FEB 14, 2022 11:08 AM PST

A Gene-Editing Technique for Mitochondrial Disorders

WRITTEN BY: Carmen Leitch

The mitochondrion is a crucial organelle, and this tiny cellular powerhouse is unique in many ways. Thought to have originated from a symbiosis event long ago, mitochondria have actually retained their own little genome, separate from the nuclear genome found in most cell types, which carries our DNA. The mitochondrial genome only makes up about 0.1 percent of the human genome. But the organelle can still produce its own mitochondrial proteins, and when mutations occur in mitochondrial DNA, diseases can arise that can be severe and even fatal. About one in 5,000 people carries an error in mitochondrial DNA. But fixing those mutations would require its own approach.

Image credit: geralt/Pixabay

There are about 1,000 copies of mitochondrial DNA in any given cell. So cells may contain mixtures of faulty and normal mitochondria. It's typically thought that if more than 60 percent of a cell's mitochondria are damaged, disease will occur that becomes more serious with an increasing proportion of problematic mitochondria. Cells with mixtures of normal and abnormal mitochondria are known as heteroplasmic, while cells with only damaged mitochondria are homoplasmic.

Scientists have targeted and successfully removed faulty mitochondrial DNA from heteroplasmic cells in a mouse model, and healthy mitochondrial DNA took its place. But the technique only worked in cells with a robust supply of normal mitochondrial DNA. Now, the researchers have made another advance.

With a tool called a base editor, which targets single nucleotide bases in a DNA sequence and changes them to another, scientists were able to edit mitochondrial DNA in a live mouse model. Although the researchers were able to switch a C to a T in the mitochondrial DNA sequence, it was done in normal mice because there is not a suitable mouse model of mitochondrial disease. The proof-of-principle work has been reported in Nature Communications.

"There's clearly a long way to go before our work could lead to a treatment for mitochondrial diseases," cautioned corresponding study author Dr. Michal Minczuk. "But it shows that there is the potential for a future treatment that removes the complexity of mitochondrial replacement therapy and would allow for defective mitochondria to be repaired in children and adults."

Sources: University of Cambridge, Nature Communications

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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