Format

Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1864-9. doi: 10.1073/pnas.0910603106. Epub 2010 Jan 11.

Lipid-like materials for low-dose, in vivo gene silencing.

Author information

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2010 May 25;107(21):9915.

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.

PMID:
20080679
[PubMed - indexed for MEDLINE]
PMCID:
PMC2804742
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk