Antisense inhibition mechanism

Most similar to RNAi compounds in their application and chemical nature are antisense compounds one of which, Vitravene, reached the market as an FDA-approved drug in 1998 [194,195]. Antisense oligonucleotides have been studied for their ability to knock down gene expression since 1978 [196, 197]. Later studies support that the mechanism of antisense inhibition acts either through the inhibition of translation or through RNase H-dependent degradation of mRNA [198]. 

Moulds, C. et al.. Site and mechanism of antisense inhibition by C-5 propyne oligonucleotides. Biochemistry, 34,5044,1995. 

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... 

A mbros Reasonably well. The basic mechanism is translational regulation of Lin-14 mRNA. lin-4 is a small antisense RNA which accumulates towards the end of the first larval stage and binds to the 3bUTR of lin-14 mRNA, inhibiting LIN-14 translational elongation. 

The product inhibits replication of human CMV (HCMV) via an antisense mechanism. Its nucleotide sequence is complementary to a sequence in mRNA transcripts of the major immediate early region (IE2 region) of HCMV. These mRNAs code for several essential viral proteins and blocking their synthesis effectively inhibits viral replication. 

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. 

Mechanism of Action. Fomivirsen has a unique mechanism of antiviral action. This drug contains an amino acid sequence that is opposite or complimentary to the messenger RNA sequence controlling CMV replication. Because of this opposing or antisense sequence, fomivirsen inhibits several aspects of CMV replication, and also inhibits the viruses ability to adsorb to the surface of host cells. 

It was also found that SMC proliferation could be inhibited by antisense oligomers via nonantisense mechanisms (39). In this case, the presence of four contiguous guanosine residues (G-4 tract) within the oligonucleotide sequence caused a sequence-specific, but not antisense-dependent, antiproliferative effect. 

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. 

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