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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAAS
2023
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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. |
format | Online Article Text |
id | pubmed-10076032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AAAS |
record_format | MEDLINE/PubMed |
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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