Lung-Selective Delivery of mRNA-Encoding Anti-MERS-CoV Nanobody Exhibits Neutralizing Activity Both In Vitro and In Vivo

编码抗 MERS-CoV 纳米抗体的 mRNA 的肺选择性递送在体外和体内均表现出中和活性

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作者:Yuhang Zhang, Chongyu Tian, Xinyang Yu, Guocan Yu, Xuelian Han, Yuan Wang, Haisheng Zhou, Shuai Zhang, Min Li, Tiantian Yang, Yali Sun, Wanbo Tai, Qi Yin, Guangyu Zhao

Conclusions

Extensive in vitro and in vivo evaluations demonstrate the LNP-mRNA-NbMS10 system's potential as a scalable, cost-effective, and adaptable alternative to current MERS-CoV therapies. This innovative platform offers a promising solution for preventing and treating respiratory infections, and countering emerging viral threats.

Methods

An mRNA-encoding nanobody NbMS10 (mRNA-NbMS10) was engineered for enhanced stability and reduced immunogenicity. This mRNA was encapsulated in lung-selective LNPs using microfluidics to form the LNP-mRNA-NbMS10 system. Efficacy was assessed through in vitro assays and in vivo mouse studies, focusing on antigen-binding, neutralization, and sustained nanobody expression in lung tissues.

Results

The LNP-mRNA-NbMS10 system expressed the nanobody in vitro, showing strong antigen-binding and significant MERS-CoV pseudovirus neutralization. In vivo studies confirmed selective lung mRNA delivery, with high nanobody expression sustained for up to 24 h, confirming lung specificity and prolonged antiviral activity. Conclusions: Extensive in vitro and in vivo evaluations demonstrate the LNP-mRNA-NbMS10 system's potential as a scalable, cost-effective, and adaptable alternative to current MERS-CoV therapies. This innovative platform offers a promising solution for preventing and treating respiratory infections, and countering emerging viral threats.

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