5. Class III-E experiments

Class III-E experiments require IBC notification and submission of an rDNA Registration Document simultaneously with initiation. Those experiments not included under Classes A, B, C, D or F are considered in this class. For example, experiments in which all components are derived from non-pathogenic prokaryotes and non-pathogenic lower eukaryotes are included in this class and can be carried out at BSL1 containment. Creation of transgenic and knockout animals, or other projects which involve modification of the genome, that may be housed at ABSL1 containment, are also classified under III-E. Additional rsNAM experiments include:

  1. Experiments involving the formation of rsNAM containing no more than two-thirds of the genome of any eukaryotic virus (all viruses from a single Family being considered identical). These experiments may be propagated and maintained in cells in tissue culture using BSL1 containment. For such experiments, it must be demonstrated that the cells lack helper virus for the specific Families of defective viruses being used. If helper virus is present, procedures specified under Section III-D-3 should be used. The DNA may contain fragments of the genome of viruses from more than one Family but each fragment shall be less than two-thirds of a genome.
  2. Experiments involving nucleic acid molecule-modified whole plants, and/or nucleic acid molecule-modified organisms associated with whole plants, except those that fall under Section III-A, III-B, III-D, or III-F. It should be emphasized that knowledge of the organisms and judgment based on accepted scientific practices should be used in all cases in selecting the appropriate level of containment. By contrast, a lower level of containment may be appropriate for small animals associated with many types of rsNAM-modified plants.
  • BSL1-P is recommended for all experiments with rsNAM-containing plants and plant-associated microorganisms not covered in Section III-E-2-b or other sections of the NIH Guidelines.
  • BSL2-P or BSL1-P+ biological containment is recommended for the following experiments:
    • Plants modified by rsNAM that are noxious weeds or can interbreed with noxious weeds in the immediate geographic area.
    • Plants in which the introduced DNA represents the complete genome of a non-exotic infectious agent.
    • Plants associated with rsNAM-modified non-exotic microorganisms that have a recognized potential for serious detrimental impact on managed or natural ecosystems.
    • Plants associated with rsNAM-modified exotic microorganisms that have no recognized potential for serious detrimental impact on managed or natural ecosystems.
    • Experiments with rsNAM-modified arthropods or small animals associated with plants or with arthropods or small animals with rsNAM-modified microorganisms associated with them if the rsNAM-modified microorganisms have no recognized potential for serious detrimental impact on managed or natural ecosystems.
  1. Experiments involving the generation of rodents in which the animal's genome has been altered by stable introduction of rsNAM, or DNA derived therefrom, into the germ-line (transgenic rodents Only experiments that require BSL1 containment are covered under this section; experiments that require BSL2, BSL3, or BSL4 containment are covered under Section III-D-4.
  • Breeding transgenic/knockout rodents that may be housed under ABSL1 containment conditions are exempt, with the exception of:
    • Breeding experiments involving transgenic rodents that contain more than 50 percent of the genome of an exogenous eukaryotic virus from a single family, in order to prevent inadvertent reconstitution of an exogenous virus in the resultant transgenic rodent; and
    • Breeding experiments in which the transgenic rodent's transgene is under the control of a gammaretroviral long terminal repeat (LTR), in order to address the small risk of recombination with endogenous retroviruses which could potentially result in mobilization of the transgene via a replication-competent mouse retrovirus.
    • Cross-breeding of the exempt transgenic/knockout rodents housed under ABSL1 containment conditions do not have to be registered with the IBC for approval.