| Autor: |
Morrissey, David V, Lockridge, Jennifer A, Shaw, Lucinda, Blanchard, Karin, Jensen, Kristi, Breen, Wendy, Hartsough, Kimberly, Machemer, Lynn, Radka, Susan, Jadhav, Vasant, Vaish, Narendra, Zinnen, Shawn, Vargeese, Chandra, Bowman, Keith, Shaffer, Chris S, Jeffs, Lloyd B, Judge, Adam, MacLachlan, Ian, Polisky, Barry |
| Předmět: |
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| Zdroj: |
Nature Biotechnology; Aug2005, Vol. 23 Issue 8, p1002-1007, 6p |
| Abstrakt: |
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 log10. 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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