LNA as a modification for siRNA designs and applications

CARB 40

Jesper Wengel, jwe@chem.sdu.dk, Department of Chemistry, University of Southern Denmark, Odense M, Denmark
The use of Locked Nucleic Acid (LNA) as a constituent of RNA constructs for gene silencing applications will be discussed. LNA nucleotides improve siRNA stability, in vivo functionality, and reduce off-target effects. The novel molecular design "LNA-modified sisiRNA" for gene silencing will be discussed. The characteristics of the three-stranded sisiRNA technology include 1) a strong and long-lasting gene-silencing effect, 2) a reduced number of off-target effects, and 3) that the use of a heavily modified antisense strand is enabled. It will be discussed how this novel chemical space for siRNA designs affects activity in cell cultures and in vivo in direct comparison with various chemically modified siRNA constructs.