The fact is that siRNAs—the double-stranded effectors of RNA interference (RNAi)—can “be developed to silence any gene; can be developed incredibly fast; can have picomolar efficacy; [and] can have an effect that lasts for weeks.”
- In the lab, they have become invaluable tools,
- enabling the easy genetic knockdown of any sequence.
- The problem with migrating to the clinic, she says, is still delivery.
Two years is a long time in the world of RNAi therapeutics. Since Science last covered the topic in 2007, the first Phase 3 human clinical trial of an siRNA drug has been prematurely terminated; new off-target effects have been identified; and the first miRNA-based therapeutic entered clinical trials. Yet much remains the same, especially the biggest challenge: delivery. As researchers struggle to overcome these obstacles, optimism persists undiminished.
Work on that front is proceeding at a rapid clip, in both academia and industry, as a handful of clinical trials attest. At the same time, new problems have cropped up, including unanticipated immunological effects and impacts on endogenous RNA processing. Others are probing the potential of the field as a whole, for instance with so-called “single-stranded” RNAi strategies.