动物实验 z-bo 2020-08-28 453

　　Age-related macular degeneration (AMD) affects retinopathy, resulting in blurred or distorted vision and dark spots in the center of vision. It is estimated that one in ten people over the age of 65 suffer from this disease, and the disease will increase with age. AMD is very common among whites and can cause visual distortion and blind spots. Scientists at the Genetic Engineering Center of the Korea Institute of Basic Science (IBS) reported that they used CRISPR-Cas9 technology to perform "gene surgery" on a specific tissue layer that supports the retina of living mice. This research was published in "Genome Research" (click the lower left corner to read the original text), which combines basic research with a mouse model application. The most common retinopathy that causes blindness includes retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. In these diseases, vascular endothelial growth factor (VEGF) secretion is abnormally high. For AMD, VEGF can cause the formation of new blood vessels in the eye, but blood and fluid can also enter the eye and damage the macula (center of the retina). Injecting anti-VEGF drugs is the most common method to treat AMD, but because the affected retinal pigment epithelial cells continue to secrete VEGF, they are injected at least 7 times a year. IBS scientists believe that CRISPR-Cas9 technology can improve this situation. Jin Zhen, head of the Genome Engineering Center, explained: “Injection can only treat symptoms, not the root cause. By editing the VEGF gene, you can treat this disease for a long time.”

　　CRISPR-Cas9 is the basis for precise positioning of specific positions in genes. Cutting and repairing. The CRISPR-Cas9 system works by cutting DNA at a target location. In this case, the VEGF gene is excised. Two years ago, IBS scientists demonstrated that pre-assembled CRISPR-Cas9 or Cas9 ribonucleoprotein (RNP) can be introduced into cells or stem cells to modify target genes. This pre-assembled molecule is immediately effective and can be degraded before an immune response is established. Despite the advantages and success of this method, it is still difficult to introduce pre-assembled molecules, and its therapeutic application is limited. In this study, the team injected CRISPR-Cas9 into the eyes of mice with wet age-related macular degeneration to modify the VEGF gene. They initially discovered that the injection method is more effective than plasmid transfer. Second, the compound decomposed and disappeared within 72 hours. Scientists examined the mouse genome and found that the CRISPR-Cas9 molecule only modifies the VEGF gene and does not affect other genes. They monitored the progress of eye diseases by observing choroidal neovascularization (CNV). CNV is a newly formed blood vessel between the retina and sclera. Common problems of wet macular degeneration. The researchers found that the area of CNV was reduced by 58%. In addition, the side effects of pyramidal dysfunction lasted only 3 days and did not recur 1 week after treatment.

　　KimJin-Soo: "Our method suppresses CNV by turning off the VEGF gene. We hope that surgeons can use this method to treat patients in the future."

　　In the past, CRISPR-Cas9 was often used to repair genetic causes. Genetic Variations in Diseases and Cancers This study proposes a new method for the treatment of non-hereditary degenerative diseases. "We have confirmed that this method is effective in animal models. We hope to conduct preclinical trials."