Defending Synthetic DNA Orders Against Splitting-Based Obfuscation

Biosecurity screening of synthetic DNA orders is a key defense against malicious actors and careless enthusiasts producing dangerous pathogens or toxins. It is important to evaluate biosecurity screening tools for potential vulnerabilities and to work responsibly with providers to ensure that vulnerabilities can be patched before being publicly disclosed. Here, we consider a class of potential vulnerabilities in which a DNA sequence is obfuscated by splitting it into two or more fragments that can be readily joined via routine biological mechanisms such as restriction enzyme digestion or splicing. We evaluated this potential vulnerability by developing a test set of obfuscated sequences based on controlled venoms, sharing these materials with the biosecurity screening community, and collecting test results from open source and commercial biosecurity screening tools, as well as a novel Gene Edit Distance algorithm specifically designed to be robust against splitting-based obfuscations.