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Modification of small interfering RNAs to prevent off-target effects by the sense strand

Paper ID Volume ID Publish Year Pages File Format Full-Text
33415 44977 2013 7 PDF Available
Title
Modification of small interfering RNAs to prevent off-target effects by the sense strand
Abstract

ObjectiveThere is a broad therapeutic potential for the application of small interfering RNAs (siRNAs). However, one has to ensure that siRNAs act specifically, only targeting the expression of one gene. Off-target effects raised by the sense strand have to be eliminated.Methods and resultsWe examined a particular bidirectional siRNA molecule, able to knockdown intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor-1 (TNFR-1) by the sense or antisense strand, respectively. Transfection of human venous endothelial cells with an unmodified siRNA molecule led to equal silencing of ICAM-1 and TNFR-1. In contrast, modified siRNA was able to knockdown ICAM-1 and TNFR-1 separately, with only the antisense strand.DiscussionWe found the modified siRNAs to inhibit off-target effects originated by the sense strand. Our approach demonstrates one possibility to modify siRNAs before starting a clinical approach to eliminate off-target effects.

► The modification is easy to conduct on already validated siRNAs. ► The modification of siRNAs is a prerequisite for their clinical application. ► The modification was able to uncover, that ICAM-1 is not silenced by this siRNA. ► The modification enhances the feeding of the antisense strand into RISC.

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Modification of small interfering RNAs to prevent off-target effects by the sense strand
Publisher
Database: Elsevier - ScienceDirect
Journal: New Biotechnology - Volume 30, Issue 2, 25 January 2013, Pages 159–165
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering