Zhu Pei, Wu Furen, Mosenson Jeffrey, Zhang Hongmei, He Tong-Chuan, Wu Wen-Shu
Division of Hematology/Oncology, Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.
Mol Ther Nucleic Acids. 2017 Jun 16;7:31-41. doi: 10.1016/j.omtn.2017.02.007. Epub 2017 Feb 28.
Muscle stem cells (MuSCs) hold great therapeutic potential for muscle genetic disorders, such as Duchenne muscular dystrophy (DMD). The CRISP/Cas9-based genome editing is a promising technology for correcting genetic alterations in mutant genes. In this study, we used fibrin-gel culture system to selectively expand MuSCs from crude skeletal muscle cells of mdx mice, a mouse model of DMD. By CRISP/Cas9-based genome editing, we corrected the dystrophin mutation in expanded MuSCs and restored the skeletal muscle dystrophin expression upon transplantation in mdx mice. Our studies established a reliable and feasible platform for gene correction in MuSCs by genome editing, thus greatly advancing tissue stem cell-based therapies for DMD and other muscle disorders.
肌肉干细胞（MuSCs）在治疗肌肉遗传性疾病方面具有巨大的治疗潜力，如杜氏肌营养不良症（DMD）。基于CRISP/Cas9的基因组编辑是一种有前景的技术，可用于纠正突变基因中的遗传改变。在本研究中，我们使用纤维蛋白凝胶培养系统从mdx小鼠（一种DMD小鼠模型）的粗制骨骼肌细胞中选择性扩增MuSCs。通过基于CRISP/Cas9的基因组编辑，我们纠正了扩增的MuSCs中的肌营养不良蛋白突变，并在将其移植到mdx小鼠后恢复了骨骼肌肌营养不良蛋白的表达。我们的研究建立了一个通过基因组编辑在MuSCs中进行基因校正的可靠且可行的平台，从而极大地推动了基于组织干细胞的DMD和其他肌肉疾病的治疗。
