Snake venom gland organoids and biotechnological applications: a comprehensive review for translational medicine

Background Snake envenomation affects 1.2–5.5 million people annually, causing up to 125,000 deaths worldwide. This represents one of the most neglected tropical diseases globally. Traditional venom research relies on manual snake milking. This poses safety risks and produces variable venom quality. Current antivenom therapies suffer from species-specificity and batch-to-batch variation.Aim This review evaluates snake venom gland organoid technology as a transformative platform. The aim is to address critical limitations in venom research and antivenom production while exploring biotechnological applications.Experimental approach A narrative literature search was conducted across PubMed/MEDLINE, Web of Science, and Scopus databases (1990–2024). Systematic search strategies combined MeSH terms and keywords including "snake venom organoids" and "3D cell culture." Boolean operators were employed to combine search terms effectively. Inclusion criteria encompassed peer-reviewed English articles describing organoid technology applied to reptilian tissues. After removing duplicates and applying selection criteria, 67 directly relevant articles were analyzed. Additional references were identified through manual screening and citation tracking.Key findings Snake venom gland organoids have been successfully established from nine species across major venomous families. Organoids maintain cellular heterogeneity and authentic toxin production for over two years. They recapitulate native venom gland architecture and produce biologically active toxins. Genetic modification through CRISPR/Cas9 technology is possible. Applications span antivenom development, toxin production platforms, and drug discovery systems. Technology addresses traditional limitations while providing scalable pharmaceutical alternatives. Implementation timelines range 1–10 years across five biotechnological sectors.Conclusions Snake venom gland organoids represent a paradigm shift in toxinology research. They offer opportunities for standardized venom production and reduced animal dependence. Despite challenges in protocol standardization, this technology demonstrates significant commercial potential. Organoid platforms position as cornerstones for addressing global snakebite envenoming challenges.