The research result as “Prevention of Muscle Wasting by CRISPR/Cas9- mediated Disruption of Myostatin in Vivo” completed by researchers from Institute for Nutritional Sciences, SIBS, Chinese Academy of Sciences, has been published on Molecular Therapy on Dec. 5th, 2016. The research has put forward that in order to delay the muscle atrophy in cancer patients, they can use CRISPR to knockout the myostatin in muscular tissue.

Cachexia can be found in a variety of diseases, of which accompanied by cancers is the most common. Cancer cachexia is a kind of consumption syndrome showed in many cancer patients. In this disease, although the patients have enough nutrition, there are still a lot of losses in skeletal muscle. Finally, it results in serious decline in quality of life and survival rate.

In this research, the researchers use the SaCRISPR/Cas9 to knockout the myostatin in muscular to alleviate the effect of cachexia. The reasons to choose the myostatin as the target spot are that: 1) Myostatin is negative regulation factors in muscle growth and development. People who carry myostatin of disfunction mutation have been found. And besides the strong muscle system, there is no serious adverse effect. So the security of target can be ensured. 2) The pre-study evidences that myostatin has critical role in cachexia. However, the monoclonal antibody of myostatin is still in clinical trial. 3) Myostatin is mainly secreted by the muscle cells and main effect mode is autocrine/paracrine manner. So the decrease of myostatin concentration in part muscle microenvironment can keep some muscle function when the cachexia happens.

Based on these reasons, the researchers started the expression of SaCas9 by muscular specific promoter and packed into AAV vectors. Then they observed the significant recovery of skeletal muscle function in cachexia mice model induced by tumor through fixed point injection of gastrocnemius organization in mice targeted Mstn gene (encoding myostatin protein). As a replication experiment, using gene editing specific targeting to knockout the myostatin in muscular tissue can be used as a potential gene therapy for the prevention and treatment of cachexia. Moreover, the improvement of targeting efficiency and targeting security will contribute to the real clinical transformation.

Time: 2016-12-08

Source: SIBS