Full-length dystrophin restoration via targeted genomic integration by AAV-CRISPR in a humanized mouse model of Duchenne muscular dystrophy

This study applies targeted Cas9-based gene insertion strategies for the correction of full-length dystrophin in a pre-clinical humanized mouse model of Duchenne muscular dystrophy. Following intramuscular or intravenous delivery, full-length dystrophin is restored in skeletal and cardiac muscle. High-throughput unbiased sequencing to characterize and quantify gene-editing outcomes in genomic DNA and cDNA transcripts of treated mice.

本研究针对杜氏肌营养不良症（Duchenne muscular dystrophy）的临床前人源化小鼠模型，采用靶向Cas9介导的基因插入策略对全长抗肌萎缩蛋白（dystrophin）进行校正。经肌肉内或静脉内递送后，骨骼肌与心肌中的全长抗肌萎缩蛋白水平得以恢复。本研究采用高通量无偏测序技术，对经处理小鼠的基因组DNA及cDNA转录本中的基因编辑结果进行定性与定量分析。