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A Simple Alternative to Stereotactic Injection for Brain Specific Knockdown of miRNA
Published on: December 26, 2015
Adenosine modification may be preferred for reducing siRNA immune stimulation
Raymond V Fucini1, Henry J Haringsma, Patricia Deng
1Sirna Therapeutics, a wholly owned subsidiary of Merck and Co., San Francisco, California, USA.
Abstract:
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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