| | |  | | | | Record from Web of Science® | | | | | | |
| Antisense oligonucleotides: Is the glass half full or half empty? |
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| Author(s): Bennett CF |
| Source: BIOCHEMICAL PHARMACOLOGY Volume: 55 Issue: 1 Pages: 9-19 Published: JAN 1 1998 |
| Times Cited: 105 References: 123 |
| Abstract: Antisense oligonucleotides are widely used as tools to explore the pharmacological effects of inhibiting expression of a selected gene product. In addition, they are being investigated as therapeutic agents for the treatment of viral infections, cancers, and inflammatory disorders. Proof that the pharmacological effects produced by the oligonucleotides are attributable to an antisense mechanism of action requires careful experimentation. Central to this problem is the finding that oligonucleotides are capable of interacting with and modulating function of specific proteins in both a sequence-independent and -dependent manner. Despite these undesired interactions, it has been possible to demonstrate that oligonucleotides are capable of binding to a specific RNA in cultured cells, or within tissues, resulting in selective reduction of the targeted gene product and pharmacological activity. In general, these oligonucleotides were identified after a selection process in which multiple oligonucleotides targeting different regions on the RNA were evaluated for direct inhibition of targeted gene product, resulting in the identification of a potent and selective oligonucleotide. Similar to other drug receptor interactions, selection of the most potent inhibitor results in an increase in the signal-to-noise ratio, yielding increased confidence chat activity observed is the result of a desired effect of the inhibitor. With careful selection, proper controls, and careful dose-response curves it is possible to utilize antisense oligonucleotides as effective research tools and potentially as therapeutic agents. (C) 1998 Elsevier Science Inc. |
| Document Type: Editorial Material |
| Language: English |
| Reprint Address: Bennett, CF (reprint author), ISIS PHARMACEUT, 2292 FARADAY AVE, CARLSBAD, CA 92008 USA |
| Publisher: PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB |
| Subject Category: Pharmacology & Pharmacy |
| IDS Number: YJ699 |
| ISSN: 0006-2952 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |