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Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection.

Nat Commun.. 2018-10; 
Tiwari PM, Vanover D, Lindsay KE, Bawage SS, Kirschman JL, Bhosle S, Lifland AW, Zurla C, Santangelo PJ.
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摘要

The lung is a critical prophylaxis target for clinically important infectious agents, including human respiratory syncytial virus (RSV) and influenza. Here, we develop a modular, synthetic mRNA-based approach to express neutralizing antibodies directly in the lung via aerosol, to prevent RSV infections. First, we express palivizumab, which reduces RSV F copies by 90.8%. Second, we express engineered, membrane-anchored palivizumab, which prevents detectable infection in transfected cells, reducing in vitro titer and in vivo RSV F copies by 99.7% and 89.6%, respectively. Finally, we express an anchored or secreted high-affinity, anti-RSV F, camelid antibody (RSV aVHH and sVHH). We demonstrate that RSV aVHH, but n... More

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