PDF(Pubmed)
Abstract：
Messenger ribonucleic acid (mRNA) has emerged as a promising molecular preventive and therapeutic approach that opens new avenues for healthcare. Although the use of delivery systems, especially lipid nanoparticles (LNPs), greatly improves the efficiency and stability of mRNA, mRNA tends to accumulate in the liver and hardly penetrates physiological barriers to reach the target site after intravenous injection. Hence, the rational design of targeting strategies aimed at directing mRNA to specific tissues and cells remains an enormous challenge in mRNA therapy. High-throughput screening (HTS) is a cutting-edge targeted technique capable of synthesizing chemical compound libraries for the large-scale experiments to validate the efficiency of mRNA delivery system. In this review, we firstly provide an overview of conventional low-throughput targeting strategies. Then the latest advancements in HTS techniques for mRNA targeted delivery, encompassing optimizing structures of large-scale delivery vehicles and developing large-scale surface ligands, as well as the applications of HTS techniques in extrahepatic systemic diseases are comprehensively summarized. Moreover, we illustrate the selection of administration routes for targeted mRNA delivery. Finally, challenges in the field and potential solutions to tackle them are proposed, offering insights for future development toward mRNA targeted therapy.
摘要：
信使核糖核酸（mRNA）已成为一种有前途的分子预防和治疗方法，为医疗保健开辟了新途径。虽然使用输送系统，特别是脂质纳米颗粒（LNP），大大提高了mRNA的效率和稳定性，mRNA倾向于在肝脏中积累,并且在静脉注射后几乎不穿透生理屏障以到达靶位点。因此，旨在将mRNA引导至特定组织和细胞的靶向策略的合理设计仍然是mRNA治疗中的巨大挑战.高通量筛选（HTS）是一种尖端的靶向技术，能够合成用于大规模实验的化合物文库，以验证mRNA递送系统的效率。在这次审查中,我们首先概述了传统的低吞吐量靶向策略。然后是用于mRNA靶向递送的HTS技术的最新进展，包括优化大型运载工具的结构和开发大型表面配体，并对HTS技术在肝外系统疾病中的应用进行了综述。此外，我们说明了靶向mRNA递送的给药途径的选择。最后,提出了该领域的挑战和解决这些挑战的潜在解决方案，为mRNA靶向治疗的未来发展提供见解。
