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. ORCID: https://orcid.org/0000-0002-6006-6517 (2025) Intramuscular delivery of mRNA-encoded single-chain variable fragments prevents myotoxin II-induced skeletal muscle damage in a preclinical model. Trends in Biotechnology. ISSN 1879-3096 doi: 10.1016/j.tibtech.2025.10.017 (In Press)

Abstract/Summary

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 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.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/125496
Identification Number/DOI	10.1016/j.tibtech.2025.10.017
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Cell Press
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