Studies in mice show the potential for gene editing to address mitochondrial disease

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Defective mitochondria (the “batteries” that power our body’s cells) may be repaired using gene editing technology in the future. Scientists at the University of Cambridge have shown that it is possible to modify the mitochondrial genome of living mice, paving the way for new treatments for incurable mitochondrial disease.

our cell It contains mitochondria that provide the energy for our cells to function. Each of these mitochondria is encoded by a small amount of mitochondrial DNA. Mitochondrial DNA occupies only 0.1% of the entire human genome and is inherited only from mother to child.

Defects in our mitochondrial DNA affect how well mitochondria work, Mitochondrial diseaseA serious and often fatal condition that affects 1 in 5,000 people. The illness is incurable and almost incurable.

Each cell usually has about 1,000 copies of mitochondrial DNA, and the rate of these damages or mutations determines whether or not you have mitochondrial disease. Normally, more than 60% of the mitochondria in a cell need to be defective in order to develop the disease, and the more mitochondrial defects a person has, the more serious their disease becomes. If we can reduce the proportion of defective DNA, disease There is potential for treatment.

Cells that contain a mixture of healthy mitochondrial DNA and defective mitochondrial DNA are called “heteroplasmic.” If the cell does not contain healthy mitochondrial DNA, it is “homoplasmic”.

In 2018, a team from the MRC Mitochondrial Biology Unit at the University of Cambridge applied experimental gene therapy to mice. Target and eliminate successfully Damaged mitochondrial DNA in heterocysts allows mitochondria with healthy DNA to occupy their place.

“Our previous approach was very promising and it was the first time that anyone was able to alter the mitochondrial DNA of a living animal,” explained Dr. Michal Minczuk. “But it works only in cells that have enough healthy mitochondrial DNA to copy themselves and replace the removed defective ones. It works in cells where the entire mitochondria have defective DNA. I will not. “

Published today with their latest advances Nature Communications, Dr. Minczuk et al. Edited the mitochondrial DNA of living mice using a biological tool known as the mitochondrial-based editor. Treatment is delivered to the bloodstream of mice using a modified virus and then taken up by its cells. This tool looks for unique sequences of base pairs that are a combination of A, C, G, and T molecules that make up DNA. Then change the DNA base. In this case, change C to T. This, in principle, allows the tool to correct certain “misspellings” that cause mitochondrial malfunctions.

Currently, there is no suitable mouse model for mitochondrial DNA disease, so researchers tested the mitochondrial-based editor using healthy mice. However, it shows that it is possible to edit the mitochondrial DNA genes of living animals.

Pedro Silva Pinheiro, a postdoctoral fellow in Dr. Minchuk’s lab and the lead author of the study, said: As a rule, defective mitochondrial DNA misspellings can be corrected to produce healthy mitochondria that allow cells to function properly. “

A UK-pioneered approach known as mitochondrial replacement therapy (sometimes called “three IVFs”) can replace defective maternal mitochondria with healthy donor mitochondria. However, this technique is complex, and even standard IVF succeeds less than once every three cycles.

Dr. Minchuk added: “There is clearly a long way to go before our work leads to the treatment of mitochondrial disease, but removing the complexity of mitochondrial replacement therapy, Defective mitochondria Will be repaired by children and adults. ”

Studies suggest that mitochondrial disease can be treated with gene therapy

For more information:
Silva-Pinheiro, Metal. In vivo mitochondrial base editing via delivery of adeno-related virus to postmitotic tissues of mice, Nature Communications (2022). DOI: 10.1038 / s41467-022-28358-w

Quote: Studies in mice show the potential for gene editing to address mitochondrial disease (February 8, 2022) Obtained from editing-tackle-mitochondrial on February 8, 2022.html

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Studies in mice show the potential for gene editing to address mitochondrial disease

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