Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective.
gene therapy
heteroplasmy
mitoTALEN
mitochondrial disease
mtDNA
mtZFN
Journal
Trends in molecular medicine
ISSN: 1471-499X
Titre abrégé: Trends Mol Med
Pays: England
ID NLM: 100966035
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
17
12
2019
revised:
19
02
2020
accepted:
21
02
2020
entrez:
27
6
2020
pubmed:
27
6
2020
medline:
9
7
2021
Statut:
ppublish
Résumé
Mutations of mitochondrial DNA (mtDNA) often underlie mitochondrial disease, one of the most common inherited metabolic disorders. Since the sequencing of the human mitochondrial genome and the discovery of pathogenic mutations in mtDNA more than 30 years ago, a movement towards generating methods for robust manipulation of mtDNA has ensued, although with relatively few advances and some controversy. While developments in the transformation of mammalian mtDNA have stood still for some time, recent demonstrations of programmable nuclease-based technology suggest that clinical manipulation of mtDNA heteroplasmy may be on the horizon for these largely untreatable disorders. Here we review historical and recent developments in mitochondrially targeted nuclease technology and the clinical outlook for treatment of hereditary mitochondrial disease.
Identifiants
pubmed: 32589937
pii: S1471-4914(20)30062-9
doi: 10.1016/j.molmed.2020.02.006
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
698-709Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.