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Science 4 June 1993:
Vol. 260. no. 5113, pp. 1510 - 1513
DOI: 10.1126/science.7684856
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Articles

Science, Vol 260, Issue 5113, 1510-1513
Copyright © 1993 by American Association for the Advancement of Science

articles

Antisense gene inhibition by oligonucleotides containing C-5 propyne pyrimidines

RW Wagner, MD Matteucci, JG Lewis, AJ Gutierrez, C Moulds, and BC Froehler

Gilead Sciences, Inc., Foster City, CA 94404.

Phosphorothioate oligodeoxynucleotides containing the C-5 propyne analogs of uridine and cytidine bind RNA with high affinity and are potent antisense inhibitors of gene expression. In a cellular assay, gene-specific antisense inhibition occurred at nanomolar concentrations of oligonucleotide, was dose-dependent and exquisitely sensitive to sequence mismatches, and was correlated with the melting temperature and length of oligonucleotide. Activity was independent of RNA target site and cell type but was detectable only when the oligonucleotides were microinjected or delivered with cell-permeabilizing agents. These oligonucleotides may have important applications in therapy and in studies of gene function.


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