Reacción a "Harmful mutations in human mitochondrial DNA corrected through gene editing"

The genetic material (DNA) in our cells is like a complex ‘instruction manual’ that defines our body's functions at the molecular level. Errors in this manual (DNA mutations) can lead to genetic diseases, which can be fatal. The development of technologies for the precise and efficient correction of these mutations is essential for the establishment of gene therapies. In the last decade, there have been major advances in the therapeutic correction of DNA mutations located in the nucleus of human cells, mainly using technologies derived from CRISPR, a platform that received the Nobel Prize in Chemistry in 2020. However, the genetic material stored in mitochondria has not been as easy to manipulate.

Based on previous developments of alternative technologies to CRISPR for precise editing of mitochondrial DNA, the authors of this study demonstrated for the first time the usefulness of these tools in organoids (three-dimensional cell cultures), which can provide essential information in preclinical studies. In addition, the authors corrected a mitochondrial DNA mutation in cells derived from patients, a strategy that has been explored in other studies but further demonstrates the therapeutic potential of mitochondrial DNA base editors. Finally, the authors explored the translational axis of their research by demonstrating for the first time the delivery of these editors in lipid nanoparticles, a promising strategy for the therapeutic transfer of these tools.

This study represents a promising proof of concept, which will be complemented by new advances and applications of mitochondrial DNA editors in lipid nanoparticles, particularly for the development of personalised gene therapies using organoids derived from patients with different mitochondrial mutations.