Transcriptomic profile of three-dimensional tissue-engineered human skeletal muscle model of Pompe disease and recombinant protein therapy

Pompe disease (glycogen storage disease type II, or acid maltase deficiency) is an autosomal-recessive disorder of metabolism caused by mutations in the lysosomal hydrolase, acid alpha-glucosidase gene (GAA), resulting in progressive muscle atrophy. The current standard of care treatment, enzyme replacement therapy, consists of delivering recombinant human GAA (rhGAA) to reduce muscle glycogen and improve patient quality of life. With the aim of developing in vitro systems to study human disease and test therapies, we applied RNA sequencing to 3D tissue-engineered human skeletal muscle to compare healthy, (infantile onset) Pompe disease, and rhGAA-treated Pompe engineered tissues. Overall design: High throughput sequencing of RNA obtained from healthy, Pompe disease, rhGAA treated Pompe disease engineered skeletal muscle

庞贝病（Pompe disease，又称Ⅱ型糖原贮积症或酸性麦芽糖酶缺乏症）是一种常染色体隐性代谢紊乱性疾病，由溶酶体水解酶酸性α-葡萄糖苷酶基因（GAA）突变引发，可导致进行性肌肉萎缩。当前临床标准治疗方案为酶替代疗法，通过递送重组人酸性α-葡萄糖苷酶（rhGAA）以降低肌肉糖原水平、改善患者生活质量。为开发用于研究人类疾病及测试治疗手段的体外系统，本研究对三维组织工程化人骨骼肌开展RNA测序（RNA sequencing），以对比健康工程化骨骼肌、婴儿起病型庞贝病工程化骨骼肌及经rhGAA治疗的庞贝病工程化骨骼肌的转录组特征。
整体实验设计：对取自健康工程化骨骼肌、婴儿起病型庞贝病工程化骨骼肌、经rhGAA治疗的庞贝病工程化骨骼肌的RNA进行高通量测序（High throughput sequencing）。