Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Curr Opin Chem Biol. 2024 Aug;81:102499. doi: 10.1016/j.cbpa.2024.102499. Epub 2024 Jul 13.
This review introduces the typical delivery process of messenger RNA (mRNA) nanomedicines and concludes that the delivery involves a at least four-step SCER cascade and that high efficiency at every step is critical to guarantee high overall therapeutic outcomes. This SCER cascade process includes selective organ-targeting delivery, cellular uptake, endosomal escape, and cytosolic mRNA release. Lipid nanoparticles (LNPs) have emerged as a state-of-the-art vehicle for in vivo mRNA delivery. The review emphasizes the importance of LNPs in achieving selective, efficient, and safe mRNA delivery. The discussion then extends to the technical and clinical considerations of LNPs, detailing the roles of individual components in the SCER cascade process, especially ionizable lipids and helper phospholipids. The review aims to provide an updated overview of LNP-based mRNA delivery, outlining recent innovations and addressing challenges while exploring future developments for clinical translation over the next decade.
这篇综述介绍了信使 RNA（mRNA）纳米药物的典型递药过程，并得出结论：该递药过程至少涉及四个步骤的 SCER 级联，每一步的高效率对于保证高的总体治疗效果至关重要。SCER 级联过程包括选择性器官靶向递药、细胞摄取、内涵体逃逸和细胞质 mRNA 释放。脂质纳米粒（LNP）已成为体内 mRNA 递药的一种先进载体。该综述强调了 LNP 在实现选择性、高效和安全的 mRNA 递药中的重要性。讨论随后扩展到 LNP 的技术和临床考虑因素，详细说明了各个成分在 SCER 级联过程中的作用，特别是可离子化脂质和辅助磷脂。综述旨在提供基于 LNP 的 mRNA 递药的最新概述，概述最近的创新，并在探索未来十年临床转化的发展的同时解决挑战。
