Antisense oligonucleotides mechanisms

Cell membranes are lipophilic and designed to be barriers against large anionic molecules, although there is a natural mechanism for intercellular transport of anionic oligonucleotides. In order to enhance membrane transport, antisense oligonucleotides are frequentiy modified by covalent attachment of carrier molecules or lipophilic groups. 

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... 

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... 

Ropert, C., Malvy, C., Couvreur, P. (1993). Inhibition of the Friend retrovirus by antisense oligonucleotides encapsulated in liposomes mechanism of action. Pharm. Res., 10, 1427-1433. 

Boiziau, C., Thuong, NT. and Toulme, J.-J. (1992b) Mechanisms of the inhibition of reverse transcription by antisense oligonucleotides. Proc. Natl. Acad. Sci. USA, 89, 768-772. 

Nechers, L.M. (1989) Antisense oligonucleotides as a tool for studying cell regulation mechanism of uptake and application to the study of oncogene function. In J.S.Cohen (ed.) Oligodeoxyribonucleotides Antisense Inhibitors of Gene Expression. Macmillan Press, London. 

Dias N, Stein CA (2002) Antisense oligonucleotides basic concepts and mechanisms. Mol Cancer Ther l(5) 347-355... 

Bolziau C, Kurfist R, Cazenave C, RoigV Thoung NT Toulme JJ. Inhibition of translation initiation by antisense oligonucleotides via an RNAase independent mechanism, Nucleic Acid Res 1991 I 9 1 I 13-1 I 19. 

Burgess TL, Fisher ER Ross SL, et al. The antiproliferative effect of c-myb and c-myc antisense oligonucleotides in smooth muscle cells is caused by a non antisense mechanism. Proc Natl Acad Sci USA I 995 92(9) 405l-4055. 

Zelphati, O., Imbach, J. L., Signoret, N., Zon, G., Rayner, B., and Leserman, L. (1994). Antisense Oligonucleotides in Solution or Encapsulated in Immunoliposomes Inhibit Replication of Hiv-1 by Several Different Mechanisms. Nucleic Acids Res. 22 4307-4314. 

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