Oligodeoxynucleotides as inhibitors of gene expression: a review.
The past several years have seen an explosive growth in the application of antisense oligodeoxynucleotides as modulators of gene expression. In this review, we discuss the various classes of compounds currently receiving attention. These include unmodified oligodeoxynucleotides, methylphosphonates, phosphorothioates, and alpha-oligonucleotides. The relative advantages and disadvantages of each class with regard to parameters such as (a) duplex stability (b) nuclease resistance, and (c) effectiveness of specific gene inhibition are noted. Oligodeoxynucleotides covalently linked to intercalating and other reactive groups are also described, as are possible mechanisms of oligodeoxynucleotide action. Finally, we consider potential future directions for this field and note that it holds the promise for specific gene therapy.
Stein
C A
CA
Clinical Pharmacology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cohen
J S
JS
D000998:Antiviral Agents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; C032627:methylphosphonic acid