Department of Pediatrics, Ludwig Maximilian University of Munich, 80337 Munich, Germany.
Ethris GmbH, RNA Biology, 82152 Planegg, Germany.
Mol Ther. 2019 Apr 10;27(4):794-802. doi: 10.1016/j.ymthe.2018.12.012. Epub 2018 Dec 22.
Promising improvements in the field of transcript therapeutics have clearly enhanced the potential of mRNA as a new pillar for protein replacement therapies. Synthetic mRNAs are engineered to replace mutated mRNAs and to be immunologically inconspicuous and highly stable while maximizing protein expression. Approaches to deliver mRNA into the cellular cytoplasm safely and efficiently have been further developed so that two mRNA-based approaches replacing vascular endothelial growth factor (VEGF) and cystic fibrosis transmembrane conductance regulator (CFTR) have now made it into clinical trials. These studies bring mRNA therapeutics for protein replacement therapy closer to clinical realization. Herein, we provide an overview of preclinical and clinical developments of mRNA therapeutics for liver diseases.
在转录治疗领域取得的显著进展，显然增强了 mRNA 作为新型蛋白质替代疗法支柱的潜力。合成 mRNA 经过设计可替代突变的 mRNA，具有免疫隐匿性和高度稳定性，同时最大限度地提高蛋白质表达水平。为了安全有效地将 mRNA 递送至细胞质中，已经进一步开发了各种方法，现在已有两种基于 mRNA 的方法（用于替代血管内皮生长因子 (VEGF) 和囊性纤维化跨膜电导调节剂 (CFTR)）进入临床试验。这些研究使用于蛋白质替代疗法的 mRNA 疗法更接近临床应用。本文综述了用于肝脏疾病的 mRNA 疗法的临床前和临床进展。
