Marina Biotech this week announced that the incorporation of a proprietary technology into an siRNA could reduce toxicity caused by microRNA-like off-target activity.
The approach is based on Marina's unlocked nucleobase analogs, which are comprised of acyclic ribonucleoside analogs in which the bond between C2' and C3' atoms is broken. The resultant change in sugar structure is designed to make the analogs flexible and reduce the binding affinity of siRNA strands.
The company said that including a single UNA moiety into the guide strand of an siRNA could significantly reduce miRNA-like cytotoxic effects compared to unmodified siRNAs.
“The ability to rescue a highly active siRNA by dramatically reducing its cytotoxic effects with a single UNA substitution emphasizes the advantages of the UNA technology,” Richard Ho, Marina's executive vice president of research and development, said in a statement.