Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease.
Mutations in mitochondrial DNA (mtDNA) are a common cause of genetic disease. Pathogenic mutations in mtDNA are detected in approximately 1 in 250 live births and at least 1 in 10,000 adults in the UK are affected by mtDNA disease. Treatment options for patients with mtDNA disease are extremely limited and are predominantly supportive in nature. Mitochondrial DNA is transmitted maternally and it has been proposed that nuclear transfer techniques may be an approach for the prevention of transmission of human mtDNA disease. Here we show that transfer of pronuclei between abnormally fertilized human zygotes results in minimal carry-over of donor zygote mtDNA and is compatible with onward development to the blastocyst stage in vitro. By optimizing the procedure we found the average level of carry-over after transfer of two pronuclei is less than 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 the potential to prevent the transmission of mtDNA disease in humans.
Craven
Lyndsey
L
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle upon Tyne NE2 4HH, UK.
Tuppen
Helen A
HA
Greggains
Gareth D
GD
Harbottle
Stephen J
SJ
Murphy
Julie L
JL
Cree
Lynsey M
LM
Murdoch
Alison P
AP
Chinnery
Patrick F
PF
Taylor
Robert W
RW
Lightowlers
Robert N
RN
Herbert
Mary
M
Turnbull
Douglass M
DM
D001757:Blastomeres / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics*; D004622:Embryo, Mammalian / Q000737:chemistry / Q000166:cytology; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000517:prevention & control*; D053652:Nuclear Transfer Techniques; D015053:Zygote / Q000737:chemistry / Q000166:cytology
D004272:DNA, Mitochondrial
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