An global team of researchers has used CRISPR-Cas9 gene editing - a technique that allows scientists to make precise changes to genomes with relative ease - to correct a disease-causing mutation in dozens of viable human embryos.
The method successfully repaired the error in 42 out of 58 embryos treated, marking a 72.4 percent success rate. Using this approach, embryos had often displayed mosaicism, in which only some of the cells in an embryo are corrected. The researchers didn't notice any "off-target" effects on the DNA, either.
The study's co-authors were part of the Center for Genome Engineering, within the Institute for Basic Science, and Seoul National University in South Korea; the Salk Institute for Biological Studies in La Jolla, California; and BGI-Qingdao and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics in China. "Consent is particularly important when dealing with very vulnerable research subjects, and human embryos are among the most vulnerable of God's creatures".
However, gene editing is a controversial area of study, and the researchers' work included changes to the germ line, meaning the changes could be passed down to future generations. But he notes that worries about "designer babies" - children who have been genetically enhanced, rather than merely correcting disease-causing mutations - may be eased somewhat by the new paper.
But there is no shortage of concerns regarding genome editing. "Now we have shown it is not going to be a big issue, I hope they will reconsider".
In the US, Congress has blocked any clinical trials with the aim of turning an edited IVF embryo into a baby. Injecting CRISPR/Cas9 along with sperm (bottom row) repairs the mutation before DNA replicates, leading to an embryo with all healthy cells. Theoretically, such technology could be used to help parents with a genetic disease or who are carriers of a genetic disease to undergoing selective manipulations of embryos prior to being implanted in the uterus.
The scientists say had the embryo been allowed to mature, the successive generations would have been free from the faulty gene. The higher targeting efficiency "suggests that human embryos employ different DNA fix mechanisms than do somatic or pluripotent cells, probably reflecting evolutionary requirements for stringent control over genome fidelity in the germline", the authors wrote in the paper. Fertility clinics can already screen embryos for the 50-50 chance genetic defects like the one in the study, he noted, and then not use the defective ones in IVF procedures.
The researchers have achieved in vitro fertilization of oocytes female normal by sperm carrying the defective gene. "Our expectation was that this was how embryos would respond. Neither did we modify anything", Mitalipov said.More news: Comparison between investment and gambling
There's wide agreement that more research is needed on the technology itself as well as its ethical implications. Should we take the risk of proceeding with the first full term human pregnancy, not knowing if the technology will have unexpected adverse consequences? "Even though the yield of wild-type [embryos] is higher, there is still room to improve".
In the mean time, though, scientists still have a lot to work out. People with the disease carry a mutation in one of two copies of their MYBPC3 gene. "I don't think it's the start of clinical trials yet, but it does take it further than anyone has before".
"We still have a long road ahead", Mitalipov said, before ever doing this in a human baby. "It's unclear at this point when we would be able to move on", Mitalipov told reporters. As Dibbens puts it: "The study advances our understanding of gene editing technologies and again highlights the need for discussions on what situations gene editing will be used in in the future". When and how will we know that it is time to create a living, breathing human from a modified embryo? "The technique was used to make a correction using existing wild-type maternal genes".
However, in a complete surprise to the researchers, this did not happen. The report said if the technology can not be legally harnessed to prevent more questionable uses - such as the creation of so-called "designer babies" with desirable traits - it should remain off limits. Nonetheless, it suggests that scientists can fix DNA to prevent babies from inheriting diseases that run in a family.
Genetic diseases are a significant cause of healthcare spending and death globally, and many research groups are using CRISPR as a tool to try to combat them. "It is far too early to extrapolate this into any clinical application", Middleton said.
But the researchers say that's actually less of a problem now because the method by which the embryos became disease free did not involve inserting an engineered gene into the DNA code. The researchers have not attempted to add any new genes or change traits, only to correct a disease-causing version of a gene.
For Peter Braude, emeritus professor of obstetrics and gynaecology, King's College London, the "remarkable paper" demonstrates just how rapidly the field of genome editing has progressed since 2015. "One of the major concerns is whether there will be off-target effects". That's encouraging for one potential use of CRISPR in the future as a way to correct inherited genetic disease, says Mitalipov, since the embryo seems to have a built-in, reliable way of repairing the injury caused by splicing out an abnormal gene. But the panel also said, "Do not proceed at this time with human genome editing for purposes other than treatment or prevention of disease and disability".