Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for in vivo gene editing. Fueled by the recent advancements in both fields, this review aims to provide a comprehensive overview of the basic characteristics of EV and LNP-based NA delivery systems, from EV biogenesis to structural properties of LNPs. It addresses the primary challenges encountered in utilizing these nanocarriers from a drug formulation and delivery perspective. Additionally, biodistribution profiles, in vitro and in vivo transfection outcomes, as well as their status in clinical trials are compared. Overall, this review provides insights into promising research avenues and potential dead ends for EV and LNP-based NA delivery systems.

中文翻译：

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细胞外囊泡与脂质纳米颗粒在核酸递送中的对比


细胞外囊泡 （EV） 越来越多地被研究用于递送核酸 （NA） 治疗药物，利用它们在细胞间信号传导中运输 NA 和基于蛋白质的货物的天然作用。它们的合成对应物脂质纳米颗粒 （LNP） 在过去几十年中已作为 NA 载体开发，最终批准了几种上市配方，例如 patisiran/Onpattro® 和 mRNA-1273/BNT162 COVID-19 疫苗。LNP 的成功激发了开发针对肝外器官的创新技术的努力，并提供新的治疗方式，例如体内基因编辑工具。在这两个领域最新进展的推动下，本综述旨在全面概述基于 EV 和 LNP 的 NA 递送系统的基本特征，从 EV 生物合成到 LNP 的结构特性。它从药物配方和递送的角度解决了利用这些纳米载体时遇到的主要挑战。此外，还比较了生物分布概况、体外和体内转染结果以及它们在临床试验中的地位。总体而言，本综述为基于 EV 和 LNP 的 NA 递送系统提供了有前途的研究途径和潜在死胡同的见解。