Myophosphorylase gene transfer in McArdle's disease myoblasts in vitro

McArdle's disease is due to a genetic deficiency of glycogen phosphorylase and results in a lack of glucose mobilization from glycogen during anaerobi c exercise. A genetic defect in Merino sheep produces a similar picture. We constructed a first-generation adenoviral recombinant containing the full- length human phosphorylase cDNA under the control of the Rous sarcoma virus promoter. Primary myoblast cultures from phosphorylase-deficient human and sheep muscle were efficiently transduced with this vector, resulting in re storation of the phosphorylase activity. A similar correction of the geneti c defect in muscles of McArdle's patients in vivo appears feasible, prefera bly with the use of an adeno-associated viral vector.