Selective elimination of mitochondrial mutations in the germline by genome editing.

Détails

ID Serval
serval:BIB_C0F96924DAF9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Selective elimination of mitochondrial mutations in the germline by genome editing.
Périodique
Cell
Auteur(s)
Reddy P., Ocampo A., Suzuki K., Luo J., Bacman S.R., Williams S.L., Sugawara A., Okamura D., Tsunekawa Y., Wu J., Lam D., Xiong X., Montserrat N., Esteban C.R., Liu G.H., Sancho-Martinez I., Manau D., Civico S., Cardellach F., Del Mar O'Callaghan M., Campistol J., Zhao H., Campistol J.M., Moraes C.T., Izpisua Belmonte J.C.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
23/04/2015
Peer-reviewed
Oui
Volume
161
Numéro
3
Pages
459-469
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the transgenerational transmission of human mitochondrial diseases caused by mutations in mtDNA. PAPERCLIP.
Mots-clé
Animals, Cell Fusion, DNA, Mitochondrial, Embryo, Mammalian/metabolism, Endonucleases/metabolism, Female, Gene Targeting, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Inbred NZB, Mitochondrial Diseases/genetics, Mitochondrial Diseases/prevention & control, Mutation, Oocytes/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/08/2018 9:21
Dernière modification de la notice
20/08/2019 15:35
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