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An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions

Cell Rep Med. 2023-11; 
Cailin E Deal, Angelene F Richards, Tracy Yeung, Max J Maron, Ziqiu Wang, Yen-Ting Lai, Brian R Fritz, Sunny Himansu, Elisabeth Narayanan, Ding Liu, Rositsa Koleva, Stuart Licht, Chiaowen J Hsiao, Ivana L Rajlic, Hillary Koch, Michael Kleyman, Mark E Pulse, William J Weiss, Jennifer E Doering, Samantha K Lindberg, Nicholas J Mantis, Andrea Carfi, Obadiah J Plante
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Proteins, Expression, Isolation and Analysis … nanoparticles (LNPs) that express glycosylated, dimeric IgA with … The same mRNA-LNP technology was used to express a … Sal4 IgG (Genscript) was purified from transient transfection … Get A Quote

摘要

Colonization of the gut and airways by pathogenic bacteria can lead to local tissue destruction and life-threatening systemic infections, especially in immunologically compromised individuals. Here, we describe an mRNA-based platform enabling delivery of pathogen-specific immunoglobulin A (IgA) monoclonal antibodies into mucosal secretions. The platform consists of synthetic mRNA encoding IgA heavy, light, and joining (J) chains, packaged in lipid nanoparticles (LNPs) that express glycosylated, dimeric IgA with functional activity in vitro and in vivo. Importantly, mRNA-derived IgA had a significantly greater serum half-life and a more native glycosylation profile in mice than did a recombinantly produced IgA... More

关键词

IgA, Pseudomonas, Salmonella, antibody, dimeric, infection, mRNA, mucosal, therapy
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