Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs
Open accessAbstract
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.
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TALEN can be re-engineered to target and cleave mutant mitochondrial DNA in patient-derived cells, whereas mitochondrial genome-targeting CRISPR-Cas9 remains to be explored.
“And moreover, TALEN can be re-engineered to target and cleave mutant mitochondrial DNA in patient-derived cells, 21 whereas mitochondrial genometargeting CRISPR-Cas9 remains an area to be explored.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [21]
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- Authors
- Bacman, S. R., Williams, S. L., Pinto, M., Peralta, S., & Moraes, C. T.
- Affiliations
- University of Miami (US)
- Corresponding author
- Moraes, Carlos T
- Venue
- Nature Medicine
- Published
- 2013-08-04
- Volume
- 19
- Issue
- 9
- Pages
- 1111-1113
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4153471
- OpenAlex
- W2018217184
- Cited by
- 432
- References
- 28
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 25 · 2023: 47 · 2022: 32 · 2021: 36 · 2020: 36 · 2019: 37 · 2018: 40 · 2017: 22 · 2016: 37 · 2015: 34 · 2014: 31 · 2013: 4
- FWCI
- 15.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG036871)
- National Eye Institute (R01EY010804)
- National Institute of Neurological Disorders and Stroke (R01NS079965)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- mitochondrial DNA mutations, mitochondrial heteroplasmy, mitochondrial disease, TALEN, mitochondrial targeting, mitochondrial DNA deletions, point mutations, cell therapy, mitochondrial respiration
- MeSH terms
- Amino Acid Sequence, DNA, Mitochondrial, Humans, Mitochondria, Molecular Sequence Data, Mutation, Osteosarcoma, Deoxyribonucleases, Type II Site-Specific, Mitochondrial Diseases, Cell Line, Tumor, Genome, Mitochondrial
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