1] Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA. [2].
Nat Med. 2013 Sep;19(9):1111-3. doi: 10.1038/nm.3261. Epub 2013 Aug 4.
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.
线粒体疾病通常由突变的线粒体 DNA (mtDNA)引起，在大多数情况下，突变型 mtDNA 与野生型 mtDNA 共存，导致 mtDNA 异质性。我们设计了转录激活样效应物核酸酶（TALENs）使其定位于线粒体并切割不同类型的致病性 mtDNA 突变。线粒体靶向 TALEN（mitoTALEN）表达导致患者来源细胞中缺失或点突变 mtDNA 的永久性减少，这增加了这些线粒体核酸酶可能对某些线粒体疾病具有治疗作用的可能性。
