sisiLNA is a novel design for gene silencing molecules composed of an intact antisense strand complemented with two shorter 10-12 nucleotide long LNA-modified sense strands. The sisiLNA technology is invented by professors Jørgen Kjems and Jesper Wengel and is covered by a recently filed patent application.
This three-stranded construct, termed small internally segmented interfering LNA (sisiLNA), is highly functional with prolonged duration of action relative to unmodified siRNA. This demonstrates that an intact sense strand is not a prerequisite for RNA interference.
When using the sisiLNA design only the antisense strand can be incorporated into activated RISC thereby completely eliminating unintended off-target mRNA targeting by the sense strand.
Interestingly, the sisiLNA design supports the silencing effect of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiLNA design has a clear potential of improving the pharmacokinetic properties of siRNA for in vivo applications.
For more information see http://nar.oxfordjournals.org/cgi/reprint/gkm548v1
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