But editing human embryos to repair the faulty gene itself has stayed out of reach.
Early human embryos handle that damage badly.
When Egli’s group cut embryo DNA this way before, whole chromosomes or big chunks of them vanished from cells.
Until now, no one had watched edited human embryos keep their chromosomes like this.
It also moves the long-stalled debate over editing human embryos forward with real data, not speculation.
Couples carrying a serious inherited disease can already avoid passing it on. But editing human embryos to repair the faulty gene itself has stayed out of reach.
With IVF, doctors can screen a batch of embryos and transfer one that escaped the bad gene. Rewriting the gene inside the embryo has been the part no one could do safely.
The tool meant to repair one gene kept wrecking whole chromosomes. A new approach seems to dodge that damage. The first results have scientists thrilled and uneasy.
A gentler edit
The research was led by Dieter Egli, a developmental cell biologist at Columbia University.
His lab studies how the earliest human cells repair their DNA. He tried a newer editor on donated embryos.
That editor uses base editing, which swaps one letter of the genetic code for another without slicing through the DNA. Where older tools cut both strands, this one only nicks a single strand.
In one gene, the team flipped a single letter of its code, enough to switch the gene off. The method isn’t new, proven years earlier in a lab paper. But doing it in a living embryo is far harder.
Why CRISPR faltered
CRISPR-Cas9, the standard editing tool, works by cutting straight through both strands of DNA at a chosen spot. In most cells the break heals and the edit sticks.
Early human embryos handle that damage badly. When Egli’s group cut embryo DNA this way before, whole chromosomes or big chunks of them vanished from cells. A 2020 study documented the wreck.
Losing a chromosome can derail development or cause disease. That flaw made the cut-and-repair method look unusable in embryos. Fixing one gene wasn’t worth scrambling the rest.
Editing human embryos
This time the base editor behaved differently. Across 117 edited cells the team checked, the two chromosomes carrying the target genes stayed whole, with no big chunks missing.
Until now, no one had watched edited human embryos keep their chromosomes like this. The edits also landed often, with three-quarters of cells in many embryos carrying the change.
Some embryos grew all the way to the blastocyst stage, the hollow ball of cells that forms around day five. From three, the team grew healthy stem cells that still carried the edit.
Side by side, the difference was hard to miss. Embryos cut with the older tool kept losing chromosomes. The base-edited ones stayed whole and intact.
RNA that stalled embryos
An odd wrinkle turned up in how the editor was delivered. Supplied as messenger RNA, the instructions a cell reads to build a protein, it stalled every one of the 19 embryos within days.
Delivered instead as the finished protein, the editor let embryos grow normally, with about a third reaching the blastocyst stage. The protein wasn’t the problem. Something in the RNA was.
Why the RNA halted them is still a guess. The researchers think the embryo may sense the foreign RNA as a danger and shut down, a self-defense no one had seen in human embryos before.
Why the genes were chosen
These genes weren’t picked to cure anyone. One, PCSK9, helps set the level of so-called bad cholesterol.
People born with that gene switched off carry lower cholesterol and far less heart disease. A long study of such families showed the effect.
The other two are tied to a protective, fetal form of hemoglobin, which carries oxygen in blood. Keeping the body making it into adulthood can ease sickle cell disease and some blood disorders.
Both edits copy changes already found in some healthy people, and both genes are well studied in ordinary cells. Neither would be allowed in a real pregnancy under today’s guidelines.
The technology isn’t ready
For all the promise, the method is nowhere near a clinic. Its biggest snag is mosaicism, in which the edit takes hold in some cells of an embryo but not others, leaving a patchwork.
It showed up in most embryos edited at the one-cell stage, making it hard to know what a child would actually inherit.
The editor also slipped to the wrong spots at times. Delivery stays touchy, since the embryo tolerates the editor only in certain forms.
Egli has said plainly that the technology isn’t ready, and that pushing to a clinic now would be premature.
Repairing genes before birth
News of the preprint – work shared before other scientists have vetted it – drew praise and alarm. Some called it a careful step toward repairing disease genes before birth.
Supporters set it apart from the condemned 2018 experiment in China that produced gene-edited babies. Others feared the opposite.
It could tempt wealthy families to edit embryos before anyone knows it is safe. The worry is enhancements rather than cures, and harm to any resulting children.
Still, the core result is solid. A precise editor changed one DNA letter inside a human embryo without the chromosome loss that doomed earlier methods, and the embryo kept growing.
That gives scientists a safer way to study how our earliest cells repair DNA. It also moves the long-stalled debate over editing human embryos forward with real data, not speculation.
The study is published in the preprint server bioRxiv.
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