Efficient Modulation of Exon Skipping via Antisense Circular RNAs  

作　　者：Shuaiwei Ren Mei Huang Raoxian Bai Lijiao Chen Jiao Yang Junyu Zhang Wenting Guo Weizhi Ji Yongchang Chen 

机构地区：[1]State Key Laboratory of Primate Biomedical Research,Institute of Primate Translational Medicine,Kunming University of Science and Technology,Kunming 650500,China [2]Yunnan Key Laboratory of Primate Biomedical Research,Kunming 650500,China

出　　处：《Research》2023年第3期485-490,共6页研究（英文）

基　　金：the National Natural Science Foundation of China(grant numbers 81930121 and 82125008);STI2030-Major projects(grant number 2021ZD0200900);the National Key Research and Development Program of China(grant numbers 2018YFA0801403 and 2018YFA0107902);the Natural Science Foundation of Yunnan Province(grant numbers 202001BC070001 and 202102AA100053)。

摘　　要：Splice-switching antisense oligonucleotides(ASOs)and engineered U7 small nuclear ribonucleoprotein(U7 Sm OPT)are the most commonly used methods for exon skipping.However,challenges remain,such as limited organ delivery and repeated dosing for ASOs and unknown risks of by-products produced by U7 Sm OPT.Here,we showed that antisense circular RNAs(AS-circRNAs)can effectively mediate exon skipping in both minigene and endogenous transcripts.We also showed a relatively higher exon skipping efficiency at the tested Dmd minigene than U7 Sm OPT.AS-circRNA specifically targets the precursor mRNA splicing without off-target effects.Moreover,AS-circRNAs with adeno-associated virus(AAV)delivery corrected the open reading frame and restored the dystrophin expression in a mouse model of Duchenne muscular dystrophy.In conclusion,we develop an alternative method for regulating RNA splicing,which might be served as a novel tool for genetic disease treatment.

关 键 词：ENDOGENOUS DYSTROPHY DUCHENNE 

分 类 号：R74[医药卫生—神经病学与精神病学]