Manipulation of mitochondrial genes and mtDNA heteroplasmy.

TitleManipulation of mitochondrial genes and mtDNA heteroplasmy.
Publication TypeJournal Article
Year of Publication2020
AuthorsBacman, SR, Gammage, PA, Minczuk, M, Moraes, CT
JournalMethods Cell Biol
Date Published2020

Most patients with mitochondrial DNA (mtDNA) mutations have a mixture of mutant and wild-type mtDNA in their cells. This phenomenon, known as mtDNA heteroplasmy, provides an opportunity to develop therapies by selectively eliminating the mutant fraction. In the last decade, several enzyme-based gene editing platforms were developed to cleave specific DNA sequences. We have taken advantage of these enzymes to develop reagents to selectively eliminate mutant mtDNA. The replication of intact mitochondrial genomes normalizes mtDNA levels and consequently mitochondrial function. In this chapter, we describe the methodology used to design and express these nucleases in mammalian cells in culture and in vivo.

Alternate JournalMethods Cell Biol.
Citation Key10.1016/bs.mcb.2019.12.004
PubMed ID32183972