Journal
NUCLEIC ACID THERAPEUTICS
Volume 22, Issue 3, Pages 205-210Publisher
MARY ANN LIEBERT INC
DOI: 10.1089/nat.2011.0334
Keywords
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Funding
- Merck & Co., Inc., within the RNA Therapeutics Department
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The immune stimulation induced by short interfering RNAs (siRNAs) has been reported to be quieted or abrogated by methoxy or fluoro modifications of the 2' position of the ribose sugar. However, variables such as the type of modification, nucleotide preference, and strand bias have not been systematically evaluated. Here, we report the results of a screen of several modified siRNAs via a human peripheral blood monocyte cytokine induction assay. Unlike corresponding modifications of guanosine, cytidine, or uridine, 2'-fluoro modification of adenosine significantly reduced cytokine induction while retaining siRNA knockdown activity. The results of this study suggest adenosine as an optimal target for modification.
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