The Joint Genome Institute's Synthetic Biology Biosecurity DNA Screening Process

Concerns have been raised that individuals with malicious intent could exploit DNA synthesis technology in order to obtain genetic elements from organisms and toxins that would otherwise be difficult to obtain. In response to these concerns, the U.S. Department of Health and Human Services issued the Screening Framework Guidance for Providers of Synthetic Double-Stranded DNA. The voluntary Guidance outlines the U.S. government’s recommendations for screening double-stranded DNA to ensure that existing regulations[1] are followed, encourage best practices in addressing biosecurity concerns, and reduce the risk that individuals with ill intent may exploit the application of nucleic acid synthesis technology to obtain genetic material derived from or encoding Select Agents or Toxins, or agents on the EAR’s Commerce Control List (CCL).

In accordance with the Guidance, the U.S. Department of Energy Joint Genome Institute has developed a DNA screening pipeline to screen all sequences that are synthesized through it’s synthetic biology program. The screening method detects “sequences of concern” of at least 200 nucleotides in length on either DNA strand, and the resultant polypeptides from translations using the three alternative reading frames on each DNA strand (or six-frame translation).  Sequences are aligned to the sequences in GenBank’s nucleotide and protein databases rather than a curated database, to ensure that it automatically adapts as new sequences are added to GenBank.  A “Best Match” approach is used to determine whether a query sequence is unique to Select Agents or Toxins, or CCL-listed agents, toxins or genetic elements, and to minimize false positives from closely related organisms or highly conserved “house-keeping genes” which do not pose a biosecurity threat.