Molecular Biology Interdepartmental Program, University of California, Los Angeles, CA, USA.
Center for Duchenne Muscular Dystrophy at UCLA, University of California, Los Angeles, CA, USA.
J Neuromuscul Dis. 2017;4(2):139-145. doi: 10.3233/JND-170218.
Duchenne muscular dystrophy is caused by mutations in DMD which disrupt the reading frame. Therapeutic strategies that restore DMD's reading frame, such as exon skipping and CRISPR/Cas9, need to be tested in the context of the human DMD sequence in vivo. We have developed a novel dystrophic mouse model by using CRISPR/Cas9 to delete exon 45 in the human DMD gene in hDMD mice, which places DMD out-of-frame. We have utilized this model to demonstrate that our clinically-relevant CRISPR/Cas9 platform, which targets deletion of human DMD exons 45-55, can be directly applied in vivo to restore dystrophin.
杜氏肌营养不良症是由 DMD 基因突变引起的，该突变会破坏阅读框。恢复 DMD 阅读框的治疗策略，如外显子跳跃和 CRISPR/Cas9，需要在体内的人类 DMD 序列背景下进行测试。我们使用 CRISPR/Cas9 技术在 hDMD 小鼠中删除人类 DMD 基因的外显子 45，从而开发了一种新型的肌营养不良小鼠模型，使 DMD 失去框架。我们利用该模型证明了我们的临床相关的 CRISPR/Cas9 平台，该平台靶向人类 DMD 外显子 45-55 的缺失，可直接在体内应用于恢复肌营养不良蛋白。
