic?

Abstract

As an evolutionarily conserved cellular pathway to regulate endogenous gene expression, RNA interference (RNAi) has been implicated in diverse biological processes. Biologists now routinely exploit this cellular pathway to suppress virtually any target gene in a sequence-specific manner, including dominantly acting genes that cause incurable neurodegenerative disorders. The development of RNAi as potential therapy for such diseases has generated considerable interest, partly because of the success of early studies of therapeutic RNAi in rodent models for a range of neurodegenerative diseases. In this article, we review the progress of RNAi therapy to date, and assess the challenges ahead for the application of such therapy to neurodegenerative diseases. We discuss the various strategies that might be used to achieve this goal, outline the preclinical studies that have already been completed, and highlight the experimental questions that need to be answered before human clinical trials can begin.