Marano Nicholas, Guner Liza Elif, Riley Rachel S, Holaska James M
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
Rowan-Virtua School of Translational Biomedical Engineering and Sciences, Rowan University, Stratford, NJ 08084, USA.
Int J Mol Sci. 2025 Aug 12;26(16):7774. doi: 10.3390/ijms26167774.
Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in . Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs have been studied for decades and have recently been used clinically for vaccination and treatment of a myriad of diseases. Here, we show that the treatment of emerin-null myogenic progenitors with LNPs encapsulating emerin mRNA causes robust emerin protein expression that persists for at least 4 days. The treatment of differentiating emerin-null myogenic progenitors with 2.5 pg/cell emerin LNPs significantly improved their differentiation. The toxicity profiling of emerin mRNA LNP (EMD-LNP) dosing shows little toxicity at the effective dose. These data support the potential use of EMD-LNPs as a viable treatment option and establishes its utility for studying EDMD pathology.
埃默里-德赖富斯肌营养不良症1型（EDMD1）由……中的突变引起。大多数EDMD1患者缺乏可检测到的emerin表达。他们会出现骨骼肌萎缩、关节挛缩和心脏传导缺陷等症状。目前，医生依赖于治疗患者症状，而未解决根本原因——缺乏功能性emerin蛋白。因此，需要恢复emerin蛋白表达以改善患者预后的治疗方法。一种方法是将emerin mRNA或蛋白直接递送至受影响组织以恢复组织稳态。在此，我们评估了脂质纳米颗粒（LNPs）将emerin mRNA递送至患病细胞的效用。LNPs已被研究数十年，最近已在临床上用于疫苗接种和多种疾病的治疗。在此，我们表明用包裹emerin mRNA的LNPs处理emerin缺失的成肌祖细胞会导致强大的emerin蛋白表达，该表达持续至少4天。用2.5 pg/细胞的emerin LNPs处理正在分化的emerin缺失的成肌祖细胞显著改善了它们的分化。emerin mRNA LNP（EMD-LNP）给药的毒性分析表明在有效剂量下几乎没有毒性。这些数据支持EMD-LNPs作为一种可行治疗选择的潜在用途，并确立了其在研究EDMD病理学方面的效用。
