NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules

Last Updated: July 24, 2024 9:30:31 AM PDT

Learn about the NIH safety practices and containment procedures for research and clinical trials involving recombinant or synthetic nucleic acid molecules.

All UC San Diego researchers working with recombinant or synthetic nucleic acid molecules must follow the National Institute of Health (NIH) Guidelines on Research Involving Recombinant DNA Molecules. Compliance with the NIH Guidelines is mandatory and it is the responsibility of each investigator to make sure that their laboratory is in compliance. The following outline is intended only to serve as an outline to the NIH Experiment Guidelines:

Experiments that require NIH and IBC approval prior to initiation (Section III-A, B & C)
Experiments that require IBC approval prior to initiation (Section III-D)
Experiments that require registration simultaneous with initiation (Section III-E)
Experiments that are exempt; but still may require registration (Section III-F)

Guideline of Research Activities and their corresponding minimum Biosafety Level and applicable section, per the National Institute of Health (NIH)
Activity	Minimum BSL	Section
Experiments that require IBC Approval, RAC Review and NIH Director Approval before Initiation (III-A)
Transfer of a drug resistance trait to microorganisms compromising ability to control disease agents in humans, veterinary medicine or agriculture.	Varies*	III-A-1-a
Experiments that Require NIH/OBA and IBC Approval before Initiation (III-B)
Cloning of toxin molecules with LD50 of less than 100 nanograms per kilogram body weight	Varies*	III-B-1
Experiments that Require IBC and Institutional Review Board Approvals and RAC Review before Research Participant Enrollment (III-C)
Transfer human gene into human research participant(s) using recombinant or synthetic nucleic acid molecules or DNA or RNA	Varies*	III-C-1
Experiments that Require IBC Approval Before Initiation (III-D)
Adding nucleic acids to agents to RG2	2	III-D-1-a
Adding nucleic acids to agents to RG3	3	III-D-1-b
Adding nucleic acids to agents to RG4	4	III-D-1-c
Adding nucleic acids to restricted agents	4	III-D-1-d
Adding nucleic acids from agents into nonpathogenic prokaryotes or lower eukaryotes	BSL1 or higher	III-D-2
Nucleic acids in viral vectors RG2	2	III-D-3-a
Nucleic acids in viral vectors RG3	3	III-D-3-b
Nucleic acids in viral vectors RG4	4	III-D-3-c
Nucleic acids in viral vectors, such as restricted poxviruses	Varies*	III-D-3-d
Creation, breeding, transfer and experimentation with transgenic and knockout animals.	See matrix of activities (PDF)	See matrix of activities (PDF)
Nucleic acid-modified microorganisms tested on whole animals	BSL1 or higher	III-D-4
Generation of transgenic plants or testing of nucleic acid-modified microorganisms or insects on whole plants at BSL2P+ or higher	BSL2P+ or higher	III-D-5
Large-scale experiments greater than 10 liters of culture	BSL1 or higher	III-D-6
Influenza virus experimentation: H2N2 (1957-1968)	3 Enhanced	III-D-7
Influenza virus experiments: Highly Pathogenic Avian (H5N1)¹	BSL2+ or higher	III-D-7-b
Influenza virus experiments: 1918 H1N11^1,2	BSL3	III-D-7-c
Experiments involving gene drive modified organisms generated by recombinant or synthetic nucleic acid molecules	BSL2 or higher, ABSL2 or higher, BSL2P+ or higher	III-D-8
Experiments that require IBC notice simultaneous with initiation (III-E)
Use of viral vectors (<2/3 viral genome) in tissue culture	BSL1 or 2	III-E-1
Generation of transgenic plants or testing of nucleic acid-modified microorganisms or insects on whole plants at BSL1P+ or BSL2P	BSL1P or 2P	III-E-2
Generation of transgenic rodents (BSL1 only)	1	III-E-3
Exempt experiments (III-F)
Synthetic nucleic acids that cannot replicate nor integrate on a living cell (i.e. oligos)	Varies	III-F-1
Nucleic acids that are not in organisms, cells or viruses	Varies	III-F-2
Exact nucleic acid sequence from a single source that exists contemporaneously in nature	Varies	III-F-3
Prokaryotic host plasmids or viruses used only in that host or closely related strain	Varies	III-F-4
Eukaryotic host nucleic acids used only in that host or closely related strain	Varies	III-F-5
Nucleic acids entirely of DNA segments from different species that exchange DNA by known physiological processes	Varies	III-F-6
Genomic DNA molecules that have acquired a transposable element	Varies	III-F-7
Nucleic acids that do not present a significant risk to health or the environment (See Appendix C, Exemptions under Section III-F-8 for other classes of experiments which are exempt from the NIH Guidelines. ) Refer to Escherichia coli Strains and NIH Guidelines for more information.	Varies	III-F-8
Requires review by NIH ¹ Dual Use Research of Concern regulations apply* ² Select Agent regulations apply

If you are unsure in which category your experiments fall, contact the EH&S Biosafety team for assistance.

General Responsibilities of the PI

Fully comply with the NIH Guidelines on the conduct of recombinant or synthetic nucleic acid molecule research.
Obtain Institutional Biosafety Committee (IBC) approval of an initial research protocol prior to initiating any research with recombinant or synthetic nucleic acid molecules or infectious agents, by way of a Biohazard Use Authorization (BUA).
Remain in communication with the IBC and Biosafety Officer throughout the conduct of the research. Any changes resulting in an increased level of hazard, addition of new biological materials, new procedures or change in locations, requires a BUA amendment and IBC approval prior to commencing work.
Adhere to approved containment and emergency plans for handling accidental spills and personnel exposure. Report any significant problems, violations of the NIH Guidelines, or any significant research-related accidents and illnesses to the Biological Safety Officer.
Be adequately trained in good microbiological techniques and use appropriate microbiological practices and laboratory techniques for the research being performed.
Ensure the integrity of the physical containment (e.g., biological safety cabinets) and the biological containment (e.g., purity and genotypic and phenotypic characteristics). Investigate and report any significant problems pertaining to the operation and implementation of containment practices and procedures in writing to the Biological Safety Officer.
Comply with shipping requirements for recombinant or synthetic nucleic acid molecules.
Make available to all laboratory staff the protocols that describe the potential biohazards and the precautions to be taken.
Ensure that laboratory personnel receive appropriate training regarding their duties, the practices and techniques required to ensure safety, and the necessary precautions to prevent exposures and deal with accidents. Supervise the safety performance of the laboratory staff to ensure that the required safety practices and techniques are employed. Correct work errors and conditions that may result in the release of recombinant or synthetic nucleic acid molecule materials or infectious agents.

References

Contact EH&S Biosafety.