Realizing the Promise of RNAi

Abstract

The convergence of the discovery of RNA interference (RNAi) with the completion of the human genome sequencing program has revolutionized our methods of analyzing gene function in mammalian cells.1,2 The task of studying gene function can be relatively easily accomplished by the use of small interfering RNAs (siRNAs) for targeted inhibition of gene expression. Furthermore, use of RNAi library screens to identify specified phenotypes can be applied to drug target development.3 As such, a recent publication in Science by Brass et al.4 has stimulated a great deal of interest in the AIDS research community. This group, led by Stephen Elledge and Judith Lieberman, published an exciting application of RNAi that used an siRNA library screen to identify cellular factors required for HIV entry, replication, and infectious virus production. A handful of essential cellular host factors had previously been determined by other techniques, but this latest screen revealed more than 250 new cellular proteins required for HIV-1 to complete its replication cycle. The team termed these genes host dependency factors (HDFs). It is exciting to speculate that small-molecule drugs may be developed for some of these HDF targets in the next few years and that there may even be existing drugs that inhibit some of these HDFs that can now be developed for treating HIV-1 infection.