Validation of a mitochondrial RNA therapeutic strategy using fibroblasts from a Leigh syndrome patient with a mutation in the mitochondrial ND3 gene.
Electron Transport Complex I
/ metabolism
Fibroblasts
/ metabolism
Genes, Mitochondrial
Genetic Therapy
/ methods
Humans
Leigh Disease
/ genetics
Liposomes
/ metabolism
Materials Science
Membrane Fusion
Microscopy, Fluorescence
Mitochondria
/ metabolism
Mitochondrial Membranes
/ metabolism
Mutation
RNA, Messenger
/ metabolism
RNA, Mitochondrial
/ therapeutic use
Transfection
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
received:
29
11
2019
accepted:
15
04
2020
entrez:
7
5
2020
pubmed:
7
5
2020
medline:
7
1
2021
Statut:
epublish
Résumé
We report on the validation of a mitochondrial gene therapeutic strategy using fibroblasts from a Leigh syndrome patient by the mitochondrial delivery of therapeutic mRNA. The treatment involves delivering normal ND3 protein-encoding mRNA as a therapeutic RNA to mitochondria of the fibroblasts from a patient with a T10158C mutation in the mtDNA coding the ND3 protein, a component of the mitochondrial respiratory chain complex I. The treatment involved the use of a liposome-based carrier (a MITO-Porter) for delivering therapeutic RNA to mitochondria via membrane fusion. The results confirmed that the mitochondrial transfection of therapeutic RNA by the MITO-Porter system resulted in a decrease in the levels of mutant RNA in mitochondria of diseased cells based on reverse transcription quantitative PCR. An evaluation of mitochondrial respiratory activity by respirometry also showed that transfection using the MITO-Porter resulted in an increase in maximal mitochondrial respiratory activity in the diseased cells.
Identifiants
pubmed: 32371897
doi: 10.1038/s41598-020-64322-8
pii: 10.1038/s41598-020-64322-8
pmc: PMC7200808
doi:
Substances chimiques
Liposomes
0
RNA, Messenger
0
RNA, Mitochondrial
0
Electron Transport Complex I
EC 7.1.1.2
MT-ND3 protein, human
EC 7.1.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
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