Groundbreaking study demonstrates promise, controversy of gene editing in embryos

For the first time, scientists said, they corrected a gene mutation linked to inherited heart conditions in human embryos using the approach.

Using the cutting-edge genome-editing technique CRISPR-Cas9 on multiple embryos, the researchers corrected a gene known to cause a type of heart disease called hypertrophic cardiomyopathy that can cause sudden cardiac arrest.

But the new study, published in Nature, suggests that CRISPR might work as an aid to fertility clinic screening for risky inherited diseases, relying on a previously unknown ability of human embryos to swiftly fix their genes. This is earlier in development than previous human embryo editing experiments had tried, and studies in mouse embryos have shown that the technique can eliminate mosaics when the father's genome is targeted.

Following early reports last week that scientists had edited the DNA of human embryos, American researchers have now published their much anticipated paper in the journal Nature.

Boiled down to its simplest explanation, CRISPR-Cas9 works like a pair of scissors to selectively trim out parts of a genome and replace them with new stretches of DNA.

This progress has come over the attempts by the federal government to prevent it by not funding any research that leads to changes in the "germ line" - sperm, cells etc., that transmit genetic information.

Jennifer Doudna, a University of California, Berkeley molecular biologist, told the the San Diego Union-Tribune that the recommendations of the National Academy of Science should be respected, saying the ban on clinical trials ought to continue "until there's broad societal consensus about the value". The phenomenon of "mosaicism" (simultaneous presence of genes in healthy and defective in embryo) could not be avoided, the researchers of the new study have been able to do.

The edited embryos developed similarly to the control embryos, with 50 percent reaching the blastocyst stage, indicating gene editing does not block development, according to the researchers.

"The embryos are really looking for the blueprint", Mitalipov, who directs OHSU's Center for Embryonic Cell and Gene Therapy, said in an interview.

This study was a pre-clinical test created to examine the technique's safety and effectiveness, and while further optimization is needed before clinical trials can be considered, the results are promising. "There is still work to do to improve the efficiency", says Mitalopov.

Around the time the sperm was injected into the eggs, researchers snipped out the gene that causes the disease.

Scientists contacted by KPBS saw these results as a small yet successful step toward the development of new strategies for fighting genetic diseases in future generations. At the same time, the eggs were injected with gene editing tools. Moreover, DSBs in the mutant paternal MYBPC3 gene were preferentially repaired using the wild-type oocyte allele as a template, suggesting an alternative, germline-specific DNA fix response. If the defect was in the woman's genes instead of the man's, then the gene editing trick uncovered by the study wouldn't work, he said.

"We would like to explore a correction for cancer genes particularly BRCA, which is inherited the same way and a single copy can cause breast cancer", he says.

These are valid points, but they don't change the fact that CRISPR-based genome editing offers not only the potential to remove defective genes but also add more desirable ones, which embryo screening does not. He hopes his success in the laboratory will help soothe fears about genetic manipulation of human embryos. "If the law in the United Kingdom was changed to allow genome editing, it would be highly regulated by the Human Fertilisation and Embryology Authority, as is PGD, to ensure it is only used for medical reasons".

The study focused on the genetic mutation that causes hypertrophic cardiomyopathy, which effects an estimated 1 in 500 individuals.

The National Academy of Sciences released a report past year urging caution when using CRISPR to permanently alter inherited genes - exactly the thing done by the new study.

Now, when it comes to using CRISPR to correct gene mutations in embryos, Mitalipov said Tuesday, "We've done some ground work".

In this case, scientists can analyze the embryos in vitro to weed out any with the genetic defect before implantation into the womb. "There is a long road ahead [to the clinic]".

  • Joanne Flowers