Development of techniques to prevent transmission of mitochondrial DNA disease.

 PNT schematic

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause a range of serious, debilitating and fatal diseases. This area of research aims to develop techniques to uncouple the inheritance of nuclear DNA and mtDNA, thereby reducing the risk of an affected woman transmitting mutated mtDNA to her child.  In the context of clinical treatment, this could be accomplished by transplanting the nuclear DNA from the egg of an affected woman to an enucleated egg from an unaffected donor.  In principle, nuclear DNA can be transferred either before (Spindle transfer) of after (Pronuclear transfer). 

Proof of concept studies indicate that transplantation of the nuclear genome either before or after fertilisation provides a feasible option for reducing the risk of transmitting mtDNA disease. However, the potential of either approach as future treatments will depend on whether manipulated embryos are capable of undergoing normal development to a stage where they would be capable of implanting in the uterus. Our current research efforts are therefore focussed on optimising procedures to maximise development to the blastocyst stage in vitro, and to perform a range of tests to determine whether those blastocysts are comparable to unmanipulated embryos.

This research programme is funded by the Wellcome Trust.