Liang Huiting, Xing Yun, Wang Kexin, Zhang Yaping, Yin Feng, Li Zigang
Pingshan Translational Medicine Center, Shenzhen Bay Laboratory Shenzhen 518118 China
State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Shenzhen 518055 China
RSC Chem Biol. 2025 Feb 26;6(5):666-677. doi: 10.1039/d4cb00295d. eCollection 2025 May 8.
mRNA-based therapies have broad applications in various disease treatments and have been applied in protein replacement therapy, gene editing, and vaccine development. Numerous research studies have been carried out aiming to increase the stability of mRNA, improve its translational efficiency, and reduce its immunogenicity. However, given mRNA's large molecular size and strong electronegativity, the safety and efficient delivery of mRNA into the target cells remains the critical rate-limiting step in current mRNA drug development. Various nanocarriers, such as liposomes, lipid nanoparticles, polyetherimide, and mesoporous silica nanoparticles, have been employed for mRNA delivery in the past few decades. Among them, peptides have demonstrated great potential as promising carrier candidates for mRNA delivery due to their high cell membrane permeability, good biocompatibility, definite chemical structure, and ease of preparation. Here, peptide-based mRNA delivery systems are systematically analyzed, including their construction strategies, mechanisms of action in mRNA delivery, and the application limitations or challenges. It is hoped that this review will guide the design, optimization, and applications of peptide carriers in mRNA-based drug development.
基于信使核糖核酸（mRNA）的疗法在各种疾病治疗中具有广泛应用，并已应用于蛋白质替代疗法、基因编辑和疫苗开发。为了提高mRNA的稳定性、改善其翻译效率并降低其免疫原性，人们已经开展了大量研究。然而，鉴于mRNA的大分子尺寸和强负电性，将mRNA安全有效地递送至靶细胞仍然是当前mRNA药物开发中的关键限速步骤。在过去几十年中，各种纳米载体，如脂质体、脂质纳米颗粒、聚醚酰亚胺和介孔二氧化硅纳米颗粒，已被用于mRNA递送。其中，肽因其高细胞膜通透性、良好的生物相容性、明确的化学结构和易于制备等特点，作为有前景的mRNA递送载体候选物展现出巨大潜力。在此，对基于肽的mRNA递送系统进行了系统分析，包括其构建策略、mRNA递送中的作用机制以及应用限制或挑战。希望这篇综述能指导肽载体在基于mRNA的药物开发中的设计、优化和应用。
