Potent and selective inhibition of gene expression by an antisense heptanucleotide View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-07

AUTHORS

Richard W. Wagner, Mark D. Matteucci, Deborah Grant, Teresa Huang, Brian C. Froehler

ABSTRACT

Factors that govern the specificity of an antisense oligonucleotide (ON) for its target RNA include accessibility of the targeted RNA to ON binding, stability of ON/RNA complexes in cells, and susceptibility of the ON/RNA complex to RNase H cleavage. ON specificity is generally proposed to be dependent on its length. To date, virtually all previous antisense experiments have used 12–25 nt-long ONs. We explored the antisense activity and specificity of short (7 and 8 nt) ONs modified with C-5 propyne pyrimidines and phosphorothioate internucleotide linkages. Gene-selective, mismatch sensitive, and RNase H-dependent inhibition was observed for a heptanucleotide ON. We demonstrated that the flanking sequences of the target RNA are a major determinant of specificity. The use of shorter ONs as antisense agents has the distinct advantage of simplified synthesis. These results may lead to a general, cost-effective solution to the development of antisense ONs as therapeutic agents. More... »

PAGES

840-844

References to SciGraph publications

Journal

TITLE

Nature Biotechnology

ISSUE

7

VOLUME

14

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt0796-840

    DOI

    http://dx.doi.org/10.1038/nbt0796-840

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001313757

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9631007


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