A Novel Technology to Prevent Mitochondrial Disorders

A Novel Technology to Prevent Mitochondrial Disorders

In an article entitled, “Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants,” published on 31st January 2013 issue of Nature (493:634–639), the lead author Daniel Paull with thirteen other associates affiliated to six research groups have announced the success of a new technique to transfer the nucleus of one human egg cell into another. This technique has the clinical potential to eliminate the inheritance of mutations in mitochondrial DNA that causes multiple diseases in the children of parents conceiving by in vitro fertilization. In this study, the researchers removed the nucleus of an unfertilized egg cell and replaced it with the nucleus of another donor’s egg cell. The team successfully performed transfer of 25 egg cells in the course of their study. A key technique in their process was the cooling of eggs to room temperature before carrying out  nuclear transfer.  Since human cells carry many copies of the mitochondria, it was important to test the ‘new’ egg cell to make sure none of the original mitochondria had passed into any fragment of  cytoplasm with the nucleus into its new home. The researchers activated the new egg cell (by a process of mild electrical stimulation) and derived several stem cell lines from the blastocyst that developed. These cell lines were grown and differentiated into many cell types such as heart cells, neurons and pancreatic beta cells. When the team examined the stem cells, they found no traces of the genome’s original mitochondria. This exchange proved stable under various scenarios that have the potential to alter the mitochondrial genotype. This was not unexpected based on previous research on mice and monkeys. But for the clinical translation of this technique, one would want to know whether the observations made with animal cells would also hold for human cells. This was a key missing piece of the puzzle that had not been revealed in any previous studies. Furthermore, the scientists plan to move toward clinical application using this technique. Next steps include the production of more mitochondrial disease-free egg cells and the generation of healthy progeny in an animal model. [summarized by Samsad Razzaque, a graduate student of Plant Biotechnology lab. DU]

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