About This Project

Snakebite envenoming causes over 100,000 deaths annually, yet current antivenoms depend on animal plasma. Adam & Snakes develops synthetic single-domain antibodies (sdAbs, nanobodies) as stable, ethical, and scalable alternatives. Using in vitro display, affinity screening, and neutralization assays, we will assess sdAb potency and breadth against Bothrops and Naja venoms to match or surpass existing sera.

Ask the Scientists

What is the context of this research?

Snakebite envenoming is a neglected tropical disease causing over 100,000 deaths annually, mainly in tropical and rural regions (WHO 2023). Current antivenoms are derived from hyper-immunized animal plasma, a century-old process that is slow, variable, and often ineffective against local snake species (Gutiérrez et al., Nat Rev Drug Discov 2017). Advances in in vitro display technologies now enable the generation of fully synthetic single-domain antibodies (sdAbs) that combine high thermal stability with low manufacturing cost (Muyldermans 2013, Annu Rev Biochem). This project tests the hypothesis that sdAbs selected from synthetic libraries can bind and neutralize major Bothrops and Naja toxins with potency comparable to animal-derived antibodies. Demonstrating this proof-of-concept would establish a scalable, cruelty-free framework for next-generation antivenoms. This idea has been proposed for non Brazilian snakes (Ahmadi et al., Nature 2025, Benard-Valle et al. Nat Comm 2024).

What is the significance of this project?

This project will generate the first experimental evidence that fully synthetic single-domain antibodies (sdAbs) can neutralize snake venom toxins without animal immunization. While synthetic antibody libraries have been applied to infectious diseases and oncology, their use for antivenoms has never been validated experimentally. Demonstrating that in vitro–selected sdAbs bind and neutralize Bothrops and Naja toxins will provide essential proof that a recombinant, cruelty-free discovery pipeline can replace animal plasma–derived antibodies. These data will inform the design of optimized sdAb scaffolds and expression workflows, guiding future translational programs toward region-specific, rapidly deployable antivenoms. By linking synthetic antibody engineering directly to global health needs, this work will bridge a critical scientific and ethical gap in venom therapeutics.

What are the goals of the project?

This project aims to demonstrate a proof of concept for a fully synthetic, cruelty-free antivenom targeting snakes endemic to Brazil. We will screen synthetic single-domain antibody (sdAb) libraries against crude venoms from Bothrops jararaca and Bothrops atrox—species responsible for most Brazilian envenomations.

The first goal is to identify at least ten high-affinity single-domain antibody (sdAb) binders using in vitro display selection.

The second goal is to express and purify these binders in E. coli and assess their stability and binding activity using ELISA and neutralization assays.

The third goal is to formulate an optimized sdAb mixture that matches or exceeds the potency of reference animal-derived plasma.

Successful validation will enable technology transfer to Fiocruz Manguinhos for pilot-scale manufacturing and regional deployment