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dc.contributor.authorSilva-Pinheiro, Pedro
dc.contributor.authorNash, Pavel A
dc.contributor.authorVan Haute, Lindsey
dc.contributor.authorMutti, Christian D
dc.contributor.authorTurner, Keira
dc.contributor.authorMinczuk, Michal
dc.date.accessioned2022-02-09T13:22:14Z
dc.date.available2022-02-09T13:22:14Z
dc.date.issued2022-02-08
dc.date.submitted2021-09-14
dc.identifier.issn2041-1723
dc.identifier.others41467-022-28358-w
dc.identifier.other28358
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333784
dc.description.abstractMitochondria host key metabolic processes vital for cellular energy provision and are central to cell fate decisions. They are subjected to unique genetic control by both nuclear DNA and their own multi-copy genome - mitochondrial DNA (mtDNA). Mutations in mtDNA often lead to clinically heterogeneous, maternally inherited diseases that display different organ-specific presentation at any stage of life. For a long time, genetic manipulation of mammalian mtDNA has posed a major challenge, impeding our ability to understand the basic mitochondrial biology and mechanisms underpinning mitochondrial disease. However, an important new tool for mtDNA mutagenesis has emerged recently, namely double-stranded DNA deaminase (DddA)-derived cytosine base editor (DdCBE). Here, we test this emerging tool for in vivo use, by delivering DdCBEs into mouse heart using adeno-associated virus (AAV) vectors and show that it can install desired mtDNA edits in adult and neonatal mice. This work provides proof-of-concept for use of DdCBEs to mutagenize mtDNA in vivo in post-mitotic tissues and provides crucial insights into potential translation to human somatic gene correction therapies to treat primary mitochondrial disease phenotypes.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/80/642/333
dc.subject/631/208/726/2129
dc.subject/631/208/726
dc.subject/45
dc.subject/45/23
dc.subject/45/70
dc.subject/42
dc.subject/42/44
dc.subjectarticle
dc.titleIn vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue.
dc.typeArticle
dc.date.updated2022-02-09T13:22:13Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.81201
dcterms.dateAccepted2022-01-21
rioxxterms.versionofrecord10.1038/s41467-022-28358-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSilva-Pinheiro, Pedro [0000-0002-0872-5749]
dc.contributor.orcidVan Haute, Lindsey [0000-0001-7809-1473]
dc.contributor.orcidMutti, Christian D [0000-0001-5091-5055]
dc.contributor.orcidTurner, Keira [0000-0001-9586-9523]
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.identifier.eissn2041-1723
pubs.funder-project-idMedical Research Council (MC_UU_00015/4)
cam.issuedOnline2022-02-08


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