Nature reviews 3 back-to-back studies: gene editing of human embryos can lead to severe chromosomal confusion.

Guide: The application of gene editing ultimately depends on THE repair of DNA triggered by targeted double-stranded fracture (DSB)CRISPR-Cas9 genome editing technology is now widely used in genetic modification research in plants and animalsAs a promising technique, it is also expected to be used in clinical applications as a tool to correct pathogenic mutations, such as correcting disease-related alleles in somatic cells and correcting disease-causing mutations in human embryos to reduce the burden of genetic diseases in the fetus and newbornsHowever, the application of gene editing ultimately depends on DNA repair triggered by targeted double-stranded fractures (DSBs)At present, we still know very little about the repair mechanism in human cells, and it varies from cell type to cell typephoto source: Pascal Goetgheluck/Science Photo Library, Nature magazine reviewed and reviewed three studies published in the medical preprinted journal bioRxiv to assess the feasibility of gene correction in early human embryosThe results show that the use of CRISPR-Cas9 to modify the human embryo's genes mutation repair efficiency is low, high mosaic rate, and may cause unnecessary large changes to the target site or near the genomedoi: 10.1038/d41586-020-01906-4, bioRxiv published online June 5 from the Nia Kathykan team at the Francis Crick Institute in London, UKAfter using CRISPR-Cas9 to perform a gene mutation in the embryo poU5F1 (the gene's abnormal expression in adult tissue is associated with tumor development), the loss of hybridity in the edited cells was observedAbout 22 percent of the 18 genome-edited embryos produced unexpected genome editing resultsThe cell spans areas outside the target site of POU5F1, as well as fragments of chromosome 6 where the POU5F1 gene is located, which is missing and rearranged, affecting a large number of DNA fragments around POU5F1in POU5F1 targeted embryo samples, fragment loss/increase in chromosome 6 is widespreadon June 20, the journal published the results of a team led by stem cell biologist Dieter Egli from Columbia University in the United States in the CRISPR-Cas9 study of human embryosThe sperm that formed the embryo carried a mutation that causes blindness in the EYS2 gene, and the researchers tried to correct the mutation using CRISPR-Cas9It was found that the most common DNA repair in embryonic cells was the end connection of microhogenic mediate, which led to non-mosaic recovery of the embryo's reading frame However, about half of the fractures go unrepaired, causing the embryo to lose a large portion of the chromosome son at which EYS is located, sometimes even the entire chromosome Cas9 RNP injected into the two-cell embryo after chromosome loss and chimeric the same day, the United States Oregon Health and Science University reproductive biologist Shoukhrat Mitalipov team found that gene transformation and NHEJ are the two major DNA DSB repair mechanisms in pre-implanted human embryos DSB of mutant allele genes in hybrid human embryos can be repaired by gene conversion in up to 40% of target embryos by using intact wild homologous as a template, while targeted pure gene constellations promote the interaction of non-homogenous end-connections (NHEJ) with gene conversion and lead to embryos with the same in-mutation on both gene constellations Although gene conversion can be used for gene correction, it can also lead to widespread hemillosis (LOH), which poses a serious safety risk THE LOH caused by the genetic transformation of myBP3 embryos, all three studies have shown that CRISPR gene editing can lead to confusion in the embryo chromosomes, resulting in larger DNA deletions and rearrangements, and this result sadds scientists' concerns about the safety of genetic genome editing
References: s chromosomal mayhem s2 Frequent saue-hetozygosityin CRISPR-Cas9-edited early human s Cas9 cleavage in humanembryos .