Lipid nanoparticles (LNPs) are the most versatile and successful gene delivery systems, notably highlighted by their use in vaccines against COVID-19. LNPs have a well-defined core–shell structure, each region with its own distinctive compositions, suited for a wide range of in vivo delivery applications. Here, we discuss how a detailed knowledge of LNP structure can guide LNP formulation to improve the efficiency of delivery of their nucleic acid payload. Perspectives are detailed on how LNP structural design can guide more efficient nucleic acid transfection. Views on key physical characterization techniques needed for such developments are outlined including opinions on biophysical approaches both correlating structure with functionality in biological fluids and improving their ability to escape the endosome and deliver they payload.

脂质纳米颗粒 (LNP) 是最通用、最成功的基因传递系统，尤其突出的是它们在 COVID-19 疫苗中的应用。LNP 具有明确的核壳结构，每个区域都有自己独特的组成，适用于广泛的体内交付应用程序。在这里，我们讨论 LNP 结构的详细知识如何指导 LNP 配方，以提高其核酸有效负载的递送效率。详细阐述了 LNP 结构设计如何指导更有效的核酸转染。概述了此类开发所需的关键物理表征技术的观点，包括对生物物理方法的看法，这些方法将生物流体中的结构与功能相关联，并提高其逃逸内涵体和传递有效负载的能力。