siRNA Chemical Architecture

Our lab is primarily interested in how different chemical modifications and structures impact therapeutic oligonucleotide distribution, durability, function, and efficacy. For any unformulated oligonucleotide to perform in vivo it must have significant sugar and backbone modification, and to accumulate in wide array of tissue and cell types its structure and conjugation must be fine-tuned for delivery. In early work we identified a multivalent siRNA chemical architecture that delivers beautifully to both brain and eye with broad distribution and a prolonged duration of effect.  As many diseases require modulation of more than one gene for therapeutic effect, we have focused our efforts on modifying this initial branched structure with alternative chemistry and conjugate moieties to expand its application to additional extra-hepatic tissues.