RNAi Therapeutics Institute
The discovery of RNA interference (RNAi) a decade ago revolutionized the scientific community’s understanding of how gene function is coordinated in cells. All plants and animals possess the machinery to effect RNA interference triggered by exogenously delivered or genetically expressed small RNAs. A number of novel strategies for using the RNAi mechanism to silence the action of individual genes were developed here at UMass Medical School (UMMS).
These discoveries offer the promise of new therapeutic approaches to diseases such as cancer, diabetes, degenerative diseases of the eye and central nervous system – including Alzheimer’s disease, Huntington’s disease, and ALS (Lou Gehrig Disease), as well as for acute and chronic viral infections such as hepatitis C virus and HIV/AIDS.
RNAi technology can be used in two complementary ways toward creating new human therapies.
- RNAi can be used as a research tool to elucidate new targets against which small molecule drugs can be identified and developed. In this way, RNAi is used to speed and focus the development of traditional drugs. The RNAi Institute will procure and be a repository for full genome-covering, short-hairpin RNA (shRNA) and small interfering RNA (siRNA) libraries that can be used in screening. The RNAi Reagents Core will prepare libraries in retroviral and lentiviral vectors applicable to most cell types. The libraries then can be applied to diverse systems in target discovery programs.
- RNAi itself can be used to reduce the hyperactivity of harmful genes. In this application, RNAi is the therapy. Most of the fundamental advances in the use of RNAi as a therapy were discovered at UMMS; the discovery of so-called ‘small interfering RNA’s’-pieces of RNA short enough to act as drugs-and the invention of shRNAs which allow RNAi to be delivered by gene therapy methods. The discovery of microRNAs which regulate gene expression in many disease states, provide new targets for RNAi therapeutics. Recently, UMMS scientists have discovered exciting new ways of prolonging the lifetime of RNAi in blood and in tissues, thereby extending the time and extent of gene silencing. These discoveries must now be translated into novel therapies for human diseases.