Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs
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TLDR
E engineered transcription activator-like effector nucleases (TALENs) to localize to mitochondria and cleave different classes of pathogenic mtDNA mutations 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.Abstract:
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 diseasesread more
Citations
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Expert consensus document: Mitochondrial function as a therapeutic target in heart failure
David Brown,Justin B. Perry,Mitchell E. Allen,Hani N. Sabbah,Hani N. Sabbah,Brian L. Stauffer,Saame Raza Shaikh,John G.F. Cleland,Wilson S. Colucci,Javed Butler,Adriaan A. Voors,Stefan D. Anker,Bertram Pitt,Bertram Pitt,Burkert Pieske,Gerasimos Filippatos,Stephen J. Greene,Mihai Gheorghiade +17 more
TL;DR: In this article, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.
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A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing.
Beverly Mok,Beverly Mok,Beverly Mok,Marcos H. de Moraes,Jun Zeng,Dustin E Bosch,Anna V. Kotrys,Anna V. Kotrys,Anna V. Kotrys,Aditya Raguram,Aditya Raguram,Aditya Raguram,FoSheng Hsu,Matthew C. Radey,S. Brook Peterson,Vamsi K. Mootha,Vamsi K. Mootha,Joseph D. Mougous,David R. Liu,David R. Liu,David R. Liu +20 more
TL;DR: An interbacterial toxin that catalyses the deamination of cytidines within double-stranded DNA forms part of a CRISPR-free, RNA-free base editing system that enables manipulation of human mitochondrial DNA.
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The emerging and uncultivated potential of CRISPR technology in plant science.
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Mutations causing mitochondrial disease: What is new and what challenges remain?
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Selective elimination of mitochondrial mutations in the germline by genome editing
Pradeep Reddy,Alejandro Ocampo,Keiichiro Suzuki,Jinping Luo,Sandra R. Bacman,Sion L. Williams,Atsushi Sugawara,Daiji Okamura,Yuji Tsunekawa,Jun Wu,David Lam,Xiong Xiong,Nuria Montserrat,Concepcion Rodriguez Esteban,Guang-Hui Liu,Ignacio Sancho-Martinez,Dolors Manau,Salva Civico,Francesc Cardellach,Maria del Mar O’Callaghan,Jaime Campistol,Huimin Zhao,Josep M. Campistol,Carlos T. Moraes,Juan Carlos Izpisua Belmonte +24 more
TL;DR: This work successfully reduced human mutated mtDNA levels responsible for Leber's hereditary optic neuropathy, and neurogenic muscle weakness, ataxia, and retinitis pigmentosa, in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs).
References
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Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation
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Genetic engineering of human pluripotent cells using TALE nucleases
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TL;DR: In this article, the authors used transcription activator-like effector nucleases (TALENs) for site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases.
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Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age.
Marisol Corral-Debrinski,Terzah M. Horton,Marie T. Lott,John M. Shoffner,M F Beal,Douglas C. Wallace +5 more
TL;DR: Changes in the accumulation of the common 4977 nucleotide pair (np) deletion in the cortex, putamen and cerebellum suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing.
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Mitochondrial disorders as windows into an ancient organelle
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