Intramuscular delivery of mRNA-encoded single-chain variable fragments prevents myotoxin II-induced skeletal muscle damage in a preclinical model
Almeida, J. R., Sørensen, C. V., Gilabadi, S., Williams, J., Haidar, H. B., Møiniche, M. v. B., Benard-Valle, M., Rivera-de-Torre, E., Schultz, D., Urquhart, A., Lomonte, B., Patel, K., Laustsen, A. H. and Vaiyapuri, S.
It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing. Abstract/SummaryAntivenom 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 scFvs targeting myotoxin II (M-II) from Bothrops asper venom, delivered via messenger ribonucleic acid-lipid nanoparticle (mRNA-LNP), could neutralise M-II under diverse settings. Human cultured myotubes transfected with mRNA-LNPs encoded scFvs within 24 hours and showed resistance to M-II and venom. In a mouse model, a single intramuscular injection of mRNA-LNPs prompted scFv expression within 48 hours 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 represents the first demonstration of 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 may significantly improve patient outcomes.
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