Engineering Antivenom: Research Progress and Future Directions in Snakebite Envenoming Therapy.

Snakebite envenoming remains a major neglected tropical disease, causing substantial mortality and morbidity worldwide. While plasma-derived antivenoms have been the mainstay of treatment for over a century, they present important limitations related to safety, efficacy, specificity, scalability, and accessibility. Recent advances in biotechnology, venom and toxin characterization, and antibody engineering have enabled the development of new types of envenoming therapeutics, including recombinant antivenoms based on monoclonal antibodies and nanobody-based formats, as well as small-molecule inhibitors. These approaches are supported by advances in toxicovenomics, structural biology, and diagnostic technologies, which together facilitate a more rational, toxin-centric design paradigm. This review provides an overview of recent progress in the development of novel types of antivenom therapy, highlighting key design principles, emerging therapeutic modalities, and enabling technologies. Current challenges related to efficacy, breadth of coverage, manufacturability, and clinical translation are discussed, along with future perspectives for the development of safe, effective, and accessible treatments for snakebite envenoming.