Reduced off-target effects using siLNA and sisiLNA
3’-End LNA-modification of siRNAs results in very potent siLNA constructs that are very stable in serum. Additional LNA-modifications in the sense strand reduce off target effects to approximately 10% relative to unmodified siRNAs.
The three-stranded construct termed sisiLNA (small internally segmented interfering LNA) mediates very efficient gene silencing with prolonged duration of action relative to unmodified siRNA. When using sisiLNA only the antisense strand can be incorporated into activated RISC thereby completely eliminating unintended off-target mRNA targeting by the sense strand.
See an example of Gene Silencing using siLNA and sisiLNA constructs:
|100 nM siRNA siLNA sisiLNA|
|mock 186 187 189 188 188 188 sictr|
In the reporter assay in Cos7 cells expressing GFP fused to 5’UTR of CVB-3, LNA-modified siRNA (siLNA-188), as well as sisiLNA-188 have significantly better silencing activity than unmodified siRNA-188 at concentration 100 nM (Dr. Jens Kurreck and Mariola Dutkiewicz, Freie Universität Berlin, Research in progress).
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