Enhancing Gene Synthesis Security: An Updated Framework for Synthetic Nucleic Acid Screening and the Responsible Use of Synthetic Biological Materials.

Introduction: In response to continuous advancements in synthetic biotechnologies and in the availability of synthetic nucleic acids to the biological research community since the publication of the 2010 HHS synthetic double-stranded DNA (dsDNA) screening framework, the U.S. government undertook a comprehensive and stakeholder-driven review and revision process. This culminated in the publication of a new screening framework for synthetic nucleic acids in October 2023, followed by an Executive Order directing departments and agencies of the U.S. government to take certain measures in support of implementing the screening framework. This review provides an overview of the process by which stakeholder comments were considered and by which the 2023 screening framework was drafted. A summary of expected impacts on the life sciences research community is also provided.

Methods: Comments were solicited from synthetic biology stakeholders through the publication of two Notices, in 2020 and 2022. The 2020 Notice elicited 15 unique responses totaling 220 pages, and the 2022 Notice elicited 26 unique responses totaling 79 pages. These were considered by a deliberative interagency group, resulting in a revised screening framework in 2023.

Discussion And Conclusion: The adoption of the 2023 screening framework, and related provisions in the Executive Order that followed, will impact researchers and biosafety officers across the U.S. bioeconomy. For instance, this screening framework is no longer limited in its recommendations to providers of synthetic dsDNA containing sequences unique to regulated pathogens or toxins, but now includes recommendations to all entities involved in the sale, use, and transfer of all forms of synthetic nucleic acids encoding genetic sequences that contribute to pathogenicity or toxicity-whether from regulated agents or not. Biosafety professionals are emerging as a critical resource for establishing and fostering a culture of biosecurity surrounding synthetic nucleic acids containing these high consequence genetic sequences.

Significance: The work presented is significant because the scope of the 2010 screening framework has been expanded to include roles and responsibilities for new entities across the life sciences research landscape. This will likely impact biosafety professionals, who may be well positioned in their institutions to coordinate these new responsibilities.