病毒样颗粒作为mRNA递送载体的研究进展

Advances of virus-like particles as mRNA delivery vectors

摘要:

随着信使核糖核酸(messenger RNA,mRNA)技术的不断发展，mRNA药物在近些年展现出了广阔的应用前景。mRNA自身易被降解且难以直接入胞，因此mRNA递送载体一直是mRNA药物研发的重点之一。尽管脂质纳米颗粒(lipid nanoparticles,LNP)已经广泛应用于mRNA的递送，但LNP倾向于在肝脏聚集，并且重复给药后容易诱发机体炎症反应从而导致组织损伤。相比LNP，病毒样颗粒(virus-like particles,VLP)具有生物相容性高、安全性高的优势，有望为mRNA递送提供新的解决思路。本文从实际应用需求出发，根据VLP实现mRNA递送的几个步骤，即颗粒组装、递送入胞和胞内释放，对该领域的研究进展进行综述，为开发新型VLP递送载体提供依据和设计思路，从而推动VLP载体在mRNA递送领域的发展，为mRNA疗法的研究和应用提供新的可能。

Abstract:

With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.