Scientists at Oregon Health & Science University have received significant philanthropic support to advance a first-of-its-kind method to turn an individual's skin cell into an egg, with the potential to produce viable embryos.
The technique, initially demonstrated in mice, could eventually provide a new avenue for child-bearing among couples unable to produce viable eggs of their own.
Even though the proof of concept in mice shows promise, significant challenges remain to be resolved before the technique could be ready for clinical trials under strict ethical and scientific oversight. Even then, Congress currently precludes the Food and Drug Administration from providing oversight for clinical trials involving genetic modification of human embryos.
"It will take probably a decade before we can say we're ready," said Shoukhrat Mitalipov, Ph.D., director of the OHSU Center for Embryonic Cell and Gene Therapy. "The science behind it is complex, but we think we're on the right path."
This type of research is not funded by the National Institutes of Health, so it depends on philanthropic support. For this project, Open Philanthropy awarded $4 million over three years through the OHSU Foundation.
Paula Amato, M.D., professor of obstetrics and gynecology in the OHSU School of Medicine, sees the potential for an enormous benefit to families struggling to have children if the technique proves successful.
"Age-related decline in fertility remains an intractable problem in our field, especially as women are delaying childbearing," said Amato, who is the principal investigator for the grant award.
The technique holds promise for helping families to have genetically related children, a cohort that includes women unable to produce viable eggs because of age or other causes, including previous treatment for cancer. It also raises the possibility of men in same-sex relationships having children genetically related to both partners.
"The skin cell can come from somebody who doesn't have any eggs themselves," Amato said. "The biggest implication is for female, age-related infertility. It can also come from women with premature ovarian insufficiency due to cancer treatment or genetic conditions, or from men who would be able to produce a genetically related child with a male partner."
Advancing medical research
The award from Open Philanthropy will enable OHSU researchers to develop the technique in early human embryos using eggs and sperm from research donors. As with other groundbreaking research at OHSU — including a gene-editing discovery that generated worldwide attention in 2017 — none of the early embryos will be allowed to develop past the early blastocyst stage.
Researchers will build on a study in mice published this January in the journal Communications Biology.
The study demonstrated that it is possible to produce normal eggs by transplanting skin-cell nuclei into donor eggs from which the nuclei have been removed. Known as somatic cell nuclear transfer, the technique was famously used in 1997 to clone a sheep in Scotland named Dolly. In contrast to a direct clone of one parent, the mouse study published earlier this year required OHSU scientists to cut the donor DNA in half and then fertilize the resulting egg with sperm to generate a viable embryo with chromosomes from both parents.
The process involves implanting the skin cell nuclei into a donor egg, and then allowing the egg to discard half its skin cell chromosomes — a process similar to meiosis, when cells divide to produce sperm or egg cells. This results in a haploid egg — with a single set of chromosomes — with precisely half the chromosomes of the diploid skin cell — with two sets of chromosomes. At just the right phase of the cell cycle, the new egg is combined with sperm chromosomes through in vitro fertilization.
An embryo then develops with the correct diploid number of chromosomes from each parent.
"We had to show in the mouse that this hypothesis works," Mitalipov said. "Open Philanthropy saw the implications for fertility with a new way of looking into this. The key is inducing haploidy."
