Antisense oligonucleotides agents

An effective therapeutic agent must also have the abiUty to reach its target sequence m vivo. BioavailabiUty requires that the antisense oligonucleotide be able to pass through the cell membrane, and that it have a low affinity for nontarget cellular compartments and, in animal systems, nontarget organs. 

Antiselective poisoning, 5 258 Antisense agents, 77 626-627 Antisense compounds, 77 13-14 Antisense mechanism, 77 627 Antisense oligonucleotides, 77 627, 628 Antiseptics, 3 605, 606... 

It is important to realize however that these antisense molecules were not specifically targeted to the endothehum. Consequently, the contribution of the endothelial cells to the effects observed is unknown. Furthermore, in these studies adequate control experiments with mismatched ohgonucleotides are essential, since polyanionic agents such as antisense oligonucleotides can exert a broad range of non-specific antisense effects due to non-specific binding to proteins [117]. 

Geiger T, Muller M, Dean NM, Fabbro D (1998) Antitumor activity of a PKC-alpha antisense oligonucleotide in combination with standard diemotherapeutic agents against various human tumors transplanted into nude mice. Anticancer Drug Des 13 35-45... 

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. 

An effective therapeutic agent must also have the ability to reach its target sequence in vivo. In order to enhance membrane transport, antisense oligonucleotides are frequently modified by covalent attachment of carrier molecules or lipophilic groups. 

ANTI-MDM2 ANTISENSE OLIGONUCLEOTIDES AS ANTITUMOR AGENTS... 

Stein, C.A. and Cheng, Y.C. (1993) Antisense oligonucleotides as therapeutic agents—Is the bullet really magical Science, 261, 1004-1012. 

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