Gómez-Aguado Itziar, Rodríguez-Castejón Julen, Vicente-Pascual Mónica, Rodríguez-Gascón Alicia, Solinís María Ángeles, Del Pozo-Rodríguez Ana
Pharmacokinetics, Nanotechnology & Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, 01015 Vitoria-Gasteiz, Spain.
Nanomaterials (Basel). 2020 Feb 20;10(2):364. doi: 10.3390/nano10020364.
The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.
近年来，信使核糖核酸（mRNA）在基因治疗中的应用日益增加，这是因为与质粒DNA相比，它具有独特的特性：瞬时表达、无需进入细胞核且无插入诱变风险。然而，mRNA作为一种治疗工具的临床应用受到其不稳定性和激活免疫反应能力的限制；因此，mRNA化学修饰以及合适载体的设计至关重要。本手稿包括对用于增强体外转录（IVT）mRNA功能和功效的策略的修订，包括优化其稳定性和翻译效率，以及调节其免疫刺激特性。还概述了为保护mRNA和克服细胞内和细胞外屏障以实现成功递送而设计的纳米系统。最后，强调了mRNA纳米药物在针对传染病和癌症的免疫、蛋白质替代、基因编辑和再生医学方面的当前和未来应用。
