生殖细胞,遗传疾病 z-bo 2020-09-17 344

　　Journal Cellesearch has published online results of a joint study conducted by the Lee Jinson research group and Woolie Gun research group of the Shanghai Institute of Biological Sciences and the Tanfuchu research group of Peking University. Genetic defects in sperm stem cells are repaired, resulting in completely healthy offspring. Experts believe that this research provides new ideas for human gene therapy. The way to completely cure genetic diseases is to repair the altered genetic material in reproductive cells through gene therapy, and pass the correct genetic material to the next generation to create healthy individuals and eliminate genetic defects in the population. It is to eliminate it completely. However, the existing gene recombination methods cannot effectively edit the genes of germ cells.

　　Li Jinsong’s research team proved for the first time that CRISPR-Cas9 technology can be effectively used to treat genetic diseases. There are two problems with this direct embryo injection method. One is that the probability of neonatal mice to heal is reduced by about 30%, and the other is that there are fewer experimental off-target phenomena. In order to better solve these problems, the researchers obtained sperm stem cells with pure genetic mutations from the testes of cataract mice. The researchers transferred CRISPR-Cas9 to sperm stem cell lines and established a series of cell lines derived from single sperm stem cells through single cell expansion. At the same time, the researchers conducted a detailed analysis of these cell lines and cell lines that meet the following three transplant conditions. The first confirmed that both mutation sites had been repaired by genotyping, and the second confirmed that the off-target site sequence or the whole genome sequence predictably had no off-target problems. Third, specific imprinted gene methylation identification or whole genome methylation sequence confirms that the repaired sperm stem cells maintain normal epigenetic characteristics. Finally, after transplanting these "high-quality" cells into the testes of recipient mice that had exhausted their germ cells, the researchers obtained 100% fully healthy mice.