CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice
CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice
复制标题
CRISPR/Cas9 介导的 miR-29b 编辑治疗小鼠不同类型的肌肉萎缩
DOI：
10.1016/j.ymthe.2020.03.005
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发表时间：
2020-05-06
影响因子：
12.4
通讯作者：
Xiao, Junjie
中科院分区：
文献类型：
--
作者：
Li, Jin;Wang, Lijun;Xiao, Junjie
肌肉萎缩是骨骼肌质量和力量的损失，以响应不同的分解代谢刺激。目前，除了运动外，临床上还没有有效的治疗方法可以减少肌肉萎缩。在这里，我们报告了通过局部注射到腓肠肌或胫骨前肌中的CRISPR/Cas9介导的基因组编辑有效地靶向pre-miR-29 b中的生物合成加工位点。在体内，这种基于CRISPR的治疗通过激活AKT-FOXO 3A-mTOR信号通路预防了血管紧张素II（AngII）、固定和去神经支配诱导的肌肉萎缩，并保护小鼠免受AngII诱导的肌细胞凋亡，从而显著提高了运动能力。我们的工作建立了基于CRISPR/Cas9的靶向miRNA的基因，作为治疗肌肉萎缩的潜在持久疗法，并扩展了体内询问miRNA功能的可用策略。
Muscle atrophy is the loss of skeletal muscle mass and strength in response to diverse catabolic stimuli. At present, no effective treatments except exercise have been shown to reduce muscle atrophy clinically. Here, we report that CRISPR/Cas9-mediated genome editing through local injection into gastrocnemius muscles or tibialis anterior muscle efficiently targets the biogenesis processing sites in pre-miR-29b. In vivo, this CRISPR-based treatment prevented the muscle atrophy induced by angiotensin II (AngII), immobilization, and denervation via activation of the AKT-FOXO3A-mTOR signaling pathway and protected against AngII-induced myocyte apoptosis in mice, leading to significantly increased exercise capacity. Our work establishes CRISPR/Cas9-based gene targeting on miRNA as a potential durable therapy for the treatment of muscle atrophy and expands the strategies available interrogating miRNA function in vivo.