Investigators at the Massachusetts Institute of Technology (MIT; Cambridge, MA, USA) and Alnylam Pharmaceuticals (Cambridge, MA, USA) developed a novel siRNA delivery system based on fat-like molecules called lipidoids. Complexes of lipidoid-coated siRNA particles were found to readily penetrate the lipid membrane of target tissues.
In the current study, published in the January 11, 2010, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS), siRNA-lipoid complexes containing up to five separate and specific siRNA moieties were delivered to liver cells in mice and nonhuman primates. Results showed that this formulation enabled liver gene silencing in mice at doses below 0.01 mg/kg. Furthermore, it specifically inhibited expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin were observed at doses as low as 0.03 mg/kg. According to the authors, effective gene silencing was obtained at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.
"This greatly improved efficacy allows us to dramatically decrease the dose levels, and also opens the door to formulations that can simultaneously inhibit multiple genes or pathways," said senior author Dr. Daniel G Anderson, professor of biomedical engineering at MIT.
Related Links:
Massachusetts Institute of Technology
Alnylam Pharmaceuticals
