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N Biotechnol. 2013 Jan 25;30(2):159-65. doi: 10.1016/j.nbt.2012.10.001. Epub 2012 Nov 1.

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

Author information

1
Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Germany.

Abstract

OBJECTIVE:

There 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 RESULTS:

We 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.

DISCUSSION:

We 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.

PMID:
23124048
DOI:
10.1016/j.nbt.2012.10.001
[Indexed for MEDLINE]

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