In 2017, a team of researchers led by Shoukhrat Mitalipov, a geneticist at the Oregon Health and Science University in Portland, reported that human embryos carrying the mutation could be introduced into the process without needing. synthetic molds. The researchers created embryos from a combination of two cells: sperm carrying mutations that could make it harder for the heart to pump blood and eggs with healthy versions of the gene. Dr. Mitalipov and his team used Crispr-Cas9 to cut a damaged copy of the gene to see if the intact version has repair instructions. They reported the experiment successfully and published it in the journal Nature.
“In principle, this could be a way to repair a mutation in a human embryo with only one damaged copy of the gene,” said Dr Egli.
But the new findings may raise some doubts about the 2017 job, Dr. Egli added.
The Cell researchers focused on another mutation – one that causes hereditary blindness and affects another part of the genome – but has adopted a similar setup. Using donor sperm containing a mutation in a gene called EYS, they fertilized an egg with a normal copy of EYS, then sent it to Crispr-Cas9 for mutation.
Some cells have tried to stitch together the DNA fragments that cut Crispr together with a few small changes, says Dr. Egli.
But about half of embryos do not seem to be able to cope with a rupture injury. The genetic damage cannot heal, eventually forcing the cells to tear off and tossing the majority of the mutant EYS-containing chromosomes aside. In some cells, the entire chromosome is lost.
“It is not an adjustment,” said Dr. Egli. “It is a very different result.”
Instead of gently editing the cell into the genetic “text” it is targeted at, says Maria Jasin, a geneticist at Memorial Sloan Kettering Cancer Center and another author of the study. The negative consequence of this, she added, was disproportionate harm. “They’re talking about trying to fix a gene, and you have a significant portion of the genome altered,” says Dr. Jasin.
Dr. Egli and Dr. Jasin said that this could also happen in Dr. Mitalipov’s 2017 paper, but it went unnoticed. After Dr. Mitalipov’s team undertook Crispr-Cas9 treatment, they were no longer able to detect mutations in the embryo. But Dr. Egli and Dr. Jasin note that, technically, selling or destroying a giant chunk of chromosome would also wipe out evidence of a mutation. Dr. Mitalipov and his team, they say, may have mistaken the deletion for an edit.