Strengthening nucleic acid biosecurity screening against generative protein design tools
Advances in artificial intelligence (AI)-assisted protein engineering are enabling breakthroughs in the life sciences but also introduce new biosecurity challenges. Synthesis of nucleic acids is a choke point in AI-assisted protein engineering pipelines. Thus, an important focus for efforts to enhance biosecurity given AI-enabled capabilities is bolstering methods used by nucleic acid synthesis providers to screen orders. We evaluated the ability of open-source AI-powered protein design software to create variants of proteins of concern that could evade detection by the biosecurity screening tools used by nucleic acid synthesis providers, identifying a vulnerability where AI-redesigned sequences could not be detected reliably by current tools. In response, we developed and deployed patches, greatly improving detection rates of synthetic homologs more likely to retain wild type-like function.
Authors
- Jacob Beal (ORCID: https://orcid.org/0000-0002-1663-5102)
- Tessa Alexanian (ORCID: https://orcid.org/0000-0003-1108-7124)
- James Diggans (ORCID: https://orcid.org/0000-0003-3871-2380)
- Bryan T. Gemler (ORCID: https://orcid.org/0000-0002-9635-4545)
- Eric Horvitz (ORCID: https://orcid.org/0000-0002-8823-0614)
- Nicole E. Wheeler (ORCID: https://orcid.org/0000-0003-4599-9164)
- Steven T. Murphy (ORCID: https://orcid.org/0009-0009-6072-1655)
- Bruce J. Wittmann (ORCID: https://orcid.org/0000-0001-8144-9157)
- Tom Mitchell (ORCID: https://orcid.org/0000-0002-7636-5597)
- Adam Clore (ORCID: https://orcid.org/0000-0002-0930-1497)
- Craig Bartling (ORCID: https://orcid.org/0000-0002-3040-7149)
- Kevin Flyangolts (ORCID: https://orcid.org/0009-0000-5232-9615)
Institutions
- Microsoft (United States) (US)
- Association for Computing Machinery (US)
- Battelle (US)
- International Baccalaureate (CH)
- Biology of Infection (FR)
- Twist Bioscience (United States) (US)
- Integrated DNA Technologies (United States) (US)
Publication Details
- Journal
- Science
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1126/science.adu8578
- Citations
- 15
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 25.74