Baker Lab: Neutralizing Snake Venom with AI-Designed Miniproteins

Researchers from the Baker Lab at the University of Washington, in collaboration with the Digital Biotechnology Lab at the Technical University of Denmark (DTU) and other institutions, have developed AI-designed proteins capable of neutralizing snake venom toxins.

Published in Nature, the study introduces computationally designed miniproteins that bind to and neutralize toxins from elapid snakes, including cobras and mambas. These venoms, which contain three-finger toxins, disrupt nerve-muscle communication, causing paralysis and cell death. Existing antivenoms, derived from animal plasma, are often expensive, difficult to produce, and ineffective against specific toxins.

The team used AI-powered protein design methods to create small, stable proteins that target key regions of these toxins. In laboratory tests, these proteins neutralized multiple toxin subtypes. Preclinical mouse studies demonstrated survival rates of 80-100% following exposure to lethal neurotoxins. According to co-senior author Tim Jenkins, the design process was significantly accelerated using software, eliminating the need for iterative experimental cycles and requiring only a few molecules to be tested.

These miniproteins offer several advantages over traditional antivenoms. They can be produced recombinantly without animal immunization, ensuring consistent quality. Their smaller size allows deeper tissue penetration, and their thermal stability supports easier transport and storage, particularly in regions without cold-chain infrastructure. Additionally, the proteins showed no adverse side effects in animal models, a critical step toward their potential clinical application.

The study highlights how computational protein design can address global health challenges, particularly in resource-limited settings. David Baker, director of the Institute for Protein Design, noted, “By lowering costs and resource requirements for protein-based medicines, we’re taking considerable steps toward a future where everyone can get the treatments they deserve.”

The project also involved collaborators from institutions such as the Liverpool School of Tropical Medicine, University of Liverpool, MIT, and others. While traditional antivenoms remain essential, these AI-designed antitoxins could enhance or supplement existing therapies and have potential applications in treating other conditions, including viral infections and autoimmune diseases.

This work was supported by several funding organizations, including the Open Philanthropy Project, Novo Nordisk Foundation, and the European Union’s Horizon 2020 program.

Cover image: Baker Lab

Topics: AI & Digital