Release date: 2017-08-07
For the first time, scientists have used genetic editing techniques to correct pathogenic mutations in human early embryos. The researchers used the CRISPR-Cas9 system to safely repair genetic mutations that cause hypertrophic cardiomyopathy at the earliest stages of embryonic development, so that genetic defects are not passed on to future generations.
The heavyweight research results were published in Nature, and the research was completed by the Oregon Health and Science University, the Korea Institute of Basic Sciences, the American Salk Institute of Biology, and the Shenzhen National Gene Bank Synthesis and Editing Platform.
Juan Carlos Izpisua Belmonte, professor of the Salk Institute of Biology and author of the study, said: "Thanks to the continuous advancement of stem cell technology and gene editing technology, we have finally begun to repair disease-causing mutations affecting millions of people. In its infancy, even this preliminary research is considered safe and effective."
Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by ventricular muscle hypertrophy. The prevalence is about 1 in 500. It is a global disease and the main cause of sudden death in young and middle-aged athletes. one. Most hypertrophic cardiomyopathy is caused by genetic mutations, and the MYBPC3 gene mutation is the most common genetic mutation. People with mutations in the MYBPC3 gene have a 50% probability of passing it on to their offspring, so the use of gene editing techniques to repair MYBPC3 pathogenic mutations in embryos has brought hope to radically cure this familial genetic disease.
The researchers induced pluripotent stem cells from a skin biopsy donated by HCM males, and developed a CRISPR-Cas9-based gene editing strategy for the stem cells that would specifically target mutations in the MYBPC3 gene. The targeted mutated MYBPC3 gene was cleaved by the Cas9 enzyme, and the donor cell's own DNA repair mechanism repairs the MYBPC3 mutation during the next round of cell division by using the synthetic DNA sequence or a non-mutated copy of the MYBPC3 gene as a template.
In this study, the researchers used normal human eggs and in vitro fertilization of sperm carrying MYBPC3 heterozygous disease-causing mutations to produce fertilized eggs, and injected the CRISPR-Cas9 system component into early embryos. They then analyzed the repair of all cells in the early embryos at the single-cell level to understand how the CRISPR-Cas9 system effectively repairs disease-causing mutations.
Scientists are amazed at the safety and effectiveness of this approach. The results confirmed that not only a high proportion of pathogenic mutations were repaired, but also that the gene repair process did not cause any detectable off-target mutations and genomic instability. Off-target mutations and genomic instability were major problems in gene editing technology. In addition, researchers will develop a more robust editing strategy to ensure consistent mutation repair in all cells.
"Although the repair rate of cells cultured in culture dishes is very low, CRISPR-Cas9 technology seems to be very powerful in correcting MYBPC3 gene mutations in embryonic cells." Researcher Jun Wu said that Jun Wu is also co-author of the paper. The team found that, surprisingly, embryos prioritized the use of endogenous wild-type gene copies as a repair template for editing and repair, achieving extremely high repair efficiency. The research team used the DNA repair mechanism unique to early embryos to successfully repair disease-causing gene mutations.
"Our findings reveal the potential of early embryo editing in the prevention and control of single-gene genetic diseases, and will play an important role in the development and application of gene editing technology," researcher Izpisua Belmonte added.
Source: Sina Pharmaceutical News
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