Embryo transfer technique could prevent maternally inherited diseases

Researchers have developed a technique that could help prevent a number of incurable genetic diseases that affect an estimated one in 6,000 people.

The technique targets diseases stemming from mutations in the DNA of energy-producing organelles, called mitochondria, which are akin to cellular batteries. Mutations in mitochondrial DNA can lead to many different human diseases, including diabetes, deafness and diseases that affect the nervous system, heart and muscles.

Mitochondria are the only organelles in animal cells that have their own genetic material — a small, circular chromosome containing 37 genes — distinct from the DNA in the nucleus. While nuclear DNA comes from both the mother and the father, mitochondrial DNA — whether healthy or mutated — is inherited only from the mother.

The new technique, reported online April 14 in Nature, transplants nuclear DNA from human embryos with faulty mitochondria into embryos with healthy cellular batteries.

“Because we can’t cure these diseases, we turned our attention to preventing them,” says Douglass Turnbull, a neurologist at Newcastle University in England and leader of the new study.

Last year (SN: 9/26/09, p. 8), researchers showed that swapping the nuclear DNA from one rhesus monkey egg to another could effectively separate the main genetic information contained in the nucleus from diseased mitochondria.

Turnbull and his team have extended that work to humans using not eggs but human embryos created during fertility treatments. The researchers used nonviable embryos that had been fertilized by two sperm or by sperm that did not carry DNA. Such embryos would not develop properly and would otherwise have been discarded.

The researchers selected the embryos about 18 hours after fertilization, before the nuclear DNA from the egg and sperm had fused. At this stage, the DNA is packaged into structures known as pronuclei. The researchers plucked the pronuclei from one embryo and transferred them to another from which the nuclear DNA had been removed. Tests showed that no more than trace amounts of mitochondrial DNA got transferred at the same time as the pronuclei, raising the possibility that the technique could be used to move nuclear DNA from the embryo of a mother carrying diseased mitochondria into another embryo with healthy batteries.

Both the egg transfer and the new embryo transfer have their strengths and weaknesses, says Shoukhrat Mitalipov, a developmental biologist at Oregon Health and Science University in Beaverton. He led the team that performed the 2009 work, producing two baby monkeys in the process.

This new transfer of DNA in embryos is technically difficult because pronuclei are large, and the difficulty of moving large packets of DNA may reduce the efficiency of the technique, Mitalipov says. On the other hand, extra embryos created during fertility treatments are often frozen for storage at precisely the stage used in this technique, so there may be a large pool of potential donor embryos that people with mitochondrial diseases could draw from. 

Although the egg technique is easier and doesn’t involve destroying an embryo, those transfers would require eggs freshly harvested from a paid donor, he says.

Turnbull agrees that much work needs to be done before either technique will be available for clinical use. “There are still questions about safety and efficiency that we still need to tackle,” he says.