In vivo RNAi: New concepts and applications of siRNA-based therapeutic agents

BIOT 190

Tariq M. Rana, Biochemistry and Molecular Pharmacology, UMASS Medical School, 364 Plantation Street, Worcester, MA 01605
Development of siRNA-based therapies faces three challenges: (1) a better understanding of RNAi mechanism in humans, (2) identification of stable and effective siRNA sequences, and (3) efficient and specific tissue-targeted delivery in vivo. We have designed and created non-toxic water soluble nanoparticles and nanotubes to deliver siRNA into cells and silence specific genes in animals. To identify stabilized siRNAs, diverse sets of chemical modifications were created in siRNAs to determine the biochemical properties required for sustained RNAi in vivo. Results showing chemically modified siRNAs combined with our nanotechnologies to silence a variety of endogenous genes involved in neurodegenerative disease, cholesterol metabolism, and in regulating HIV replication will be presented.