Guidance on the Regulation of Select Agent & Toxin Nucleic Acids
Under the current select agent regulations the following are examples of materials that would not be regulated as a select agent.
- Nucleic acids or genetic elements that cannot produce infectious forms of any of the regulated select agent viruses. These include:
- Nucleic acids encoding complete genomes of single-stranded negative strand RNA viruses,
- Double stranded RNA viruses, and
- Double-stranded DNA viruses that require a unique polymerase (Variola virus*, monkeypox virus [except West African clade], African swine fever virus, goat pox virus, Lumpy skin disease virus, and sheep pox virus).
- PCR products and primers or DNA fragments of select agents or toxins (unless they encode for a toxic form of a select toxin and can be expressed).
- Complementary DNA made from regulated select agent nucleic acids (only the positive strand RNA form of the viral genome is regulated). Complementary DNA copies of select agent viral genomes, including reverse genetics systems, are not regulated because they would first need to be transcribed into RNA, then translated into protein, and therefore would not be an immediate precursor to the virus.
- Nucleic acids that encode for the genomes of select agent bacteria or fungi, including chromosomal, recombinant, or synthetic DNA.
- Nucleic acids that encode for toxins not subject to the select agent regulations but derived from regulated select agents.
- Nucleic acids that encode for toxins and the genomes of select agents that have been excluded from regulation under section 3(e) of the select agent regulations. Please see the FSAP website for a list of excluded select agents. If the entity possesses an attenuated strain that is not included in the list of excluded agents, the entity can request that the strain be excluded. Please see the Exclusions Guidance Document for additional information on how to request exclusion.
- Select agent nucleic acid sequence information.
*With the exception of activities conducted by or under the authority of the HHS Secretary, under federal criminal law it is unlawful for any person to knowingly produce, engineer, synthesize, acquire, transfer directly or indirectly, receive, possess, import, export, or use, or possess and threaten to use, variola virus. See 18 U.S.C. § 175c. For purposes of 18 U.S.C. § 175c, “variola virus” is defined as “a virus that can cause human smallpox or any derivative of the variola major virus that contains more than 85 percent of the gene sequence of the variola major or the variola minor virus.”