Scientists have found 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 study at the 39th Annual Meeting of the European Society for Human Reproduction and Embryology (ESHRE), Dr Nada Kubikova from the University of Oxford (UK) said: “Gene editing can fix faulty genes. This process, which usually involves first breaking and then repairing the DNA strand. Our new findings warn that widely used gene-editing technologies can have undesirable and potentially dangerous consequences when applied to human embryos.”
Scientists have found that the DNA of embryonic cells can be manipulated with high efficiency, but, unfortunately, this rarely leads to the changes necessary to correct the defective gene. Most often, the DNA chain breaks forever, 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 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 target DNA regions in 24 of 25 embryos, indicating that CRISPR is highly effective in human embryonic cells. However, only nine percent of the target sites were repaired using a clinically useful homology-guided repair process. Fifty-one percent of broken DNA strands underwent non-homologous end joining, resulting in mutations in which the strands were rejoined. The remaining 40% of broken DNA chains could not be restored. Unrepaired breaks in the DNA strands eventually led to the loss or duplication of large portions of the chromosome, extending from the break to the end of the chromosome. Anomalies of this type affect the viability of the embryos.
Although the results of the study caution against the use of genome editing in human embryos, scientists have received 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.
Inability of embryos to effectively repair damage The DNA revealed by this study may explain why some IVF embryos do not develop. This understanding could lead to improved IVF outcomes, the researchers said.
Next, researchers will look for new ways to protect early embryos from DNA damage, which could lead to potential improvements in fertility treatments. They also plan to explore more gentle gene-editing techniques that avoid breaking strands of DNA, which may be easier for embryos to handle.
“In the future, such techniques may provide the ability to reverse mutations that have plagued families for years. generations, preventing the inheritance of catastrophic diseases,” Dr. Kubikova concluded.