A research team in China has created genetically modified human embryos using the gene-editing technique CRISPR/Cas9, according to a report in the online journal Protein & Cell.

The experiments were conducted by a research team led by Junjiu Huang of Sun Yat-sen University in Guangzhou, China.

Human germline modification is widely considered unethical for both safety and social reasons. Using germline modification techniques to create a human being is prohibited by more than 40 countries and several international human rights treaties.

Responding to the research report, The Center for Genetics and Society (CGS) is calling for a halt to experiments aimed at the creation of genetically modified human beings.

“No researcher has the moral warrant to flout the globally widespread policy agreement against altering the human germline,” commented Marcy Darnovsky, PhD, CGS Executive Director.

“The medical risks and social dangers of human germline modification cannot be overstated. Creating genetically modified human beings could easily lead to new forms of inequality, discrimination, and societal conflict.”

Clinical applications premature

The research tried to head off such concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics, according to an article in Nature News. “The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.”

The genetic changes the scientists intended were actually made in only a small number of the embryos they used, and they found a large number of “off target” effects.

Plans for future research

Nonetheless, the researchers don’t plan to give up. According to news reports, at least four other groups in China are currently exploring gene editing of human embryos.

The Protein & Cell paper “demonstrates the enormous safety risks that any attempt to produce a genetically modified human being would entail, and underlines the urgency of working to forestall such efforts,” Darnovsky said. CGS is concerned that the development of gene editing makes germline modification so technically easy that anyone with basic molecular biology training has the capability to attempt it.

“We can no longer consider this a far-off prospect to be dealt with in the future,” Darnovsky said. “We need to act immediately to strengthen the global policy agreements that put human germline modification off limits.”

Abstract of CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBBlocus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.