Discovery and development of RNAi-based therapeutics: An overview

CARB 37

Muthiah Manoharan, mmanoharan@alnylam.com, Alnylam Pharmaceuticals, 300 Third St, Cambridge, MA 02142
RNA interference (RNAi) is a powerful biological process for specific silencing of mRNAs in diversified eukaryotic cells. The technique has tremendous potential for use in functional genomics, for drug discovery through in vivo target validation, and for development of novel gene-specific medicine for virtually any disease target, including the so-called ‘non-druggable' targets. A related RNA interference process involves modulation of microRNAs to control gene expression. A critical requirement for achieving safe and efficacious RNAi therapy is introduction of “drug-like” properties, such as specificity, stability, cellular delivery, and tissue biodistribution, into synthetic siRNAs to improve in vivo pharmacological properties. Our presentation will review the role of the chemist's toolbox in this emerging technology.