摘要: 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 trans-generational transmission of human mitochondrial diseases caused by mutations in mtDNA.
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期刊:
CELL
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分类:
生物学
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生物物理学
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生物物理、生物化学与分子生物学
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引用:
ChinaXiv:201605.01363
(或此版本
ChinaXiv:201605.01363V1)
DOI:10.12074/201605.01363V1
CSTR:32003.36.ChinaXiv.201605.01363.V1
- 推荐引用方式:
Reddy, Pradeep,Ocampo, Alejandro,Suzuki, Keiichiro,Luo, Jinping,Sugawara, Atsushi,Okamura, Daiji,Wu, Jun,Lam, David,Esteban, Concepcion Rodriguez,Sancho-Martinez, Ignacio,Belmonte, Juan Carlos Izpisua,Bacman, Sandra R.,Williams, Sion L.,Moraes, Carlos T.,Tsunekawa, Yuji,Xiong, Xiong,Zhao, Huimin,Montserrat, Nuria,Liu, Guang-Hui,Liu, Guang-Hui,Liu, Guang-Hui,Manau, Dolors,Civico, Salva,Cardellach, Francesc,Cardellach, Francesc,O'Callaghan, Maria del Mar,Campistol, Jaime,Campistol, Josep M.,Moraes, Carlos T..(2016).Selective Elimination of Mitochondrial Mutations in the Germline by Genome Editing.CELL.[ChinaXiv:201605.01363]
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