Potent and Persistent in Vivo Anti - HBV Activity of Chemically Modified siRNAs  

Oleh:

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

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 8 (Agu. 2005), page 1002-1007.
Topik: rna; in vivo; anti-HBV; RNA

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.4 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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 incororated into a specialized liposome to form a stable nucleid acid lipid particle (SNALP) and administered by intrevenous injection into mice carrying replicating HBV. The improved efficacy of siRNA-SNALP compared to unformulated siRNA correlates with a longer half life in plasma 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 day 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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