Using CRISPR to create an HLA matched sibling for treating Fanconi Anemia

“After their daughter was diagnosed with Fanconi anemia at 9 months old, Jessica and Keith met other families who had children with the condition and who had unsuccessfully sought out stem cell transplants from unrelated donors. The transplanted cells, called hematopoietic stem cells, had failed to take root in the patients’ bones and replace their diseased cells.

Over time, success rates in stem cell transplants from unrelated donors have improved. But experts say a transplant from a sibling — either with cells from their bone marrow or taken from umbilical cord blood at birth — remains the best option for patients with Fanconi and a handful of other inherited diseases.

It’s why some families try to have another child who could be a donor.

The first savior sibling was born in 2000, also to help save an older sister with Fanconi anemia, or FA. But these rare cases are still debated. There are questions about whether the donor child undergoes any physical harm or will suffer from feeling he or she was born for, crudely speaking, spare parts.

Jessica and Keith had always planned to have a second child, even before their daughter’s diagnosis. And to avoid having another child with FA, they knew they would have to make embryos through IVF and screen them through a process called preimplantation genetic diagnosis, or PGD. The idea is to make sure an embryo has the healthy number of chromosomes and no disease-causing mutations before a pregnancy is started.

With their daughter’s disease, Jessica and Keith wanted to identify an embryo that was not only free of FA, but that could be a “match.” That would be the embryo they would transfer to Jessica’s womb in hopes it would implant and produce a child.

When clinicians look for a suitable donor — whether for bone marrow or another tissue like a kidney — they’re looking for someone whose immune proteins most closely resemble those of the recipient. That way, they reduce the odds that the recipient’s immune system or the transplant will recognize the other as foreign and revolt.

Siblings have about a 25% chance of having the same group of immune proteins, called an HLA complex. In other words, statistically, 1 in 4 embryos made by Jessica and Keith would be a “match” for their daughter. Three out of four of their embryos would be free of Fanconi anemia. So together, only 3 of 16 embryos they created would make an ideal donor. Technically, the odds were even lower because some embryos would not have a healthy number of chromosomes.

“Some people get it on the first cycle, and it’s hallelujah,” said Dr. Ilan Tur-Kaspa, Jessica and Keith’s fertility doctor and the president and medical director of the Institute for Human Reproduction in Chicago, who has proposed guidelines for these cases. “Some people it takes two, three, four, five cycles.”

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