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Hope for live mitochondrial gene editing

Wednesday February 9th 2022

Direct, in vivo, gene editing of mitochondrial DNA may be possible, British scientists have reported.

Dr Michal Minczuk at the University of Cambridge, UK, and colleagues explained in *Nature Communications* yesterday that mitochondria play a central role in energy provision to the cell and in several key metabolic pathways.

Mitochondrial diseases are caused by mutations in DNA that lead to impaired mitochondrial energy production. They affect about 23 people in every 100,000 and can cause severe disability and premature death.

"There are currently no effective treatments for these disorders and clinical management focuses on treating complications," explain the researchers.

They carried out successful mitochondrial DNA gene editing in mice, "providing proof-of-concept" for its use in human body tissue. This process "can install the desired mitochondrial DNA mutations in adult and neonatal mice", they confirm.

"To the best of our knowledge, such a result has not been reported in the literature thus far," they write.

Dr Minczuk commented: “Our earlier approach was very promising and was the first time that anyone had been able to alter mitochondrial DNA in a live animal. But it would only work in cells with enough healthy mitochondrial DNA to copy themselves and replace the faulty ones that had been removed. It would not work in cells whose entire mitochondria had faulty DNA.”

Co-author Dr Pedro Silva-Pinheiro added: “This is the first time that anyone has been able to change DNA base pairs in mitochondria in a live animal. It shows that, in principle, we can go in and correct spelling mistakes in defective mitochondrial DNA, producing healthy mitochondria that allow the cells to function properly.”

Silva-Pinheiro, S. et al. In vivo mitochondrial base editing via adenoassociated viral delivery to mouse post-mitotic tissue. *Nature Communications* 8 February 2022 doi: 10.1038/s41467-022-28358-w

[abstract]

Tags: Genetics | Pharmaceuticals | UK News

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