UsiRNA (UNA modified siRNA) has been shown to reduce off-target events by greater than 10-fold over standard siRNA. Vaish et. al. rationalized that the reduction in off-target effects was due to a combination of increased loading of the appropriate strand into the RNA induced silencing complex (RISC) and a decrease in silencing by a microRNA-like mechanism.(1)

In addition to dramatically reduced off-target effects, UsiRNA offers potent gene silencing. (2) It was demonstrated by Marina Biotech that replacement of the two overhang bases with UNA, coupled with a position 1 modification of the antisense (guide) strand and a position 7 modification of the sense (passenger) strand with UNA greatly reduced the off-target effects and in many cases enhanced overall efficacy of the siRNA through reduced toxicity. This work was largely confirmed through the efforts of the laboratory of Jørgen Kjems at Aarhus University in Denmark along with numerous collaborators.(3) They investigated a large number of different modifications and discovered that UsiRNA performed best and stood out from the rest of the modifications as giving the most dependable reduction of off-target effects and hence overall efficacy.

Construct

Substitution at position 7 of the antisense (guide) strand is shown to reduce microRNA-like off-target effects while maintaining siRNA potency. The sense (passenger) strand has a single 5' UNA substitution. This 5' modification prevents undesired loading of the sense (passenger) strand into RISC and eliminates potential for off-target RNAi-mediated activity (IC₅₀ as low as ~10 pM). Both strands are modified with two 3' UNA modifications to increase nuclease stability. Because UNA is not RNA, UsiRNA is not covered by the current siRNA patent suite.

Pricing

Pricing includes standard processing, PAGE QC and mass spec analysis. Yields may vary due to sequence composition. To place an order for a UsiRNA, send us your siRNA sequences that currently have off-target effects. We will replace the appropriate bases with UNA.

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