A risk-based framework to guide oversight of nucleic acid constructs

Area of Science:

• Biosecurity
• Synthetic Biology
• Nucleic Acid Synthesis

Background:

• Current nucleic acid synthesis screening guidance lacks clarity, creating uncertainty for providers and policymakers regarding biosecurity oversight.
• This ambiguity can result in inadequate protection against high-risk products or unnecessary burdens on legitimate research for low-risk products.

Purpose of the Study:

• To present a risk-informed framework for classifying synthetic nucleic acid products based on biosecurity relevance.
• To inform proportionate screening guidance for synthetic nucleic acids.

Main Methods:

• Developed a three-tier classification system for synthetic nucleic acids based on input from synthetic biology and biosecurity specialists.
• Distinguished between custom and non-custom products, categorizing them into high-, intermediate-, and low-risk groups.

Main Results:

• Recommends strict scrutiny for longer DNA/RNA sequences (≥50 bp/nt), custom orders, and non-custom products from pandemic viruses or Federal Select Agent Program viruses.
• Suggests excluding very short oligonucleotides (<30 bp/nt) and non-DNA/RNA nucleic acids from routine screening.
• Identifies an intermediate-risk category for products requiring further investigation, including those incorporating nucleic acids into medical products and long viral sequences in non-custom repositories.

Conclusions:

• The proposed framework aims to align synthesis screening oversight with significant biological risks.
• Highlights evidence gaps and areas for future investigation in nucleic acid biosecurity.
• Provides a structured approach to manage biosecurity risks associated with synthetic nucleic acids.