Human mitochondrial genome surgery

Abstract

Pathogenic mitochondrial DNA (mtDNA) mutations are often in a state of heteroplasmy. The increasing mtDNA mutation load with age generally related to aggravation of symptoms and is also a one of the main sign of organism aging. Heteroplasmy shifting which can alleviate mitochondrial functionality is most perspective approach to fight mitochondrial diseases. Molecular machines to shift heteroplasmy level recognize mutant mtDNA and cut them. In general the molecular machines could be divided into two groups: mitochondria-targeted protein-only nucleases such as mitoREs, mitoZFNs, mitoTALENs, and RNA-protein systems such as mitoRGENs. The latest seem to be more flexible and offer perspective due to their reliance on Watson–Crick interactions for specific mtDNA site recognition. We discuss also some application area for the mitoRGEN systems.