“People who have thalassemia, they get sicker and sicker as they go on because they don’t have normal red blood cell function, and it gets harder to treat,” Saltzman said. “Here, we’re correcting the gene very early in development, so you see more benefits because they don’t get sick.”
One advantage of this technique, said the researchers, is that it can performed in a living animal, while other gene-editing procedures have mostly been limited to cells in a petri dish. Unlike technologies such as CRISPR — often referred to as a “genetic scissors” — the Yale researchers’ technique is a chemical process, so repair of the targeted gene is more exact and results in fewer off-target effects.
Two challenges the researchers faced were the small size of their target and making sure the therapy would work after only one injection, as multiple injections to a fetus greatly increase risk of harm. For this, David H. Stitelman, M.D., an assistant professor of pediatric surgery, brought his expertise in accessing fetal stem cells.
“You have to catch these cells while they are in a state of massive proliferation, so this is literally a once-in-a-lifetime opportunity,” Stitelman said.
The study’s first author, Adele Ricciardi, an M.D./Ph.D. student, said the team is now looking at how their technique can treat other inherited single-gene disorders, such as cystic fibrosis and sickle cell.
“If a baby could be born with a lower burden of disease — or no disease whatsoever — that would have a profound impact on that child’s life as well as the family,” Ricciardi said.
Additional study authors include Raman Bahal, James S. Farrelly, Elias Quijano, Anthony H. Bianchi, Valerie L. Luks, Rachael Putman, Francesc Lopez-Giraldez, Suleyman Coskun, Eric Song, Yanfeng Liu, Wei-Che Hsieh, and Danith H. Ly.