Concocting a knock-out punch for HIV-1: investigators probe RNA interference as a possible therapeutic strategy against HIV-1 infection.(Hot Papers)

Since the technique hit lab benches across the world, researchers have assessed the specificity and power of gene silencing through RNA interference. RNAi has found use both as a research tool and as a potential therapeutic agent. In RNAi, an enzyme called Dicer processes long, double-stranded RNA (dsRNA) transcripts into smaller (21--25 nucleotide) dsRNAs, which target homologous messenger RNAs for degradation.

Researchers noted the phenomenon in plants more than a decade ago, and more recently it was rediscovered and refined in nematodes. In 2001, Tom Tuschl's laboratory at Rockefeller University published evidence in mammals that RNAi, mediated by short interfering RNAs (siRNAs) roughly 21 nucleotides in length, could be used to knock down gene expression. (1) Within a year, a handful of laboratories used this tool to target cellular and viral proteins necessary for human HIV-1 infection. Some of these studies have since become Hot Papers.

"All three papers basically demonstrate, to varying degrees, that it might be possible to use these small RNAs to inhibit HIV replication ... in the future, in a patient," says Phillip Sharp at Massachusetts Institute of Technology.

Though a simple plan, complications arose quickly. HIV, a particularly slippery fish, evolves resistance to most known treatments. Further, questions remain about what aspects of the HIV …