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Science Translational Medicine  17 Feb 2010:
Vol. 2, Issue 19, pp. ec27
DOI: 10.1126/scitranslmed.3000960

Small interfering RNAs (siRNAs) have the unique ability to knock down the expression of virtually any gene of interest and therefore harbor great potential for the treatment of human diseases. However, major barriers to the clinical adoption of siRNA-based therapies remain, including the susceptibility of siRNA molecules to enzymatic degradation in vivo and the inability to deliver them efficiently to cells of interest. In a recent report, Love et al. describe the use of lipidoids—synthetic lipid-like materials—as carrier molecules that protect and deliver siRNAs to target tissues in an efficacious manner.

Using a combinatorial library of synthetic lipid-like materials, the researchers performed high-throughput screening and identified several lipidoid compounds capable of delivering siRNAs to the liver. Lipidoids that were formulated with a pool of siRNAs were able to knock down the expression of five hepatic genes simultaneously in mice after a single intravenous injection. The gene-silencing effects were observable after 24 hours and remained evident for several weeks after injection. Furthermore, this lipidoid-siRNA formulation efficiently silenced the expression of hepatic genes in monkeys at doses as low as 0.03 mg/kg, which is at least 30-fold lower than the amount required by current delivery systems.

The lipidoid carrier developed by Love et al. allows for the safe and efficacious delivery of siRNAs to target tissues in vivo. These findings hold great promise to facilitate the transition of siRNA-based therapies into the clinical arena, offering innovative treatments for a wide spectrum of human diseases ranging from viral infections to cancer to neurodegenerative disorders.

K. Love et al., Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl. Acad. Sci. U.S.A. 107, 1864–1869 (2010). [Full Text]

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