Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs.
Nat Biotechnol
; 23(8): 1002-7, 2005 Aug.
Article
en En
| MEDLINE
| ID: mdl-16041363
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.
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Banco de datos:
MEDLINE
Asunto principal:
Virus de la Hepatitis B
/
Sistemas de Liberación de Medicamentos
/
ARN Interferente Pequeño
/
Hepatitis B
/
Liposomas
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos