Scientists have discovered that human embryonic cells are often unable to repair damage to their DNA. This has important implications for the use of gene editing techniques to remove serious hereditary diseases in embryos, as well as for IVF in general.
Presenting the research at the 39th annual meeting of the European Society of Human Reproduction and Embryology (ESHRE), Dr Nada Kubikova from the University of Oxford (UK) said: “Gene editing can correct defective genes. This is a process that usually involves first breaking and then repairing the DNA strand. Our new findings warn that widely used gene editing technologies may have unwanted and potentially harmful consequences if they are applied to human embryos.”
Scientists have discovered that the DNA of embryonic cells can be manipulated with high efficiency, but unfortunately this rarely leads to the changes needed to correct the defective gene. Most often, the DNA strand is broken permanently, which can potentially lead to additional genetic abnormalities in the embryo.
In an ethically approved study, Dr. Kubikova and her colleagues fertilized donor eggs with donor sperm using intracytoplasmic sperm injection (ICSI) to create 84 embryos. In 33 embryos, they used a special embryo editing technology (CRISPR-Cas9) to create breaks in the two strands that make up the DNA molecule. The remaining 51 embryos were kept as controls.
The researchers found changes in targeted DNA regions in 24 of 25 embryos, indicating that CRISPR is highly effective in human embryonic cells. However, only nine percent of target sites were repaired using the clinically useful homology-directed repair process. Fifty-one percent of broken DNA strands underwent nonhomologous end joining, resulting in mutations in which the strands were rejoined. The remaining 40% of broken DNA strands could not be restored. Unrepaired DNA strand breaks eventually lead to the loss or duplication of large sections of the chromosome, extending from the break site to the end of the chromosome. Anomalies of this type affect the viability of embryos.
Although the study cautions against the use of genome editing in human embryos, the scientists found some positive results suggesting that the risks can be reduced and the ability to successfully remove mutations can be increased by changing the way the genome is edited.
Embryos' inability to effectively repair damage The DNA revealed by this study may explain why some IVF embryos fail to develop. This understanding can lead to improved IVF results, scientists say.
Next, researchers will look for new ways to protect early embryos from DNA damage, which could lead to potential improvements in infertility treatments. They also plan to explore gentler gene-editing techniques that avoid DNA strand breaks, which may be easier for embryos to cope with.
“In the future, such techniques could make it possible to reverse the mutations that have plagued families for years. generations, preventing the inheritance of catastrophic diseases,” concluded Dr. Kubikova.