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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Chemistry and Biochemistry of 2, 5-Oligoadenylate-Based Antisense Strategy

Author(s): Steven A. Adah, Suzanne F. Bayly, Hagen Cramer, Robert H. Silverman and Paul F. Torrence

Volume 8 , Issue 10 , 2001

Page: [1189 - 1212] Pages: 24

DOI: 10.2174/0929867013372445

Price: $65

Abstract

This review describes the application of a natural defense mechanism to develop effective agents for The post-transcriptional control of gene expression. 2-5A is a unique 2,5-phosphodiester bond linked oligoadenylate, (pp)p5A2(p5A)n , that is elaborated in virus-infected interferon-treated cells. The 2-5A System is an RNA degradation pathway that is an important mechanistic component of interferons action against certain viruses. It may also play a role in the anticellular effects of interferon and in general RNA decay. A major player in the 2-5A-system is the latent and constitutive 2-5A-dependent ribonuclease (RNase L) which upon activation by 2-5A, degrades RNA. This RNase L enzyme can be recruited for antisense therapeutics by linking it to an appropriate oligonucleotide targeted to a chosen RNA. Syntheses of 2-5A, its analogues, 2-5A-antisense, and its modifications are detailed herein. Applications of 2-5A-antisense to particular targets such as HIV, PKR, chronic myelogenous leukemia, telomerase, and respiratory syncytical Virus is described.

Keywords: Oligoadenylate-Based Antisense, Ribonucleases, Apoptosis, 2-5A-ANTI-SENSE(2-5A-AS), Syncytial Virus, Condensation, Coupling agents


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