Crispr Gene Enhancing Can Trigger Undesirable Adjustments in Human Embryos, Research Finds

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Crispr Gene Editing Can Cause Unwanted Changes in Human Embryos, Study Finds

In 2017, a team of researchers led by Shoukhrat Mitalipov, a geneticist at Oregon Health and Science University in Portland, reported that human embryos bearing a mutation could be coaxed into this process without a synthetic template. The researchers created embryos from a union of two cells: a sperm with a mutation that can make it difficult for the heart to pump blood, and an egg with a healthy version of the gene. Dr. Mitalipov and his team used Crispr-Cas9 to cut the broken copy of the gene and see if the intact version would guide the repair. They reported a success of the experiment and published it in the journal Nature.

"In principle, this could be a way of correcting a mutation in a human embryo that contains only a broken copy of a gene," said Dr. Egli.

However, the new findings could cast doubts on the 2017 work, added Dr. Egli added.

The cell study researchers focused on another mutation – one that causes hereditary blindness and affects a different part of the genome – but assumed a similar structure. Using donated sperm that contained a mutation in a gene called EYS, they fertilized eggs with normal copies of EYS and then sent Crispr-Cas9 to remove the mutation.

Several of the cells managed to sew the Crispr-cut pieces of DNA back together with a few minor tweaks, said Dr. Egli.

But about half of the embryos seemed unable to cope with the trauma of the break. The genetic damage failed to heal and eventually forced the cells to tear off large chunks of the chromosome containing the mutated EYS and toss them aside. In some cells the entire chromosome was lost.

"This is not a correction," said Dr. Egli. "That is a completely different result."

Instead of gently getting the cell to edit the genetic "text" it was targeting, the Crispr machinery closed irreparable gaps in the cells' DNA, said Maria Jasin, geneticist at Memorial Sloan Kettering Cancer Center and another author the study. The negative consequences are disproportionately catastrophic. "You were talking about trying to fix a gene and you changed a significant part of the genome," said Dr. Jasin.

Dr. Egli and Dr. Jasin said that this is likely also in Dr. Mitalipov's 2017 article happened, but it went unnoticed. After the team of Dr. Mitalipov had carried out the Crispr-Cas9 treatment, they could no longer detect the mutation in embryos. Dr. Egli and Dr. However, Jasin noted that dumping or destroying a huge segment of chromosomes would technically have erased evidence of the mutation as well. Dr. Mitalipov and his team might have confused deletion with editing.

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