Regulatory Interpretation

Date: February 7, 2017

Subject: Regulatory Interpretation regarding synthetically created DNA sequence

This response addresses your January 3, 2017 request for a regulatory interpretation of whether synthetically created DNA sequences would be considered a select agent or toxin as defined by sections 3(c)(3) and 4 (c)(3) of the select agent regulations, which specifically states that “…select agents and toxins that have been genetically modified” are select agents and toxins.  Sections 3(c)(3) and 4 (c)(3) apply to genetically modified select agents and toxins, but not DNA, whether from the natural source or synthetically derived.

The following synthetically created DNA would be regulated:  

  • Nucleic acids that can produce infectious forms of any of the select agent viruses.
  • Recombinant and/or synthetic nucleic acids that encode for the functional form(s) of select toxins if the nucleic acids:
    • Can be expressed in vivo or in vitro, or
    • Are in a vector or recombinant host genome and can be expressed in vivo or in vitro.

Please note that if unregulated synthetically modified DNA sequences are used to derive a select agent or toxin the resulting agent will be regulated. 

The Federal Select Agent Program (FSAP) guidance document titled Guidance on the Regulation of Select Agent and Toxin Nucleic Acids addresses genetically modified select agents and toxins: “Depending upon the extent of the modification genetically modified select agents or toxins may be regulated.

Genetic modifications include but are not limited to deletion mutants, insertion mutants, point mutants, and chimeric select agents.  If the genetic modification renders the select agent or toxin attenuated or less potent or toxic then the select agent or toxin may be excluded.”  This Guidance also provides a list of the nucleic acids that are regulated as well as those nucleic acids that are not regulated. Please see our Exclusions Guidance Document for examples of material that is excluded from the regulations.