CRISPR Brings A New Dawn to Treatment of Muscular Dystrophy

For years, scientists have been looking for a cure for muscular dystrophyIn recent years, researchers have seen a new dawn in gene editing for the treatment of muscular dystrophyRecently, researchers from Canada, the United States and Sweden found that in mice with muscular dystrophy, editing a gene involved in producing a protein that promotes muscle strength through the CRISPR system can alleviate symptomsThe study was published in the journal NatureDOI: 10.1038/s41586-019-1430-xPrevious studies have shown that muscular dystrophy is the result of a mutation in the Lama2 geneThese mutations block the production of certain proteins that are essential for muscle developmentMutations in the Lama2 gene can also cause damage to the myelin of neurons, leading to nerve damageFor now, scientists have been looking for a cure for the genein the new study, scientists have adopted a new method of editing the related gene, Lama1This gene is also involved in the production and development of proteins during muscle production and developmentBut unlike Lama2, it can promote the production of another protein called laminin-alpha1 through gene editing, as well as the production of muscle tissueScientists have shown that Lama2's defects can be compensated for by the overexpression of another type of Lama1 genestaff at the Center for Children's Hospital Research in Toronto, Canada, and their Colleagues in the United States successfully demonstrated in the mouse disease model that the expression of the mice themselves, Lama1, could be enhanced through a CRISPR-dCas9 systemThe researchers selected dCas9 from Staphylococcus aureus and connected it to the viral transcription domain VP64 (a trans-activation factor) and a piece of RNA to form the CRISPR-dCas9 system and load it onto the AAV9 virus vectordCas9 cannot cut DNA directly, but can bind to DNA through RNA-directed locationsOnce there is an activation factor or inhibitor binding to the protein, dCas9 changes into a transcription factor to control gene expressionresearchers first tested artificial activation factors on mouse fibroblasts and selected three of the most effective RNA-directed regulatory parts of the Lama1 geneThe CRISPR system is packaged in aAV9 adenovirus, which has a high affinity for the muscle tissue of an animalPreliminary tests inmice showed that all three RNA guidelines were needed to effectively induce Lama1 expression in the musclesPreventive experiments have shown that the introduction of artificial activation factors and guide adenoviruses into the blood of newborn mice can prevent skeletal muscle degradationThe Lama1 boost improved muscle fibrosis in mice
in addition, the authors also demonstrated the potential for treatment in mice that were already sick: high doses of adenovirus were introduced to mice three-week-size mice, and signs of paralysis not only prevented the disease from progressing, but also significantly improved the activity of mice in the sixth weekresearchers reported positive results in testing gene editing techniques in miceThe degree of fibrosis in mice decreased and the volume of muscle fiber increasedThey also found that treating mice paralysed by symptoms allowed them to stand up and move aroundIn addition, the researchers found that the rate of nerve conduction also accelerated, which is a sign of myelin destruction reversalOf course, this discovery is only the beginning, and more research is needed before technical tests can be carried out on human subjectsbut we have reason to believe that in the near future, muscular dystrophy will be curedResources:s1, CRISPR used to reduce the symptoms of theof CRISP R dystrophy in mice models The original title of the : Nature: Aminomal detrophy can be completed? CRISPR Brings New Dawn of Treatment