Manipulation of mitochondrial genes and mtDNA heteroplasmy

被引：20

作者：

Bacman, Sandra R. ^{[1
]}

Gammage, P. A. ^{[2
]}

Minczuk, M. ^{[3
]}

Moraes, Carlos T. ^{[1
]}

机构：

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

[2] CRUK Beatson Inst Canc Res, Glasgow, Lanark, Scotland

[3] Univ Cambridge, MRC Mitochondrial Biol Unit, Cambridge, England

来源：

MITOCHONDRIA, 3RD EDITION | 2020年 / 155卷

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

ZINC-FINGER-NUCLEASE; CRYSTAL-STRUCTURE; DNA HETEROPLASMY; MOUSE MODEL; SELECTIVE ELIMINATION; RESTRICTION ENZYMES; BINDING SITES; TAL EFFECTORS; VIRAL VECTORS; MUTANT MTDNA;

D O I：

10.1016/bs.mcb.2019.12.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Most patients with mitochondrial DNA (mtDNA) mutations have a mixture of mutant and wild-type mtDNA in their cells. This phenomenon, known as mtDNA heteroplasmy, provides an opportunity to develop therapies by selectively eliminating the mutant fraction. In the last decade, several enzyme-based gene editing platforms were developed to cleave specific DNA sequences. We have taken advantage of these enzymes to develop reagents to selectively eliminate mutant mtDNA. The replication of intact mitochondrial genomes normalizes mtDNA levels and consequently mitochondrial function. In this chapter, we describe the methodology used to design and express these nucleases in mammalian cells in culture and in vivo.

引用

页码：441 / 487

页数：47

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