College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing 100871, China.
Theranostics. 2023 Aug 21;13(13):4667-4693. doi: 10.7150/thno.87316. eCollection 2023.
RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases. The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted the medical value of RNA drugs. However, one of the major challenges in realizing the full potential of RNA drugs is to deliver RNA into specific organs and tissues in a targeted manner, which is crucial for achieving therapeutic efficacy, reducing side effects, and enhancing overall treatment efficacy. Numerous attempts have been made to pursue targeting, nonetheless, the lack of clear guideline and commonality elucidation has hindered the clinical translation of RNA drugs. In this review, we outline the mechanisms of action for targeted RNA delivery systems and summarize four key factors that influence the targeting delivery of RNA drugs. These factors include the category of vector materials, chemical structures of vectors, administration routes, and physicochemical properties of RNA vectors, and they all notably contribute to specific organ/tissue tropism. Furthermore, we provide an overview of the main RNA-based drugs that are currently in clinical trials, highlighting their design strategies and tissue tropism applications. This review will aid to understand the principles and mechanisms of targeted delivery systems, accelerating the development of future RNA drugs for different diseases.
基于 RNA 的疗法在各种医学应用中显示出巨大的潜力，包括癌症、传染病和代谢疾病。最近用于对抗 COVID-19 大流行的 mRNA 疫苗的成功突出了 RNA 药物的医学价值。然而，实现 RNA 药物全部潜力的主要挑战之一是将 RNA 以靶向方式递送至特定的器官和组织，这对于实现治疗效果、减少副作用和提高整体治疗效果至关重要。人们已经进行了许多尝试来追求靶向性，但是缺乏明确的指导原则和共同性的阐明阻碍了 RNA 药物的临床转化。在这篇综述中，我们概述了靶向 RNA 递送系统的作用机制，并总结了影响 RNA 药物靶向递送的四个关键因素。这些因素包括载体材料的类别、载体的化学结构、给药途径以及 RNA 载体的物理化学性质，它们都显著有助于特定的器官/组织趋向性。此外，我们还概述了目前正在临床试验中的主要基于 RNA 的药物，强调了它们的设计策略和组织趋向性应用。这篇综述将有助于理解靶向递送系统的原理和机制，加速针对不同疾病的未来 RNA 药物的开发。
