动物造模,基因编辑 z-bo 2020-09-08 438

　　A few days ago, in a research report published in the international journal Nature Biotechnology, researchers at the Perelman School of Medicine at the University of Pennsylvania found that using gene editing to inactivate a protein called PCSK9 can effectively reduce the number of monkeys . I found that I can do it. Cholesterol level in the body.

　　In this study, researchers used gene editing technology to study large animal models for the first time and found that the expression levels of genes related to clinical diseases decreased. Based on the results of this article, it may be hoped that future researchers will develop new therapies for patients with heart disease who are intolerant to PCSK9 inhibitors, and that such drugs/therapy may increase cholesterol levels in the body. Can also be used for confrontation. Generally, PCSK9 protein can inhibit the receptor from over-clearing harmful cholesterol in the liver, and clinically, inhibiting the level of PCSK9 can reduce the harmful cholesterol level in the human body. However, some patients with hypercholesterolemia are intolerant of these drugs, which suggests that gene editing can be used as a treatment for patients with hypercholesterolemia. Researcher Dr. Lili Wang said that most patients have repeated injections of PCSK9 antibodies to treat the disease. Studies have found that the use of gene editing technology can eliminate the need for such treatment for patients who are intolerant of inhibitors.

　　In this article, the researchers designed a homing endonuclease (meganuclease) to specifically recognize and inactivate the PCSK9 gene, and then use an adenovirus vector (AAV) to carry the homing nucleic acid. The endonuclease interferes with the PCSK9 gene in the liver of primates. The researchers found that the PCSK9 levels of animals treated with medium and high doses of AAV vectors were reduced by 45% to 84%, and harmful cholesterol levels were also reduced by 30% to 60%, which has specific clinical significance. I found that sex can be steadily reduced. From the results of molecular analysis of liver biopsy, it was found that gene editing induced 40% to 65% of mutations in the PCSK9 gene. More importantly, the dose of AAV vector used herein can be used in clinical trials for the treatment of patients with hemophilia. Use safely and effectively. Researcher James M. Wilson said that combining AAV with artificial homing endonucleases for editing can generate very impressive data in non-human primates. With more than 30 years of gene therapy experience, we have promoted the translational scientific research of gene editing in vivo, and evaluated the safety and effectiveness of early treatment of non-human primates. Strengthen research.

　　Subsequent researchers will need to conduct more in-depth studies to reduce the toxicity and off-target effects of animal models. In addition to patients with hypercholesterolemia, the data in this article can also encourage the development of treatments that use the same technology. A new treatment method for various liver metabolic abnormalities caused by various other gene mutations.