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Intramuscular delivery of mRNA-encoded single-chain variable fragments prevents myotoxin II-induced skeletal muscle damage in a preclinical model

Abstract:

Antivenom is the only effective treatment for snakebites, but it often fails to tackle venom-induced local tissue/muscle damage, leading to permanent disabilities. We investigated whether monoclonal single-chain variable fragments (scFvs) targeting myotoxin II (M-II) from Bothrops asper venom, delivered via mRNA-lipid nanoparticles (LNPs), could neutralise M-II-induced adverse effects under diverse settings. Human cultured myotubes transfected with mRNA-LNPs expressed scFvs within 24 h and showed resistance to both M-II and venom. In a mouse model, a single intramuscular injection of mRNA-LNPs prompted scFv expression within 48 h and protected against M-II-induced damage. This approach reduced biomarkers for muscle injury, myonecrosis, and damage to the basement membrane and vasculature. This study demonstrates the use of mRNA technology in snakebite management, serving as a proof of concept to improve treatments for envenomings. Although a prophylactic approach may not be feasible for snakebites, prompt delivery of antibodies at the bite site might improve patient outcomes.