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Efficient Modulation of Exon Skipping via Antisense Circular RNAs

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...

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Autores principales: Ren, Shuaiwei, Huang, Mei, Bai, Raoxian, Chen, Lijiao, Yang, Jiao, Zhang, Junyu, Guo, Wenting, Ji, Weizhi, Chen, Yongchang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAAS 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076032/
https://www.ncbi.nlm.nih.gov/pubmed/37040525
http://dx.doi.org/10.34133/research.0045
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author Ren, Shuaiwei
Huang, Mei
Bai, Raoxian
Chen, Lijiao
Yang, Jiao
Zhang, Junyu
Guo, Wenting
Ji, Weizhi
Chen, Yongchang
author_facet Ren, Shuaiwei
Huang, Mei
Bai, Raoxian
Chen, Lijiao
Yang, Jiao
Zhang, Junyu
Guo, Wenting
Ji, Weizhi
Chen, Yongchang
author_sort Ren, Shuaiwei
collection PubMed
description 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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spelling pubmed-100760322023-04-06 Efficient Modulation of Exon Skipping via Antisense Circular RNAs Ren, Shuaiwei Huang, Mei Bai, Raoxian Chen, Lijiao Yang, Jiao Zhang, Junyu Guo, Wenting Ji, Weizhi Chen, Yongchang Research (Wash D C) Research Article 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. AAAS 2023-01-19 2023 /pmc/articles/PMC10076032/ /pubmed/37040525 http://dx.doi.org/10.34133/research.0045 Text en Copyright © 2023 Shuaiwei Ren et al. https://creativecommons.org/licenses/by/4.0/Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ren, Shuaiwei
Huang, Mei
Bai, Raoxian
Chen, Lijiao
Yang, Jiao
Zhang, Junyu
Guo, Wenting
Ji, Weizhi
Chen, Yongchang
Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title_full Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title_fullStr Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title_full_unstemmed Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title_short Efficient Modulation of Exon Skipping via Antisense Circular RNAs
title_sort efficient modulation of exon skipping via antisense circular rnas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076032/
https://www.ncbi.nlm.nih.gov/pubmed/37040525
http://dx.doi.org/10.34133/research.0045
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