Update on the development of microRNA and siRNA molecules as regulators of cell physiology.

Abstract

RNA interference (RNAi) is one of the most significant recent breakthroughs in biomedical sciences. In 2006, Drs. Fire and Mello were awarded the Nobel Price for Physiology or Medicine for their discovery of gene silencing by double-stranded RNA. Basic scientists have used RNAi as a tool to study gene regulation, signal transduction and disease mechanisms, while preclinical drug development has gained from its use in target validation and lead optimization. RNAi has also shown promise in therapeutic applications, and several synthetic RNA molecules have entered clinical trials. The family of short regulatory RNA molecules, including small interfering RNAs (siRNAs) and micro-RNAs (miRNAs), offers many possibilities for the innovative mind. When conventional small molecule inhibitors cannot be used, RNAi technology offers the possibility for sequence-specific targeting and subsequent target gene knockdown. Currently the major challenges related to RNAi -based drug development include delivery, off-target effects, activation of the immune system and RNA degradation. Although many of the expectations related to drug development have not been met thus far, these physiologically important molecules are used in several applications. This review summarizes recent patent applications concerning micro-RNA biology. Despite the somewhat unclear intellectual property right (IPR) status for RNAi, there are many possibilities for new inventions, and much remains to be learned from the physiology behind gene regulation by short RNA molecules.