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EnglishCystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. The 3272–26A>G and 3849+10kbC>T CFTR mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and the Acidaminococcus sp. BV3L6, AsCas12a. This genetic repair strategy is highly precise, showing very strong discrimination between the wild-type and mutant sequence and a complete absence of detectable off-targets. The efficacy of this gene correction strategy is verified in intestinal organoids and airway epithelial cells derived from CF patients carrying the 3272–26A>G or 3849+10kbC>T mutations, showing efficient repair and complete functional recovery of the CFTR channel. These results demonstrate that allele-specific genome editing with AsCas12a can correct aberrant CFTR splicing mutations, paving the way for a permanent splicing correction in genetic diseases.
Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing / Maule, G.; Casini, A.; Montagna, C.; Ramalho, A. S.; De Boeck, K.; Debyser, Z.; Carlon, M. S.; Petris, G.; Cereseto, A.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), pp. 355601-355611.
| Titolo: | Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing | |
| Autori: | Maule, G.; Casini, A.; Montagna, C.; Ramalho, A. S.; De Boeck, K.; Debyser, Z.; Carlon, M. S.; Petris, G.; Cereseto, A. | |
| Autori Unitn: | ||
| Titolo del periodico: | NATURE COMMUNICATIONS | |
| Anno di pubblicazione: | 2019 | |
| Numero e parte del fascicolo: | 1 | |
| Codice identificativo Scopus: | 2-s2.0-85070625466 | |
| Codice identificativo Pubmed: | 31391465 | |
| Codice identificativo WOS: | WOS:000479030800014 | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s41467-019-11454-9 | |
| Handle: | http://hdl.handle.net/11572/287753 | |
| Citazione: | Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing / Maule, G.; Casini, A.; Montagna, C.; Ramalho, A. S.; De Boeck, K.; Debyser, Z.; Carlon, M. S.; Petris, G.; Cereseto, A.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), pp. 355601-355611. | |
| Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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| s41467-019-11454-9.pdf | Versione editoriale (Publisher’s layout) |  | Open Access Visualizza/Apri |
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