Fc-free single-chain antibody mRNA therapy for airway infection of multidrug-resistant Pseudomonas aeruginosa

This study demonstrates that mRNA-based therapeutics encoding Fc-free single-chain variable fragment (scFv) antibodies can effectively treat infections caused by Pseudomonas aeruginosa by targeting its type III secretion system (T3SS), a key virulence mechanism; delivered via lipid nanoparticles, the mRNA enables sustained in vivo production of these small antibody fragments, which show superior penetration into lung tissue compared to larger antibody formats, resulting in reduced bacterial load, decreased lung inflammation, and improved survival in clinically relevant (including immunocompromised) models, thereby highlighting a promising, antibiotic-independent strategy to combat multidrug-resistant bacterial infections.