Does RNA interference have a future as a treatment for HIV-1 induced disease?

Abstract

RNA interference has recently emerged as an effective way to block the expression of specific messenger RNAs in eukaryotic cells. Using this approach, it has proven possible to block the replication of HIV-1 in cultured cells using small interfering RNAs targeted to viral sequences or to host messenger RNAs that encode factors critical for virus replication, such as the CCR-5 coreceptor. Unfortunately, the high sequence specificity of RNA interference, combined with the known tendency of HIV-1 to rapidly generate sequence variability, means that HIV-1 variants resistant to individual small interfering RNAs targeted to the viral genome arise rapidly. However, this problem may be circumvented by simultaneously targeting several essential HIV-1 sequences using RNA interference, or by targeting host genes that are essential for virus replication. Thus, RNA interference-based approaches have the potential to prove useful as novel treatments for HIV-1 induced disease, although the problem of how to efficiently deliver small interfering RNA expression vectors, or the small interfering RNAs themselves, to cells susceptible to HIV-1 infection in vivo, remains to be resolved.