基因沉默
骨骼肌
小干扰RNA
RNA干扰
心肌
功能基因组学
心肌细胞
生物
寡核苷酸
肌生成抑制素
细胞生物学
药理学
生物信息学
基因
内分泌学
生物化学
转染
核糖核酸
基因组学
基因组
作者
Annabelle Biscans,Jillian Caiazzi,Nicholas McHugh,Vignesh Hariharan,Manish Muhuri,Anastasia Khvorova
标识
DOI:10.1016/j.ymthe.2020.12.023
摘要
Oligonucleotide therapeutics hold promise for the treatment of muscle- and heart-related diseases. However, oligonucleotide delivery across the continuous endothelium of muscle tissue is challenging. Here, we demonstrate that docosanoic acid (DCA) conjugation of small interfering RNAs (siRNAs) enables efficient (~5% of injected dose), sustainable (>1 month), and non-toxic (no cytokine induction at 100 mg/kg) gene silencing in both skeletal and cardiac muscles after systemic injection. When designed to target myostatin (muscle growth regulation gene), siRNAs induced ~55% silencing in various muscle tissues and 80% silencing in heart, translating into a ~50% increase in muscle volume within 1 week. Our study identifies compounds for RNAi-based modulation of gene expression in skeletal and cardiac muscles, paving the way for both functional genomics studies and therapeutic gene modulation in muscle and heart.
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