Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease

Abstract

Mitochondrial DNA (mtDNA) mutations are a common cause of genetic disease with pathogenic mtDNA mutations being detected in approximately 1 in 250 live births1-3 and at least 1 in 10,000 adults in the UK affected by mtDNA disease4. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. MtDNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach to prevent the transmission of human mtDNA disease5,6. Here we show that transfer of pronuclei between abnormally fertilised human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimising the procedure we found the average level of carry-over following transfer of two pronuclei is <2.0%, with many of the embryos containing no detectable donor mtDNA. We believe that pronuclear transfer between zygotes, as well as the recently described metaphase II spindle transfer, has potential to prevent the transmission of mtDNA disease in humans.