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

Details

Serval ID
serval:BIB_C0F96924DAF9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Selective elimination of mitochondrial mutations in the germline by genome editing.
Journal
Cell
Author(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
Publication state
Published
Issued date
23/04/2015
Peer-reviewed
Oui
Volume
161
Number
3
Pages
459-469
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
14/08/2018 9:21
Last modification date
20/08/2019 15:35
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