A fourth paper describing attempts to correct defective genes in human embryos using CRISPR is about to be published. A report in MIT Tech Review says the results are the most promising so far but the lack of detail means it is not possible to judge whether this really is the case.
It is the first notable attempt at creating genetically modified human embryos in the USA. To date, three previous reports of editing human embryos were all published by scientists in China.
The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR. Until now, American scientists have watched with a mix of awe, envy, and some alarm as scientists in China were 1st to explore the controversial practice.
Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.
Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.
In altering the DNA code of human embryos, the objective of scientists is to show that they can eradicate or correct genes that cause inherited disease, like the blood condition beta-thalassemia. The process is termed “germline engineering” because any genetically modified child would then pass the changes on to subsequent generations via their own germ cells—the egg and sperm.
Some critics say germline experiments could open the floodgates to a brave new world of “designer babies” engineered with genetic enhancements—a prospect bitterly opposed by a range of religious organizations, civil society groups, and biotech companies.
“So far as I know this will be the first study reported in the U.S.,” says Jun Wu, a collaborator at the Salk Institute, in La Jolla, California, who played a role in the project.
The earlier Chinese publications, although limited in scope, found CRISPR caused editing errors and that the desired DNA changes were taken up not by all the cells of an embryo, only some. That effect, called mosaicism, lent weight to arguments that germline editing would be an unsafe way to create a person.
But Mitalipov and his colleagues are said to have convincingly shown that it is possible to avoid both mosaicism and “off-target” effects, as the CRISPR errors are known.
A person familiar with the research says “many tens” of human IVF embryos were created for the experiment using the donated sperm of men carrying inherited disease mutations. Embryos at this stages are tiny clumps of cells invisible to the naked eye.
“It is proof of principle that it can work. They significantly reduced mosaicism. I don’t think it’s the start of clinical trials yet, but it does take it further than anyone has before,” said a scientist familiar with the project.
Mitalipov’s group appears to have overcome earlier difficulties by “getting in early” and injecting CRISPR into the eggs at the same time they were fertilized with sperm.
That concept is similar to one tested in mice by Tony Perry of Bath University. Perry successfully edited the mouse gene for coat color, changing the fur of the offspring from the expected brown to white.