Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide.

Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Research Abstract Details 

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Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Abstract Text:

Jie Xia,Anne Noronha,Ivanka Toudjarska,Feng Li,Akin Akinc,Ravi Braich,Maria Frank-Kamenetsky,Kallanthottathil G Rajeev,Martin Egli,Muthiah Manoharan,

Recently, chemically synthesized short interfering RNA (siRNA) duplexes have been used with success for gene silencing. Chemical modification is desired for therapeutic applications to improve biostability and pharmacokinetic properties; chemical modification may also provide insight into the mechanism of silencing. siRNA duplexes containing the 2,4-difluorotoluyl ribonucleoside (rF) were synthesized to evaluate the effect of noncanonical nucleoside mimetics on RNA interference. 5'-Modification of the guide strand with rF did not alter silencing relative to unmodified control. Internal uridine to rF substitutions were well-tolerated. Thermal melting analysis showed that the base pair between rF and adenosine (A) was destabilizing relative to a uridine-adenosine pair, although it was slightly less destabilizing than other mismatches. The crystal structure of a duplex containing rFoA pairs showed local structural variations relative to a canonical RNA helix. As the fluorine atoms cannot act as hydrogen bond acceptors and are more hydrophobic than uridine, there was an absence of a well-ordered water structure around the rF residues in both grooves. siRNAs with the rF modification effectively silenced gene expression and offered improved nuclease resistance in serum; therefore, evaluation of this modification in therapeutic siRNAs is warranted.

Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Publishing Authors By Initials

J Xia,A Noronha,I Toudjarska,F Li,A Akinc,R Braich,M Frank-Kamenetsky,KG Rajeev,M Egli,M Manoharan,

For similar ribonucleotides research abstracts see: ribonucleotides research

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Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: ACS chemical biology

VOLUME: 1

Page Numbers: 176-83

Journal Abbreviation: ACS Chem. Biol.

ISSN: 1554-8937

DAY: 25

MONTH: Apr

YEAR: 2006

Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101282906

Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Keywords Mesh Terms:

KEYWORDS: Ribonucleotides

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide. Information

Substance Name: Ribonucleotides

Registry Number: 0

Grant and Affiliation Information for Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide.

AFFILIATION: Alnylam Pharmaceuticals, Inc., 300 Third Street, Cambridge, Massachusetts 02142, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM55237

ACRONYM: GM

MEDLINETA: ACS Chem Biol

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