Genome editing for the repair of mitochondrial mutations

Published Date
Ozge Ozkaya

A new study shows that genome editing technology could be used to prevent women from passing mitochondrial disease on to their children. 

In a recent article published in the scientific journal Cell, researchers report the first successful attempt to eliminate mutated mitochondria from the mouse egg using genome editing.

Scientists have used DNA cutting enzymes called restriction enzymes to specifically target the mutated mitochondria while sparing the healthy type.

Mitochondria are the ‘energy factories’ of cells. They have their own DNA, inherited from the mother. Each cell in the body has between 1,000 and 100,000 copies of mitochondrial DNA. Most people affected by mitochondrial disease have a mixture of mutated and healthy mitochondria in their cells. The clinical symptoms of mitochondrial disease usually arise when the ratio of mutated versus healthy mitochondria exceed 60-95%. The new genome editing technique uses restriction enzymes to target and eliminate the mutated mitochondria only, shifting the balance towards a healthy genetic state.

The researchers have first used mouse eggs carrying two different types of mitochondria and have successfully eliminated one or the other type. They then fertilised the eggs by IVF and transplanted them back in the mother’s womb. The mice gave birth to pups carrying only the non-targeted type of mitochondria.  The offspring displayed normal behaviour, development and fertility. In fact they gave birth to a second generation themselves carrying only the non-targeted type of mitochondria. This demonstrates that this technique has the potential to completely wipe out mitochondrial disease in a family.

The researchers then successfully attempted to correct a known disease causing human mitochondrial mutation using this technique. They used mouse eggs containing mutated DNA from human cells. The next step is to evaluate the safety and efficacy of the method in eggs from patients with mitochondrial diseases.

Prof Juan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies and senior author of the publication said:

This technique is based on a single injection of mRNA into a mother’s oocytes or early embryos and therefore could be easily implemented in IVF clinics throughout the world.

Dr Marita Pohlschmidt, Director of Research at Muscular Dystrophy UK said:

We welcome this exciting new technique, which could benefit thousands of women worldwide who risk passing on mitochondrial disease to their children. There are no effective ways to treat people with these devastating and unpredictable conditions, and currently, our best option is to prevent their inheritance. This approach of selectively eliminating mutated mitochondria in an egg or embryo is still at an early stage. However, the results seen in mice are promising. Initial evidence suggests that the technique may also be used for mutated human mitochondrial DNA. It does not require egg donation, and could eventually be an important alternative to mitochondrial donation IVF. We are keen to see results of further research into the technique’s safety and efficacy.

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