Systemic Delivery of Short-Interfering RNA (siRNA)

Professor Mark E. Davis
Warren and Katherine Schlinger Professor
of Chemical Engineering
California Institute of Technology

Date: Thursday, March 10, 2005
Time: 4:00 p.m.
Place: Engineering II, Room 3361

ABSTRACT

RNA interference (RNAi) is rapidly becoming the method of choice for the elucidation of gene function and the identification of drug targets. As with other oligonucleotide-based strategies, RNAi is envisioned to ultimately be useful as a human therapeutic. Gene silencing by RNAi utilizes an endogenous defense mechanism in cells that is typically involved in their protection against viruses. Unlike all previous nucleic acid therapeutics, RNAi products have the potential to elicit immune responses like those observed from viruses. The behavior of short-interfering RNA (siRNA) in culture and mice will be described. Data from mice show that naked siRNAs (if properly synthesized) do not elicit immune responses like longer double stranded RNA of viruses, but also do not penetrate into cells to any significant amounts. Thus, delivery vehicles are shown to be necessary for effective intracellular uptake and action. A non-viral delivery system will be illustrated and shown to effectively deliver functional siRNA to targets in livers and tumors of mice without eliciting any immune responses or other toxicities. These data suggest a route to human therapeutics with siRNA.