Manipulation of mitochondrial genes and mtDNA heteroplasmy.
Gene therapy
Heteroplasmy
Mitochondrial diseases
mitoTALEN
mtDNA
mtZFN
Journal
Methods in cell biology
ISSN: 0091-679X
Titre abrégé: Methods Cell Biol
Pays: United States
ID NLM: 0373334
Informations de publication
Date de publication:
2020
2020
Historique:
entrez:
19
3
2020
pubmed:
19
3
2020
medline:
29
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32183972
pii: S0091-679X(19)30159-1
doi: 10.1016/bs.mcb.2019.12.004
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Transcription Activator-Like Effector Nucleases
EC 3.1.-
Zinc Finger Nucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
441-487Subventions
Organisme : Medical Research Council
ID : MC_UU_00015/4
Pays : United Kingdom
Informations de copyright
© 2020 Elsevier Inc. All rights reserved.