Advances, nuances, and potential pitfalls when exploiting the therapeutic potential of RNA interference.

The discovery of RNA interference (RNAi) holds the potential to alter the paradigm of medical therapeutics. With the ability to selectively silence the function of a gene, RNAi not only provides an indispensable research tool for determining the function of a gene, but also offers potential for the development of novel therapeutics that will inhibit specific genes involved in disease. New concepts in therapeutics have been uncovered through the study of RNAi. Nuances have emerged. For instance, global RNAi pathways can be affected by somatic mutations in cancer and cellular stress, such as hypoxia. Also, viral gene therapy can have unexpected effects on endogenous short noncoding RNA pathways. Therefore, it is important to understand where RNAi therapeutics enter the processing pathways. We highlight the evolving use of RNAi as a new class of therapeutics, such as for amyloidosis, and address some of the anticipated challenges associated with its clinical application.