Biomedical Translation Research Center, Academia Sinica, Taipei, 11571, Taiwan.
Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Academia Road, Section 2, Taipei, 11529, Taiwan.
J Biomed Sci. 2024 Sep 10;31(1):89. doi: 10.1186/s12929-024-01080-z.
Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases.
实现基于 mRNA 的药物的巨大临床潜力,需要不断开发安全高效传递生物活性制剂的方法,同时避免引发副作用。在这方面,脂质纳米粒已成功用于提高 mRNA 的传递效率,并保护货物免受细胞外降解。封装在脂质纳米粒中是 mRNA 疫苗成功临床应用的关键因素,这确凿地证明了该技术有潜力产生已批准的药物。在这篇综述中,我们首先描述了 mRNA 修饰、新型脂质设计和基于 mRNA 的药物用脂质纳米粒组件的最新进展。然后,我们总结了与 mRNA 治疗剂的临床前和临床开发相关的要点。最后,我们涵盖了与靶向递药系统相关的主题,包括内涵体逃逸和针对免疫细胞、肿瘤和器官的靶向,以及用于 mRNA 疫苗和人类疾病新治疗模式的靶向递药系统。