Rationally Targeted, Conformationally Constrained, Oxetane‐Modified Oligonucleotides Demonstrate Efficient Gene‐Silencing Activity in a Cellular System
Identifieur interne : 002F64 ( Main/Exploration ); précédent : 002F63; suivant : 002F65Rationally Targeted, Conformationally Constrained, Oxetane‐Modified Oligonucleotides Demonstrate Efficient Gene‐Silencing Activity in a Cellular System
Auteurs : J B Opalinska [Pologne] ; A M Gewirtz [États-Unis]Source :
- Annals of the New York Academy of Sciences [ 0077-8923 ] ; 2005-11.
English descriptors
- Teeft :
- Antisense, Antisense oligodeoxynucleotides, Antisense oligonucleotides, Biologic activity, Cell lysates, Cellular system, Control cells, Dppz moiety, Duplex, Gene expression, Gewirtz, Hamster fibroblast cells, Hybrid duplex, Hybridization, Identical sequence, Invitrogen corporation, Large decrease, Mapping procedure, Modification, Molecule, Mrna, Mrna levels, Mrna target, Nuclease stability, Nucleic, Nucleic acid, Nucleic acids, Nucleoporation, Nucleoside, Oligonucleotides, Opalinska, Opalinska gewirtz, Oxetane, Oxetane molecules, Phosphorothioate, Protein expression, Pvdf membrane, Real time detection, Rnase, Same extent, Slot blot, Sqrm, Sqrm molecules, Thermodynamic stability, Transfected cells, York academy.
Abstract
Antisense oligodeoxynucleotides (AS ODN) have been employed as gene‐silencing agents in the laboratory and, in the clinic. The in vivo use of these molecules has been facilitated by chemical modifications to the DNA backbone which augment their nuclease stability. Attempts to further improve the efficacy of AS ODN have largely focused on 2′ alterations of the ribose sugar that make the molecules more RNA like in structure. This increases the Tm of formed DNA/RNA hybrids but simultaneously prevents binding of RNaseH which is important for ODN effectiveness. Herein, we demonstrate the use of AS ODN containing nucleosides with a novel oxetane (OXE) modification [oxetane, 1‐(1′, 3′‐O‐anhydro‐β‐D‐psicofuranosyl nucleosides)] which augments Tm, enhances nuclease stability, and is permissive of RNaseH activation. We also illustrate herein the value of rational targeting of OXE modified, and by analogy, AS ODN of any chemical modification.
Url:
DOI: 10.1196/annals.1359.007
Affiliations:
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The in vivo use of these molecules has been facilitated by chemical modifications to the DNA backbone which augment their nuclease stability. Attempts to further improve the efficacy of AS ODN have largely focused on 2′ alterations of the ribose sugar that make the molecules more RNA like in structure. This increases the Tm of formed DNA/RNA hybrids but simultaneously prevents binding of RNaseH which is important for ODN effectiveness. Herein, we demonstrate the use of AS ODN containing nucleosides with a novel oxetane (OXE) modification [oxetane, 1‐(1′, 3′‐O‐anhydro‐β‐D‐psicofuranosyl nucleosides)] which augments Tm, enhances nuclease stability, and is permissive of RNaseH activation. We also illustrate herein the value of rational targeting of OXE modified, and by analogy, AS ODN of any chemical modification.</div></front></TEI><affiliations><list><country><li>Pologne</li><li>États-Unis</li></country></list><tree><country name="Pologne"><noRegion><name sortKey="Opalinska, J B" sort="Opalinska, J B" uniqKey="Opalinska J" first="J B" last="Opalinska">J B Opalinska</name></noRegion><name sortKey="Opalinska, J B" sort="Opalinska, J B" uniqKey="Opalinska J" first="J B" last="Opalinska">J B Opalinska</name></country><country name="États-Unis"><noRegion><name sortKey="Gewirtz, A M" sort="Gewirtz, A M" uniqKey="Gewirtz A" first="A M" last="Gewirtz">A M Gewirtz</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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