Cells of early human embryos are often unable to repair DNA damage caused by CRISPR/Cas gene editing. Report: Claire Robinson

Scientists have discovered that the cells of early human embryos are often unable to repair damage to their DNA caused by the CRISPR/Cas gene editing process. The researchers say that this has important implications for the proposed use of gene editing to repair mutated genes, which underlie serious inherited diseases, as well as for in vitro fertilisation (IVF) in general.

Commenting on her team’s findings, lead researcher Dr Nada Kubikova from the University of Oxford, UK, said: “Gene editing has the potential to correct defective genes, a process that usually involves first breaking and then repairing the DNA strand. Our new findings provide a warning that commonly used gene editing technologies may have unwanted and potentially dangerous consequences if they are applied to human embryos.
         
“Our results show that the use of CRISPR/Cas9 in early human embryos carries significant risks. We have found that the DNA of embryo cells can be targeted with high efficiency, but unfortunately this rarely leads to the sort of changes needed to correct a defective gene. More often, the strand of DNA is permanently broken, which could potentially lead to additional genetic abnormalities in the embryo.”

The new research was presented at a conference and is not yet peer reviewed and published, but it has already created a worried stir, with the Science Media Centre putting out comments from scientists. While some of the scientists comment that any attempt to use gene editing clinically is “premature” and “clinically problematic”, others suggest that base and prime editing, which are gene editing methods that don’t make double-strand breaks in the DNA, might solve the problems found in this research.

GMWatch sought the opinion of molecular geneticist Dr Michael Antoniou, who uses all types of genetic manipulation techniques, including gene editing, in clinical research. What he told us suggests that Dr Kubikova’s findings likely will kill attempts to carry out human germline editing in humans using CRISPR/Cas – and that attempts to get around the problem by using alternative genetic manipulation methods may also prove problematic. He said, “These findings present serious problems for human germline [heritable] genetic engineering.”

Dr Antoniou said the findings have relevance to some agricultural gene-edited GMOs – certainly to animals and possibly to plants, casting yet more doubt on the viability and safety of these types of GMO. Regarding animals, he said, “Some gene-edited animals are created not by cloning but by injecting the gene-editing tool straight into the fertilized embryo.”

This is how Alison Van Eenennaam made her gene-edited cattle that were genetically manipulated to give birth only to male offspring. The experiment failed, creating chaos in the cattle’s genomes.

Dr Antoniou said this was not surprising, as gene editing the embryo is “like unmanned drone warfare: You can target the missile with apparent success, but it still can cause massive collateral damage”.

As for the alleged promise of base editing and prime editing, he said these methods are unlikely to make the issues go away: “They will also create unintended mutations – just perhaps at a lower level than using CRISPR/Cas to make double-strand DNA breaks. They may reduce but not eliminate the risks to the humans that would result from the editing process. And that level of risk is unacceptable.

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