MersV1, Istex, Corpus, bibRecord, 001551

Design, biochemical, biophysical and biological properties of cooperative antisense oligonucleotides

Identifieur interne : 001551 ( Istex/Corpus ); précédent : 001550; suivant : 001552

Design, biochemical, biophysical and biological properties of cooperative antisense oligonucleotides

Auteurs : Ekambar R. Kandimalla ; Adrienne Manning ; Christopher Lathan ; Randal A. Byrn ; Sudhir Agrawal

Source :

Nucleic Acids Research [ 0305-1048 ] ; 1995.

RBID : ISTEX:09CF4901684F7B112D5B10D84216B9C306A58F00

Abstract

Short oligonucleotides that can bind to adjacent sites on target mRNA sequences are designed and evaluated for their binding affinity and biological activity. Sequence-specific binding of short tandem oligonucleotides is compared with a full-length single oligonucleotide (21mer) that binds to the same target sequence. Two short oligonucleotides that bind without a base separation between their binding sites on the target bind cooperatively, while oligonucleotides that have a one or two base separation between the binding oligonucleotides do not. The binding affinity of the tandem oligonucleotides is improved by extending the ends of the two oligonucleotides with complementary sequences. These extended sequences form a duplex stem when both oligonucleotides bind to the target, resulting in a stable ternary complex. RNase H studies reveal that the cooperative oligonucleotides bind to the target RNA with sequence specificity. A short oligonucleotide (9mer) with one or two mismatches does not bind at the intended site, while longer oligonucleotides (21mers) with one or two mismatches still bind to the same site, as does a perfectly matched 21mer, and evoke RNase H activity. HIV-1 inhibition studies reveal an increase in activity of the cooperative oligonucleotide combinations as the length of the dimerization domain increases.

Url:

https://api.istex.fr/ark:/67375/HXZ-0KVXZ7J1-R/fulltext.pdf

DOI: 10.1093/nar/23.17.3578

Links to Exploration step

ISTEX:09CF4901684F7B112D5B10D84216B9C306A58F00

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<p>Short oligonucleotides that can bind to adjacent sites on target mRNA sequences are designed and evaluated for their binding affinity and biological activity. Sequence-specific binding of short tandem oligonucleotides is compared with a full-length single oligonucleotide (21mer) that binds to the same target sequence. Two short oligonucleotides that bind without a base separation between their binding sites on the target bind cooperatively, while oligonucleotides that have a one or two base separation between the binding oligonucleotides do not. The binding affinity of the tandem oligonucleotides is improved by extending the ends of the two oligonucleotides with complementary sequences. These extended sequences form a duplex stem when both oligonucleotides bind to the target, resulting in a stable ternary complex. RNase H studies reveal that the cooperative oligonucleotides bind to the target RNA with sequence specificity. A short oligonucleotide (9mer) with one or two mismatches does not bind at the intended site, while longer oligonucleotides (21mers) with one or two mismatches still bind to the same site, as does a perfectly matched 21mer, and evoke RNase H activity. HIV-1 inhibition studies reveal an increase in activity of the cooperative oligonucleotide combinations as the length of the dimerization domain increases.</p>

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<name type="personal"><namePart type="given">Adrienne</namePart>
<namePart type="family">Manning</namePart>
<affiliation>Hybndon, Inc., 1 Innovation Drive, Worcester, MA 01604, USA, Boston, MA 02215, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
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<name type="personal"><namePart type="given">Christopher</namePart>
<namePart type="family">Lathan</namePart>
<affiliation>The Robert Mapplethorpe Laboratory for AIDS Research, Division of Hematology/Oncology, Department of Medicine, The New England Deaconess Hospital, Harvard Medical School Boston, MA 02215, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
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<name type="personal"><namePart type="given">Randal A.</namePart>
<namePart type="family">Byrn</namePart>
<affiliation>The Robert Mapplethorpe Laboratory for AIDS Research, Division of Hematology/Oncology, Department of Medicine, The New England Deaconess Hospital, Harvard Medical School Boston, MA 02215, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
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<name type="personal"><namePart type="given">Sudhir</namePart>
<namePart type="family">Agrawal</namePart>
<affiliation>Hybndon, Inc., 1 Innovation Drive, Worcester, MA 01604, USA, Boston, MA 02215, USA</affiliation>
<affiliation>*To whom correspondence should be addressed</affiliation>
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<dateIssued encoding="w3cdtf">1995-09-11</dateIssued>
<dateCreated encoding="w3cdtf">1995-06-26</dateCreated>
<copyrightDate encoding="w3cdtf">1995</copyrightDate>
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<abstract>Short oligonucleotides that can bind to adjacent sites on target mRNA sequences are designed and evaluated for their binding affinity and biological activity. Sequence-specific binding of short tandem oligonucleotides is compared with a full-length single oligonucleotide (21mer) that binds to the same target sequence. Two short oligonucleotides that bind without a base separation between their binding sites on the target bind cooperatively, while oligonucleotides that have a one or two base separation between the binding oligonucleotides do not. The binding affinity of the tandem oligonucleotides is improved by extending the ends of the two oligonucleotides with complementary sequences. These extended sequences form a duplex stem when both oligonucleotides bind to the target, resulting in a stable ternary complex. RNase H studies reveal that the cooperative oligonucleotides bind to the target RNA with sequence specificity. A short oligonucleotide (9mer) with one or two mismatches does not bind at the intended site, while longer oligonucleotides (21mers) with one or two mismatches still bind to the same site, as does a perfectly matched 21mer, and evoke RNase H activity. HIV-1 inhibition studies reveal an increase in activity of the cooperative oligonucleotide combinations as the length of the dimerization domain increases.</abstract>
<note type="author-notes">*To whom correspondence should be addressed</note>
<relatedItem type="host"><titleInfo><title>Nucleic Acids Research</title>
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<subject><topic>CHEMISTRY</topic>
</subject>
<identifier type="ISSN">0305-1048</identifier>
<identifier type="eISSN">1362-4962</identifier>
<identifier type="PublisherID">nar</identifier>
<identifier type="PublisherID-hwp">nar</identifier>
<part><date>1995</date>
<detail type="volume"><caption>vol.</caption>
<number>23</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>17</number>
</detail>
<extent unit="pages"><start>3578</start>
<end>3584</end>
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<identifier type="DOI">10.1093/nar/23.17.3578</identifier>
<identifier type="ArticleID">23.17.3578</identifier>
<accessCondition type="use and reproduction" contentType="copyright">© 1995 Oxford University Press</accessCondition>
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<original>true</original>
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Design, biochemical, biophysical and biological properties of cooperative antisense oligonucleotides

Design, biochemical, biophysical and biological properties of cooperative antisense oligonucleotides

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