动物实验,渐冻症 z-bo 2020-09-14 448

　　Researchers at the University of Illinois at Urbana-Champaign have developed a new CRISPR gene editing method that permanently inactivates the mutant gene that causes hereditary amyotrophic lateral sclerosis (ALS). Mouse model studies have shown that this new therapy can slow down disease progression in ALS mice, improve muscle function and extend their lifespan. ALS, also called gradual freezing syndrome, is a fatal motor neuron disease. The etiology of the disease is very complex, and superoxide dismutase 1 (SOD1) gene mutation is considered to be one of the key pathogenic factors. Studies have shown that about 20% of hereditary ALS is caused by this genetic mutation. Currently, there is no cure for ALS, and gene editing that invalidates the expression of the mutant SOD1 gene is considered a promising treatment. However, due to the size limitation of the adeno-associated virus (AAV) vector widely used in gene therapy, this method has not yet been fully applied.

　　This time, the research team developed a transfer system through intain. This effectively solves the problem of the limited carrying capacity of AAV carriers, and can deliver cytosine-based editors in vivo. This system allows researchers to permanently inactivate mutant genes by introducing meaningless replacement codes.

　　The results of the mouse model study confirmed the effectiveness of the system. Compared with control mice, the disease progression of the treated ALS mice was significantly slowed, and the time from the late stage to the end of the disease increased by 85%. The rate of muscle atrophy in these mice was reduced and muscle function improved. The researchers point out that their work extends the functionality of a single editor and proves its potential in gene therapy. ALS is only the first application target of the new tool, and its application in the treatment of Duchenne muscular dystrophy and spinal muscular atrophy is currently being studied.