First safe repair of disease-causing gene in human embryos

The Associated Press
Lauran Neergaard

WASHINGTON–Altering human heredity?
In a first, researchers safely repaired a disease-causing gene in human embryos–targeting a heart defect best known for killing young athletes a big step toward one day preventing a list of inherited diseases.
In a surprising discovery, a research team led by Oregon Health & Science University reported yesterday that embryos can help fix themselves if scientists jump-start the process early enough.
It’s laboratory research only–nowhere near ready to be tried in a pregnancy.
But it suggests scientists might alter DNA in a way that protects not just one baby from a disease that runs in the family, but his or her offspring, as well.
And that raises ethical questions.
“I, for one, believe, and this paper supports the view, that ultimately gene editing of human embryos can be made safe,” said Dr. George Daley, a stem cell scientist and dean of Harvard Medical School.
“Then the question truly becomes if we can do it, should we do it?”
Daley, who wasn’t involved in the new research, praised it as “quite remarkable.”
“This is definitely a leap forward,” agreed developmental geneticist Robin Lovell-Badge of Britain’s Francis Crick Institute.
Today, couples seeking to avoid passing on a bad gene sometimes have embryos created in fertility clinics so they can discard those that inherit the disease and attempt pregnancy only with healthy ones, if there are any.
Gene editing in theory could rescue diseased embryos. But so-called “germline” changes altering sperm, eggs, or embryos are controversial because they would be permanent, passed down to future generations.
Critics worry about attempts at “designer babies” instead of just preventing disease.
As well, a few previous attempts at learning to edit embryos, in China, didn’t work well and, more importantly, raised safety concerns.
In a series of laboratory experiments reported in the journal Nature, the Oregon researchers tried a different approach.
They targeted a gene mutation that causes a heart-weakening disease–hypertrophic cardiomyopathy–that affects about 1-in-500 people.
Inheriting just one copy of the bad gene can cause it.
The team programmed a gene-editing tool, named CRISPR-Cas9, that acts like a pair of molecular scissors to find that mutation–a missing piece of genetic material.
Then came the test. Researchers injected sperm from a patient with the heart condition, along with those molecular scissors, into healthy donated eggs at the same time.
The scissors cut the defective DNA in the sperm.
Normally cells will repair a CRISPR-induced cut in DNA by essentially gluing the ends back together.
Or scientists can try delivering the missing DNA in a repair package, like a computer’s cut-and-paste program.
Instead, the newly-forming embryos made their own perfect fix without that outside help, reported Oregon Health & Science University senior researcher Shoukhrat Mitalipov.
We all inherit two copies of each gene, one from dad and one from mom–and those embryos just copied the healthy one from the donated egg.
“The embryos are really looking for the blueprint,” Mitalipov, who directs OHSU’s Center for Embryonic Cell and Gene Therapy, said in an interview.
“We’re finding embryos will repair themselves if you have another healthy copy.”
It worked 72 percent of the time, in 42 out of 58 embryos.
Normally a sick parent has a 50-50 chance of passing on the mutation.
None of the embryos were allowed to develop beyond eight cells, a standard for laboratory research.