肌肉萎缩症,基因编辑技术CRISPR z-bo 2020-10-20 349

　　The three research teams used CRISPR to remove certain defective genes in mice with Duchenne muscular dystrophy (DMD), allowing these rodents to make necessary muscle proteins. CRISPR was successfully used to treat adult genetic diseases for the first time.

　　The hot genome editing tool CRISPR has achieved another result-researchers used it to treat severe muscular dystrophy in mice. DMD is caused by dystrophin deficiency or dysfunction. Distrophin is an important part of muscle. Its gene contains 79 protein coding regions, called exons. One exon mutation can cause dystrophin problems. DMD only affects boys, with 1 in 3,500 newborns suffering from the disease, and patients usually live only under 30 years of age. So far, researchers have not found an effective cure for this disease. Facts have proved that it is difficult to provide enough muscle stem cells to enter the correct tissue to prevent the development of this disease. Traditional gene therapy uses viruses to bring good forms of damaged genes into cells, and cannot replace the complete dystrophin gene. The latter is too big. Some gene therapy professionals hope to donate the "micro" dystrophin gene to DMD patients. This provides a short, functional protein that can reduce the severity of the disease. Some companies have developed compounds that allow the cell's DNA reading mechanism to bypass defective exons in the dystrophin gene. The result is a short and functionally important protein. However, these so-called exon skipping drugs cannot convince regulators because they have side effects and can only slightly improve muscle performance in clinical trials.

　　CRISPR is now in people's eyes. This technology was evaluated as a breakthrough by Science magazine in 2015. It uses single-stranded RNA to induce an enzyme called Cas9, which can precisely locate and cut DNA in the genome. The cell then repairs the gap by connecting the damaged strand or using the provided DNA template to create a new sequence. Scientists have used CRISPR technology to correct certain cytogenetic diseases collected from animals or humans, and successfully treated liver diseases in adult mice. In 2014, researchers discovered that the technology can also repair the defective dystrophin gene in mouse embryos.

　　However, it does not seem practical to use CRISPR to treat patients who already have DMD. This is because mature adult muscle cells usually do not divide and therefore lack the DNA repair mechanisms needed to initiate the process of gene addition or modification. However, because CRISPR can be used to remove defective exons, the cell's gene-reading mechanism can produce shortened versions of dystrophin, similar to exon skipping and minigene methods.

　　In the first study, Charles Garthbach, a biomedical engineer at Duke University in Durham, North Carolina, used CRISPR to remove the mutant Exon 23 and the body automatically removed the remaining protein coding regions. Trigger "Sewing". Create a new version of dystrophin that works even if it is shortened. They first used a non-pathogenic adenovirus as a vector to deliver the gene editing system to adult mouse leg muscle cells. The results showed that the level of dystrophin in the legs was restored to a certain extent and muscle strength was restored. increase. They injected the gene editing system into the blood of mice. This time, the muscles of the mice, especially those related to the heart, were improved. Myocardial insufficiency is one of the main direct causes of death in DMD patients. In two other studies, Cheng Long of the University of Texas and Amy Vargas of Harvard University also used a combination of adenovirus and gene editing technology to treat DMD mice. The muscle function of the mice was similar. improve. I find.

　　Gersbach commented: "There is still a lot of work to be done to transform this method into a human cure and verify its safety, but the results of the first batch of trials are exciting."

　　Academia can pass. I don't know if it can, but he emphasized. Although there are ethical controversies about the use of gene editing technology to modify mutant genes in human embryos, there is no controversy about using this technology to modify gene mutations in diseased tissues of patients.

　　This encouraged other researchers with muscular dystrophy. Jerry Mendel of Columbus Jerry Mendel National Children's Hospital said: "This seems to be a very promising clinical treatment." Ronald Korn of Toronto Children's Hospital in Canada emphasized that it occurs in living skeletal muscle. He said the new research is "exciting progress."

　　CRISPR technology has been rated as one of the top ten breakthroughs in science three times in a row in the past three years, and became the first breakthrough in 2015. The magazine believes that the precision, low cost and ease of operation of gene editing technology will have a "revolutionary impact" on research.