First precise genome editing of human embryos triggers praise and alarm

Researchers say that they have used a precise genome-editing technique called base editing to alter the genome of human embryos. The announcement has prompted excitement and caution from scientists and bioethicists. Many say that the work is an impressive step towards clinicians being able to fix disease-causing mutations in embryos. But others worry that the technology could be used to try to create embryos with traits such as superior intelligence.

Dieter Egli, a developmental cell biologist at Columbia University in New York City, and his colleagues posted their results on the bioRxiv preprint server on 1 June1. The study, which was first reported by The New York Times, has not yet been peer reviewed.

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Previous studies had suggested that the use of a standard but less precise form of gene editing in embryos can cause the loss of the edited chromosomes — an effect that made the technology unusable in embryonic cells. The work reported in the preprint is “a conceptual shift … that really has the potential to move the field forwards”, says Emre Seli, a fertility specialist at Yale University in New Haven, Connecticut. “This will go down in history in a positive way — less reckless, more careful and ethical than previous attempts,” says Greg Neely, a genomics researcher at the University of Sydney in Australia.

But some researchers expressed concern about the implications of the work. Hank Greely, a biomedical ethicist at Stanford University in California, worries that affluent individuals might be inspired by the study as a jumping-off point to edit embryos.

“You could set up an [in vitro fertilization] lab and a genetic-testing lab for probably a handful of millions of dollars and start doing this,” says Greely. “And one result might be really sick kids.”

Egli responds that the data in the preprint show that such an effort would be premature because of the risks of applying base editing to embryos.

Gene-edited babies

Members of the genome-editing field still remember the actions of Chinese scientist He Jiankui, who used an early genome-editing tool called CRISPR–Cas9 to adjust the DNA sequence of human embryos in 2018. He then implanted those embryos into two women who went on to give birth to babies. His work provoked widespread outrage among scientists, who said that the technology was too risky to be used in people. He ultimately spent three years in prison for illegal medical practice in China. In an interview published in January, He told The New York Times that he was “very proud” of his work.

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Base editing is a second-generation gene-editing tool that allows scientists to make precise, single-letter changes to DNA. Although base editing can make unwanted genetic changes, it is more reliable than the older CRISPR-based technique, which cuts both strands of DNA and increases the risk of harmful changes to the genome.

Egli and his team used base editing in early-stage human embryos to make single-letter changes in three genes. One, called PCSK9, helps to regulate the levels of ‘bad’ cholesterol in the blood and is already the target of several treatments used to reduce the risk of heart attacks and strokes. The other two genes, called HBG1 and HBG2, are involved in fetal haemoglobin production. Researchers are studying whether these genes can be tweaked to treat certain blood disorders.

Mosaic effects

In PCSK9, the team made a single tweak, changing an A to a G at a specific spot in the genome, which had the effect of switching the gene off. Other naturally occurring versions of the gene that also cause it to turn off have been shown to reduce the risk of coronary heart disease.

For HBG1 and HBG2, the researchers also made a single A-to-G base change. This mimicked a natural mutation that helps to produce a protective type of haemoglobin that can reduce the symptoms of sickle-cell disease and β-thalassaemia.

But the edits did not occur uniformly across cells: some had the adjusted bases, but others retained the original sequence, a phenomenon called mosaicism. Egli says that since the experiments described in the manuscript concluded, his team has improved their procedures to reduce mosaicism. He also says that the technology is not ready for the clinic because the snippet of mRNA used to introduce the DNA editor to the embryo cells caused them to stop dividing. “These base editors — they can have damaging effects on the embryo. So why would you use it if you don’t fully understand that?” he says. In its current form, “you can’t use it. It’s as clear as day and night.”

Concerns and criticism

Several researchers have expressed concerns about the implications of the work. Both Neely and Fyodor Urnov, who studies molecular therapeutics at the University of California, Berkeley, for example, note that in vitro fertilization (IVF) and genetic screening are already used to prevent couples from passing on a genetic condition to their offspring. Editing the genomes of human embryos to treat disease is “a solution in search of a problem”, says Urnov. “In practical terms, therefore, this preprint will solely impact the rapidly growing movement of embryo editors for purposes of ‘baby improvement’.”