College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
Adv Drug Deliv Rev. 2023 Sep;200:114990. doi: 10.1016/j.addr.2023.114990. Epub 2023 Jul 7.
RNA therapeutics show a significant breakthrough for the treatment of otherwise incurable diseases and genetic disorders by regulating disease-related gene expression. The successful development of COVID-19 mRNA vaccines further emphasizes the potential of RNA therapeutics in the prevention of infectious diseases as well as in the treatment of chronic diseases. However, the efficient delivery of RNA into cells remains a challenge, and nanoparticle delivery systems such as lipid nanoparticles (LNPs) are necessary to fully realize the potential of RNA therapeutics. While LNPs provide a highly efficient platform for the in vivo delivery of RNA by overcoming various biological barriers, several challenges remain to be resolved for further development and regulatory approval. These include a lack of targeted delivery to extrahepatic organs and a gradual loss of therapeutic potency with repeated doses. In this review, we highlight the fundamental aspects of LNPs and their uses in the development of novel RNA therapeutics. Recent advances in LNP-based therapeutics and preclinical/clinical studies are overviewed. Lastly, we discuss the current limitations of LNPs and introduce breakthrough technologies that might overcome these challenges in future applications.
RNA 疗法通过调节与疾病相关的基因表达，为治疗其他无法治愈的疾病和遗传疾病带来了重大突破。COVID-19 mRNA 疫苗的成功开发进一步强调了 RNA 疗法在预防传染病以及治疗慢性疾病方面的潜力。然而，将 RNA 高效递送至细胞内仍然是一个挑战，需要使用纳米颗粒递药系统（如脂质纳米颗粒（LNP））来充分发挥 RNA 疗法的潜力。尽管 LNP 通过克服各种生物学屏障为 RNA 的体内递供提供了高效平台，但仍存在一些挑战需要解决，以实现进一步的开发和监管批准。这些挑战包括缺乏对肝外器官的靶向递送以及随着重复剂量的增加，治疗效力逐渐丧失。在本文中，我们重点介绍了 LNP 的基本原理及其在新型 RNA 疗法开发中的应用。综述了基于 LNP 的治疗方法的最新进展以及临床前/临床研究。最后，我们讨论了 LNP 的当前局限性，并介绍了可能在未来应用中克服这些挑战的突破性技术。
