The sense strand pre-cleaved RNA duplex mediates an efficient RNA interference with less off-target and immune response effects |
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Authors: | Xiaozhao Lu Guodong Yang Jie Zhang Haiyan Fu Liang Jin Mengying Wei Li Wang Zifan Lu |
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Institution: | (1) Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, No. 17 Changlexi Road, 710032 Xi’an, People’s Republic of China; |
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Abstract: | RNA interference is an appealing and promising therapeutic approach in cancer and other diseases. Designing novel strategies
aiming to increase the efficiency, duration, and reduce the off-target silencing by sense strand is of great significance
for its future application clinically. Here, we report that RNA duplex with the sense strand pre-cleaved at the base between
base 10 and 11 relative to the 5′ end of the antisense strand induced a target-specific RNA silencing effectively. Furthermore,
different from the canonical RNA duplex, this novel RNA duplex rarely inhibits the luciferase activity in the reporter, bearing
the target sequence corresponding to the sense strand, suggesting a less off-target effects of this novel strategy. Furthermore,
the immune response of the novel RNA duplex induced a much milder immune response as seen from the NFkappaB activity. In addition,
our newly designed RNA duplex should be easier for preservation than the asymmetric RNA duplex. Our results establish a novel
method to design a new class of RNA duplex for improved RNA interference. |
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