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Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing.

Nucleic Acids Res.. 2010-07; 
Glen F. Deleavey, Jonathan K. Watts, Tommy Alain, Francis Robert, Anna Kalota, Veenu Aishwarya, Jerry Pelletier, Alan M. Gewirtz, Nahum Sonenberg, and Masad J. Damha. Department of Chemistry, McGill University, MontrÉal, QC, Canada.
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Antibody Modification and Purification Services ...subtracted. As a positive control for the assay Hek-Blue cells were incubated with various doses of purified interferon alpha 2b (GenScript, NJ, USA). RESULTS AND DISCUSSION Tuning duplex binding affinity with combinations of modifications We and others... Get A Quote

摘要

We report that combining a DNA analog (2'F-ANA) with rigid RNA analogs [2'F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents with enhanced potency. The favored conformations of these two analogs are different, and combining them in a 1-1 pattern led to reduced affinity, whereas alternating short continuous regions of individual modifications increased affinity relative to an RNA:RNA duplex. Thus, the binding affinity at key regions of the siRNA duplex could be tuned by changing the pattern of incorporation of DNA-like and RNA-like nucleotides. These heavily or fully modified duplexes are active against a range of mRNA targets. Effective patterns of modification... More

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