Antiviral agents antisense oligonucleotides

A new antiviral agent, developed for treatment of CMV retinitis, can be administered by intravitreal injection. Formivirsen sodium is a phosphorothioate oligonucleotide that inhibits CMV replication through an antisense mechanism. It is formulated as a sterile and preservative-free solution and supplied in single-use vials (Vitravene ). The product is administered directly into the vitreous cavity posterior to the limbus through a 30-gauge needle. This procedure can be performed on an... 

Fomivirsen (Vitravene), an anti-CMV agent, is the first antisense oligonucleotide to be approved by the U. S. Food and Drug Administration (FDA) as an antiviral therapy. Fomivirsen is an oligonucleotide complementary to the major immediate early region 2 (IE2) of CMV mRNA. By binding to IE2 mRNA, fomivirsen prevents its translation to protein and thereby blocks viral replication. Because this mechanism of action is... 

The contraindications to and tolerance of interferon-based therapies in the treatment of HCV infection are similar to those described for patients with HBV infection. As for HBV infection, considerable efforts are being made to develop new agents to improve response rates in patients with HCV infection. Direct antiviral strategies with antisense oligonucleotides, ribozymes, and inhibitors of the viral enzymes— polymerase, helicase, and protease—are under investigation. However, it is likely that interferons will continue to serve as the foundation of therapy for HCV infections, with new agents serving as adjuncts. 

Fig. 8.5. Structure of fomivirsen, the first marketed antisense therapeutic agent. (Adapted from Field AK. Viral targets for antisense oligonucleotides a mini review. Antiviral Res 1998 37 67-81 with permission.)...

Prasad, V. et al.. Oligonucleotides tethered to a short polyguanyHc acid stretch are targeted to macrophages enhanced antiviral activity of a vesicular stomatitis virus-specific antisense oligonucleotide, Antimicrob. Agents Chemother., 43,2689,1999. 

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