Brief intro:
- Author: Shuaiwei Ren, Mei Huang, Raoxian Bai, Lijiao Chen, Jiao Yang, Junyu Zhang, Wenting Guo, Weizhi Ji, and Yongchang Chen
- Journal: Research (Wash D C)
- Doi: https://www.doi.org/10.34133/research.0045
- Publication Date: 2023-01-19
Products/Services used in the paper
Quotation shows PackGene:MyoAAV was packaged by PackGene Biotech (Guangzhou, China).
Research Field:Exon skipping
AAV Serotype:MyoAAV
Targeted organ:muscle
Animal or cell line strain:mouse model of Duchenne muscular dystrophy.
Abstract
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.
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