Human embryos repair single-strand DNA damage but struggle with double-strand breaks

Human embryos effectively repair single-strand DNA damage during early development but do not properly repair double-strand breaks, according to a study.

According to Azure Life Science on the 10th (local time), researchers from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB) and Columbia University in the United States reached this conclusion after conducting the first comparative analysis of how human embryos respond to two types of DNA damage.

The researchers used the gene-editing tool CRISPR-Cas9 to induce double-strand breaks in embryonic DNA and base editing to induce single-strand breaks, then observed the repair responses.

The results showed that early human embryos reliably repaired single-strand damage, while repair of double-strand breaks was markedly less reliable at this stage.

Study first author Štěpán Jeřábek explained, “Early human embryos can effectively repair single-strand DNA damage, whereas repair of double-strand breaks is much less reliable at this developmental stage.”

The researchers also succeeded in isolating stem cells from edited 6-day-old embryos. These stem cells provided enough genetic material for detailed analysis, allowing the researchers to investigate the effects of gene editing more deeply.

The study was conducted in Dieter Egli’s laboratory under the oversight of Columbia University’s ethics committee. Researchers at IOCB Prague contributed to refining a protein-based editing tool that precisely induces single-strand DNA changes.

Michal Doležal, a researcher at IOCB Prague, said, “We confirmed that delivering the editing tool directly into embryonic cells in protein form, rather than as mRNA, is compatible with normal embryonic development.”

The researchers emphasized that the findings show the limitations of gene-editing technology and that continued research is needed.

Jeřábek said, “Our goal is not to develop a way to genetically modify human embryos, but to understand through basic research how DNA repair mechanisms work during early development,” adding, “Although base editing has improved on CRISPR-Cas9 in terms of repair precision, many questions about safety must be answered before clinical use.”

Jan Konvalinka, director of IOCB Prague, said, “Ethical debate surrounding this kind of research is justified and necessary,” adding, “The purpose of basic research is to expand the boundaries of knowledge and help us understand the possibilities and limitations of current technology.”

The findings were published in the international journal Nature.