myoDN as a potential nucleic acid drug for disease-related muscle wasting

myoDN as a potential nucleic acid drug for disease-related muscle wasting

Tomohide Takaya.

Graduate School of Medicine, Science and Technology, Shinshu University, Japan.

第7回日本心血管協会学術集会 (オンライン), 2022/05/15 (招待講演).


Skeletal muscle wasting is a complication in various diseases such as cancer, chronic kidney disease, diabetes, and heart failure. As muscle loss is a risk factor for prognosis of these diseases, prevention of muscle atrophy and improvement muscle formation are clinically important. Myogenic precursor cells, myoblasts, are responsible for regeneration and hypertrophy of myofibers; however, their abilities decline with aging and diseases. Thus, the molecule activating myoblasts can be a candidate drug against muscle wasting. We recently identified that an 18-base single-strand DNA, named myogenetic oligodeoxynucleotide (myoDN), serves as an anti-nucleolin aptamer (antidot mimic) and promotes myogenic differentiation through potentiating p53 signaling pathway. myoDN successfully recovered myogenic abilities of the myoblasts isolated from diabetic patients and the myoblasts exposed cancer-released factors. It demonstrates that myoDN would be applicable for diabetes-associated muscle loss and cancer cachexia. Furthermore, accumulating evidences indicate that myoDN suppresses inflammatory responses initiated by cytokines. myoDN would provide a nucleic acid drug seed for disease-related muscle wasting associated with chronic inflammation.