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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1998-7-7
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pubmed:abstractText |
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.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1087-0156
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
840-4
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9631007-Animals,
pubmed-meshheading:9631007-Base Sequence,
pubmed-meshheading:9631007-Cell Line,
pubmed-meshheading:9631007-Cercopithecus aethiops,
pubmed-meshheading:9631007-Cost-Benefit Analysis,
pubmed-meshheading:9631007-Gene Expression Regulation,
pubmed-meshheading:9631007-HeLa Cells,
pubmed-meshheading:9631007-Humans,
pubmed-meshheading:9631007-Nucleic Acid Conformation,
pubmed-meshheading:9631007-Oligonucleotides, Antisense,
pubmed-meshheading:9631007-RNA,
pubmed-meshheading:9631007-Ribonuclease H
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pubmed:year |
1996
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pubmed:articleTitle |
Potent and selective inhibition of gene expression by an antisense heptanucleotide.
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pubmed:affiliation |
Gilead Sciences, Foster City, CA 94404, USA.
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pubmed:publicationType |
Journal Article
|