Gene and base editing as a therapeutic option for cystic fibrosis—learning from other diseases

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dc.contributor.authorMention, Karen
dc.contributor.authorSantos, Lúcia
dc.contributor.authorHarrison, Patrick T.
dc.contributor.funderCystic Fibrosis Trusten
dc.contributor.funderFundação para a Ciência e a Tecnologiaen
dc.date.accessioned2019-11-20T05:25:50Z
dc.date.available2019-11-20T05:25:50Z
dc.date.issued2019-05-21
dc.description.abstractCystic fibrosis (CF) is a monogenic autosomal recessive disorder caused by mutations in the CFTR gene. There are at least 346 disease-causing variants in the CFTR gene, but effective small-molecule therapies exist for only ~10% of them. One option to treat all mutations is CFTR cDNA-based therapy, but clinical trials to date have only been able to stabilise rather than improve lung function disease in patients. While cDNA-based therapy is already a clinical reality for a number of diseases, some animal studies have clearly established that precision genome editing can be significantly more effective than cDNA addition. These observations have led to a number of gene-editing clinical trials for a small number of such genetic disorders. To date, gene-editing strategies to correct CFTR mutations have been conducted exclusively in cell models, with no in vivo gene-editing studies yet described. Here, we highlight some of the key breakthroughs in in vivo and ex vivo gene and base editing in animal models for other diseases and discuss what might be learned from these studies in the development of editing strategies that may be applied to cystic fibrosis as a potential therapeutic approach. There are many hurdles that need to be overcome, including the in vivo delivery of editing machinery or successful engraftment of ex vivo-edited cells, as well as minimising potential off-target effects. However, a successful proof-of-concept study for gene or base editing in one or more of the available CF animal models could pave the way towards a long-term therapeutic strategy for this disease.en
dc.description.sponsorshipFCT (PD/BD/130969/2017, UID/MULTI/04046/2019); CF ( VIA049, HARRIS17G0)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid387en
dc.identifier.citationMention, K., Santos, L. and Harrison, P.T., 2019. Gene and Base Editing as a Therapeutic Option for Cystic Fibrosis—Learning from Other Diseases. Genes, 10(5), (387). DOI:10.3390/genes10050387en
dc.identifier.doi10.3390/genes10050387en
dc.identifier.endpage17en
dc.identifier.issn2073-4425
dc.identifier.issued5en
dc.identifier.journaltitleGenesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9124
dc.identifier.volume10en
dc.language.isoenen
dc.publisherMDPIen
dc.relation.urihttps://www.mdpi.com/2073-4425/10/5/387
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerlanden
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectGene editingen
dc.subjectBase editingen
dc.subjectCystic fibrosisen
dc.subjectAAVen
dc.subjectRibonucleotide particleen
dc.subjectguideRNAen
dc.subjectCRISPRen
dc.subjectCas9en
dc.titleGene and base editing as a therapeutic option for cystic fibrosis—learning from other diseasesen
dc.typeArticle (peer-reviewed)en
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