Portal de Periódicos da CAPES

Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs

2013; Nature Portfolio; Volume: 19; Issue: 9 Linguagem: Inglês

10.1038/nm.3261

1546-170X

Sandra R. Bacman, Siôn L. Williams, Milena Pinto, Susana Peralta, Carlos T. Moraes,

ATP Synthase and ATPases Research

Mutations in mitochondrial DNA that inhibit the normal function of this organelle can result in disease if a sufficient percentage of mitochondria in the body's cells harbor such alterations. Using transcription activator–like effector nuclease (TALEN) technology, Carlos Moraes and his colleagues show that mutant mitochondria can be selectively targeted and eliminated, allowing for a sufficient percentage increase of normal mitochondria and thus restoration of normal respiration in a cell-based model. 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.