CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice.,Molecular Therapy

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CRISPR/Cas9-Mediated miR-29b Editing as a Treatment of Different Types of Muscle Atrophy in Mice.
Molecular Therapy ( IF 12.1 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.ymthe.2020.03.005
Jin Li ₁ , Lijun Wang ₁ , Xuejiao Hua ₁ , Haifei Tang ₁ , Rui Chen ₁ , Tingting Yang ₁ , Saumya Das ₂ , Junjie Xiao ₃

Affiliation

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.

中文翻译：

CRISPR/Cas9 介导的 miR-29b 编辑可治疗小鼠不同类型的肌肉萎缩。

肌肉萎缩是骨骼肌质量和力量因各种分解代谢刺激而丧失。目前，临床上除了运动外，尚无有效的治疗方法被证明可以减少肌肉萎缩。在这里，我们报告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-29b 中的生物发生加工位点。在体内，这种基于 CRISPR 的治疗通过激活 AKT-FOXO3A-mTOR 信号通路，防止血管紧张素 II (AngII) 诱导的肌肉萎缩、固定和去神经支配，并防止 AngII 诱导的小鼠心肌细胞凋亡，从而显着增加锻炼能力。我们的工作建立了基于 CRISPR/Cas9 的 miRNA 基因靶向作为治疗肌肉萎缩的潜在持久疗法，并扩展了可用于研究 miRNA 体内功能的策略。

更新日期：2020-03-10

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