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Nat Biotechnol. 2005 Aug;23(8):1002-7. Epub 2005 Jul 24.

Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs.

Author information

1
Sirna Therapeutics, Inc., 2950 Wilderness Place, Boulder, Colorado 80301, USA. morrisseyd@sirna.com

Abstract

The efficacy of lipid-encapsulated, chemically modified short interfering RNA (siRNA) targeted to hepatitis B virus (HBV) was examined in an in vivo mouse model of HBV replication. Stabilized siRNA targeted to the HBV RNA was incorporated into a specialized liposome to form a stable nucleic-acid-lipid particle (SNALP) and administered by intravenous injection into mice carrying replicating HBV. The improved efficacy of siRNA-SNALP compared to unformulated siRNA correlates with a longer half-life in plasma and liver. Three daily intravenous injections of 3 mg/kg/day reduced serum HBV DNA >1.0 log(10). The reduction in HBV DNA was specific, dose-dependent and lasted for up to 7 d after dosing. Furthermore, reductions were seen in serum HBV DNA for up to 6 weeks with weekly dosing. The advances demonstrated here, including persistence of in vivo activity, use of lower doses and reduced dosing frequency are important steps in making siRNA a clinically viable therapeutic approach.

PMID:
16041363
DOI:
10.1038/nbt1122
[Indexed for MEDLINE]
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