Lipid-like materials for low-dose, in vivo gene silencing
Name
Love-2010-Lipid-like materials.pdf
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1.19 MB
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Author(s)
Mahon, Kerry P.
Levins, Christopher G.
Whitehead, Kathryn Ann
Querbes, William
Dorkin, Joseph Robert
Qin, June
Cantley, William
Qin, Liu Liang
Racie, Timothy
Frank-Kamenetsky, Maria
Date Issued
February 2010
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Love, Kevin T. et al. “Lipid-like materials for low-dose, in vivo gene silencing.” Proceedings of the National Academy of Sciences 107.5 (2010): 1864 -1869. Copyright ©2010 by the National Academy of Sciences
Version
Final published version
Abstract
Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit 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 was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.0910603106
