MitoTev-TALE: a monomeric DNA editing enzyme to reduce mutant mitochondrial DNA levels

ABSTRACT: Pathogenic mitochondrial DNA (mtDNA) mutations often co-exist with wild-type molecules (mtDNA heteroplasmy). Phenotypes manifest when the percentage of mutant mtDNA is high (70-90%). Previously, our lab showed that mitochondria-targeted transcription activator-like effector nucleases (MitoTALENs) can eliminate mutant mtDNA from heteroplasmic cells. However, mitoTALENs are dimeric and relatively large, making it difficult to package their coding genes into viral vectors, limiting their clinical application. The smaller monomeric GIY-YIG homing nuclease from T4 phage (I-TevI) provides a potential alternative. We tested whether molecular hybrids (mitoTev-TALEs) could specifically bind and cleave mtDNA of patient-derived cybrids harboring different levels of the m.8344A>G mtDNA point mutati

SUBMITTER: Claudia Pereira 

PROVIDER: S-SCDT-EMM-2017-08084 | biostudies-other |

REPOSITORIES: biostudies-other