In November, a Chinese researcher, He Jiankui, used CRISPR-Cas9 gene editing to alter the DNA of embryos for seven couples. The announcement was met by widespread condemnation, investigations and the call for a global moratorium against such research.
Now, Russian molecular biologist Denis Rebrikov told the journal Nature he was considering doing the same thing by the end of this year if he gets approval.
Jiankui used CRISPR to modify the CCR5 genes in the embryos of the Chinese couples. The intention, at least according to He, was to make the babies more resistant to HIV infection. In all seven couples, the fathers had controlled HIV infections, and inactivated CCR5 genes appear to provide some protection against infection. From the point of view of medical necessity, there was no need for the procedure, which was only part of the criticism of it.
In Rebrikov’s case, he wants to disable the gene in embryos that will be implanted into mothers who are HIV-positive. This confers a greater risk of HIV infection to the children than having HIV-positive fathers. The procedure would decrease the risk of passing the virus on to the babies and, according to Rebrikov, would have fewer risks and be more ethically justifiable.
Rebrikov is the director of a genome-editing laboratory at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology in Moscow. He is also a researcher at the Pirogov Russian National Research Medical University, also in Moscow. Rebrikov indicates he has an agreement with an HIV center to recruit HIV-positive women who want to take part in the procedure.
Further complicating the story is that researchers at UC-Berkeley recently published research that suggested—as many feared—disabling the CCR5 gene has unintended side effects. Analyzing 400,000 records in the UK Biobank, they studied the history of children born naturally with the same edits He Jiankui performed. The researchers found that individuals with two mutated copies of the CCR5 gene had a significantly higher death rate between the ages 41 and 78 than people with one or no copies. They also had a four-fold increased risk of dying from the flu. That research was published in the journal Nature Medicine.
Many countries prohibit the implantation of gene-edited embryos. Russia, for example, has a law that bans genetic engineering in most situations. However, as Nature reports, it’s not clear whether or how the ban would be enforced when it comes to gene editing in an embryo. The Russian laws don’t specifically refer to gene editing. Nature also points out that the China law is ambiguous as well.
Rebrikov indicates he plans to ask for approval from three government agencies, including Russia’s health ministry. He told Nature that could take anywhere from one month to two years.
Jennifer Doudna, one of the discoverers of CRISPR and a molecular biologist at the University of California-Berkeley, told Nature, “The technology is not ready. It is not surprising, but it is very disappointing and unsettling.”
Konstantin Severinov, a molecular geneticist who splits his time between Rutgers University and the Skolkovo Institute of Science and Technology near Moscow, recently assisted the Russian government in designing a funding program for gene-editing research. Severinov told Naturethat getting the government approvals might be difficult. For example, he cites Russia’s Orthodox church, which opposes gene editing.
Although Rebrikov argues that there is a clear medical need in his situation, most geneticists do not think enough is known about the safety of gene editing to conduct it in embryos, and the value, even in this situation, does not justify the risk. There is also skepticism about Rebrikov’s conclusions about his own techniques, which he published in the Bulletin of the RSMU, of which he is the editor-in-chief.
Rebrikov claims that his technique disables both copies of the CCR5 gene more than half the time. Both Doudna and Gaetan Burgio, of the Australian National University in Canberra, expressed doubts about Rebrikov’s data, particularly on whether there were off-target gene edits.
At least in Rebrikov’s case, he appears willing to be turned down by regulators.
