The Case for Limiting "Sequences of Concern" to Those with Demonstrated Pathogenic Function.

Area of Science:

• Biosecurity
• Synthetic Biology
• Bioinformatics

Background:

• Screening synthetic nucleic acid orders is vital for biosecurity but incurs costs for providers.
• Current screening relies heavily on taxonomy, particularly for viral sequences.
• The debate continues on which sequence functions constitute a biosecurity concern.

Purpose of the Study:

• To evaluate the role of sequence function, beyond taxonomy, in biosecurity screening.
• To propose a framework for assessing the concern level of nonviral synthetic nucleic acid sequences.
• To differentiate between sequences with known concerning functions and those with unknown or hypothetical functions.

Main Methods:

• Analysis of existing biosecurity screening protocols for synthetic nucleic acids.
• Review of scientific literature to identify functions of concern.
• Comparative analysis of viral and nonviral sequence screening criteria.

Main Results:

• Taxonomy remains crucial, but sequence function is increasingly important for determining concern levels.
• Nonviral sequences with unknown or hypothetical functions should not be considered of concern by default.
• A sequence must have a documented concerning function in published literature to be classified as a nonviral sequence of concern.

Conclusions:

• Future biosecurity screening must integrate functional analysis with taxonomic identification.
• A clear definition of 'concerning functions' is needed for consistent screening.
• The proposed approach balances biosecurity needs with the operational realities of nucleic acid providers.