Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs

被引：326

作者：

Bacman, Sandra R. ^{[1
]}

Williams, Sion L. ^{[1
]}

Pinto, Milena ^{[1
]}

Peralta, Susana ^{[1
]}

Moraes, Carlos T. ^{[1
,2
]}

机构：

[1] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA

[2] Univ Miami, Miller Sch Med, Dept Cell Biol, Miami, FL 33136 USA

来源：

NATURE MEDICINE | 2013年 / 19卷 / 09期

基金：

美国国家卫生研究院;

关键词：

TARGETED RESTRICTION-ENDONUCLEASE; DNA COPY NUMBER; MTDNA HETEROPLASMY; HUMAN BRAIN; MUTATION; DELETIONS; DELIVERY; MICE;

D O I：

10.1038/nm.3261

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Mitochondrial diseases are commonly caused by mutated mitochondrial DNA (mtDNA), which in most cases coexists with wild-type mtDNA, resulting in mtDNA heteroplasmy. We have engineered transcription activator-like effector nucleases (TALENs) to localize to mitochondria and cleave different classes of pathogenic mtDNA mutations. Mitochondria-targeted TALEN (mitoTALEN) expression led to permanent reductions in deletion or point-mutant mtDNA in patient-derived cells, raising the possibility that these mitochondrial nucleases can be therapeutic for some mitochondrial diseases.

引用

收藏

页码：1111 / 1113

页数：3

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