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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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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