Review Article | Open Access

Volume 2024 |Article ID 0032 | https://doi.org/10.34133/bdr.0032

mRNA Delivery Systems Based on Protein Nanocages: How Far Can We Go?

Xinying Wang,^1,2 Ruimin Gao,³ Xuan Wang,⁴ Juan Zhou,^1,2 Xian-En Zhang,⁵ Feng Li ^1,2

¹State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China
²University of Chinese Academy of Sciences, Beijing 100049, China
³Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China
⁴College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430065, China
⁵Faculty of Synthetic Biology, Shenzhen Institute of Advanced Technology, Shenzhen 518055, China

Abstract

Messenger RNA (mRNA) therapeutics hold great potential in the prevention and treatment of many diseases owing to several unique advantages. Delivery of mRNA into target cells is a critical step in mRNA therapy. Efficient and safe delivery systems remain an urgent need. Here, we provide an overview of the current applications of protein nanocages (PNCs), which include different types of PNCs, such as viral capsids, nonviral PNCs, and artificial PNCs, in mRNA delivery. PNCs have the features of uniform size, controllable assembly, modifiable inner and outer surfaces, good biocompatibility, and biodegradability, making them ideal candidates for mRNA delivery. In this review, the properties, loading strategies, and delivery outcomes of each tested PNC are introduced. The challenges faced by PNC-based mRNA carriers are discussed. We also share our perspectives on possible strategies to address these challenges, emphasizing the opportunities brought by emerging technologies and disciplinary convergence.