Researchers have for the first time succeeded in replacing defective mitochondrial genomes with healthy ones in monkey embryos--a technique that could be used to prevent children from inheriting a variety of incurable genetic diseases caused by defective mitochondrial genes, they report online today (August 26) in Nature.

A mitochondrion
Image: Wikipedia

"The general idea of preventing mitochondrial diseases by altering egg cells has been around for quite a while now," David Samuels, a professor of molecular physiology and biophysics at Vanderbilt University School of Medicine, told The Scientist in an email. "The difficulty has been in working out how to actually carry out the procedure without harming the egg cell," added Samuels, who was not involved in the study.

Mitochondria, which generate most of the cell's energy supply, contain their own genome, distinct from the cell's nuclear DNA, which is inherited exclusively through the mother. Mutations in mitochondrial...

Shoukhrat Mitalipov and his colleagues from Oregon National Primate Research Center devised a way to replace that defective DNA by combining in vitro fertilization with cell surgery to generate functional eggs in rhesus monkeys. First, they removed the nucleus from a donor egg cell and replaced it with the nucleus—including nuclear DNA—from the mother's egg cell. They then fertilized the egg with the father's sperm, creating an oocyte which contains the parents' nuclear genes and another female's healthy mitochondrial genes.

"Mitalipov's group [was] able to find a time in the egg cell's development when the nuclear DNA and mitochondrial DNA are safely separated, so that they could pull the nuclear DNA out of the egg cell without also pulling out any detectible amount of the mitochondrial DNA," Samuels said.

After transplanting 15 manipulated embryos into nine rhesus monkeys, the scientists found that the reconstructed eggs functioned normally, supporting healthy fertilization and embryo development. Three of the nine rhesus macaques became pregnant, the first giving birth to twins by caesarean section on April 24 of this year.

"So far, we have produced four infants from this method and they are all healthy," Masahito Tachibana, an author on the study, said in a telephone press briefing. He said that the group hopes to take the approach to clinical trials in a few years. "It is important to stop transmission of these [mitochondrial] mutations," Tachibana said. Samuels pointed out, however, that the technique does nothing to help those who already have inherited pathogenic mitochondrial DNA or who already have a mitochondrial disease.

Additionally, researchers do not fully understand the implications of transferring one person's mitochondrial genes into a different nuclear background. "This study was very well done, and the data look very convincing," said M. Flint Beal, a professor of neurology and neuroscience at the Weill Medical College of Cornell University, who was not involved in the research. He added that it provides the first real possibility of preventing mitochondrial diseases. But, he cautioned, "[t]here may be unexpected interactions between the nuclear DNA and mitochondrial DNA."


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