免疫原性
高尿酸血症
痛风
尿酸氧化酶
医学
尿酸
免疫学
药理学
抗体
内科学
作者
Zhenglan Ban,Madi Sun,Huihong Ji,Quanxin Ning,Chuanxu Cheng,Tongfei Shi,Minghao He,Xuenian Chen,Huanfen Lu,Xuan He,Chen-Yang Guo,He Yan,Dan Shao,Yi He
标识
DOI:10.1016/j.jconrel.2024.06.042
摘要
Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases.
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