Defending synthetic DNA orders against intra-order 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. We consider a class of potential vulnerabilities in which a DNA sequence is obfuscated by splitting it into two or more fragments within a single synthetic DNA order, where the fragments can be readily reassembled via routine biological mechanisms. To evaluate this potential vulnerability, we develop a test set of obfuscated sequences based on controlled toxins, and share these materials with the biosecurity screening community. We then collect and analyze results from open-source and commercial biosecurity screening tools, alongside a novel Gene Edit Distance algorithm specifically designed to be robust against splitting-based obfuscations. Biosecurity screening of synthetic DNA orders is a key defense against production of dangerous pathogens or toxins. Here the authors test the Gene Edit Distance algorithm that identifies the obfuscated DNA regardless of the fragment lengths.