信使RNA（mRNA）疗法近年来在临床应用方面取得了重大进展，这要归功于第一个基于mRNA的医药产品的上市。化学修饰可以改善mRNA的临床效果，但将其载入运输系统是一项常规要求。mRNA纳米医学必须针对特定的治疗目的进行设计，保护核酸并促进跨越生物屏障。聚合物、多肽和阳离子脂质是用于设计mRNA运输系统的主要材料。其中，脂质纳米粒（LNPs）是最先进的，目前在多个领域包括免疫治疗（对抗传染病和癌症）、蛋白质替代、基因编辑和再生医学方面处于临床评估的前沿。本章概述了mRNA传递技术的情况，特别关注LNPs，并介绍了其在临床应用中的最新进展。脂质体是LNPs中临床转化最高的mRNA传递技术，而最近批准了一项利用外泌体制备的治疗性mRNA的临床试验，用于蛋白质替代治疗。全球监管机构批准的第一个mRNA产品是基于LNP的mRNA疫苗，用于抗击病毒感染，特别是2019年冠状病毒疾病（COVID-19）。针对癌症的mRNA疗法的临床应用主要集中于三个策略：通过传递癌细胞抗原或作为辅助剂进行抗癌疫苗接种、mRNA工程的嵌合抗原受体（CARs）和T细胞受体（TCRs），以及抗体和免疫调节剂的表达。癌症免疫疗法，尤其是COVID-19疫苗，是mRNA临床应用的先锋。版权所有©2022 Elsevier Inc.

Messenger RNA (mRNA)-therapies have recently taken a huge step toward clinic thanks to the first mRNA-based medicinal products marketed. mRNA features for clinical purposes are improved by chemical modifications, but the inclusion in a delivery system is a regular requirement. mRNA nanomedicines must be designed for the specific therapeutic purpose, protecting the nucleic acid and facilitating the overcoming of biological barriers. Polymers, polypeptides, and cationic lipids are the main used materials to design mRNA delivery systems. Among them, lipid nanoparticles (LNPs) are the most advanced ones, and currently they are at the forefront of preclinical and clinical evaluation in several fields, including immunotherapy (against infectious diseases and cancer), protein replacement, gene editing and regenerative medicine. This chapter includes an overview on mRNA delivery technologies, with special interest in LNPs, and the most recent advances in their clinical application. Liposomes are the mRNA delivery technology with the highest clinical translation among LNPs, whereas the first clinical trial of a therapeutic mRNA formulated in exosomes has been recently approved for protein replacement therapy. The first mRNA products approved by the regulatory agencies worldwide are LNP-based mRNA vaccines against viral infections, specifically against the 2019 coronavirus disease (COVID-19). The clinical translation of mRNA-therapies for cancer is mainly focused on three strategies: anti-cancer vaccination by means of delivering cancer antigens or acting as an adjuvant, mRNA-engineered chimeric antigen receptors (CARs) and T-cell receptors (TCRs), and expression of antibodies and immunomodulators. Cancer immunotherapy and, more recently, COVID-19 vaccines spearhead the advance of mRNA clinical use.Copyright © 2022 Elsevier Inc. All rights reserved.