Minimal Risk Application Guidelines

Please consider the following guidelines when completing applications that involve the use of GM rodents, recombinant K-12 E. coli, or pre-generated genetically modified cells. Applications that only involve these types of activities are considered minimal risk and NIH exempt (III-F). Please be aware that while these experiments are considered exempt from the NIH Guidelines, they are still under IBC oversight and require an application. These applications are typically reviewed outside of the IBC meeting cycle.

GM Rodents

To account for the use of other purchased, provided, or already made genetically engineered or genetically modified rodents for breeding purposes or for general use:

  1. Select the box for Genetic Modification of Animals in the Activities Include section.
  2. In the Study Objectives section 1b, 
    1. Describe the work with the GM rodents. If cells or tissues are collected from the mice, please indicate so.
    2. If true, please write that the transgenic rodents do not contain the following genetic modifications: (i) incorporation of more than one-half of the genome of an exogenous eukaryotic virus from a single family of viruses; or (ii) incorporation of a transgene that is under the control of a gammaretroviral long terminal repeat (LTR).
    3. If you will breed GM/GE rodents and if it is also true, please state that all transgenic rodents resulting from breeding are not expected to contain more than one-half of an exogenous viral genome from a single family of viruses.
  3. Complete the Genetic Modification of Animals section 6.
    1. Responding “yes” to 6)a allows for the use of boxes 6a)i and 6a)ii to describe the GM rodents.
    2. To account for only the use of existing GM rodents in your application, check “yes” for question 6)a and include in the 6a)i text box- “EXISTING GM rodents-FOR USE ONLY.” 
    3. In the text box for 6a)ii enter a general description of the modified phenotypes and briefly describe the genetic modifications, making clear what genes are produced or impacted (knocked out), and describe any risks (if any) from these modifications. The IBC admin may contact you for any clarifications. 
    4. Include the IACUC protocol ID in section 6a)i for applicable species (vertebrates).  
  4. Complete Safety section 7 and enter a lab location and animal housing location in Safety section 7a)i.
    1. Note: the Animal Housing Location under Safety section 7a)ii only becomes active if other sections of the application indicate that administration of r/sNA, infectious agents, or biologically-derived toxins occurs with animals.
  5. In the Attachments section,
    1. Include a Biological Decontamination and Spill Clean-up Plan.
    2. Include a Biological Waste Disposal Plan.
    3. Include an SOP if experimental activities (other than breeding) are performed. Describe all handling or use of GM rodents, their containment, and PPE requirements. The level of detail included should provide enough information to assist the IBC in its risk assessment.

Pre-generated Genetically Modified Cells

Experiments which involve the use of pre-made genetically engineered cells should be accounted for by including a gene transfer method in the Gene Transfer Table 2a, even though the agent is already recombinant and r/sNA molecules are not being transferred.

To account for the use of other purchased, provided, or already made genetically engineered cells:

  1. Select the box for “recombinant or synthetic nucleic acid molecules” in the “Activities Include” section.
  2. Complete the “Study Objectives” section (1) a and b, with a brief description and the goals/aims of the work involving the pre-engineered cells.
  3. In the “Recombinant/Synthetic Nucleic Acid Molecules (r/sNA Mol)” section (2): Include a gene transfer method in Table 2a. Select an “other” method of transfer and in the pop-up window:
    1. In section a) name the GM cells. 
    2. In section b), indicate if the cells will be administered to whole vertebrate animals. If so, complete the associated follow-up questions.
    3. In section c), briefly describe the GM cells and source. 
    4. In section d), provide the scientific rationale for using the GM cells in your study. Relevant publications describing the GM cells could be referenced. You will need to enter something brief in this section in order to fulfill an application dependency.
  4. Include (as best you can for the risk assessment) the genetic material that the engineered cells express or have altered in the Genetic Material to be Transferred Table 2b. 
  5.  In the “Safety” section (7) include: The laboratory location where this work will be performed and where the GM cells are stored with the proposed BSL in section 7a)i. Fill in sections b through h accordingly.
  6. Under i) Laboratory Procedures, add the experimental activity and appropriate SOP title for the work with the pre-made cells.
  7. In the “Attachments” section attach: 
    1. Biological Decontamination and Spill Clean-up Plan (tailor to your lab and application)
    2. Biological Waste Disposal Plan (tailor to your lab and application)
    3. Corresponding vector maps. Note: An attachment must be included as a vector map if r/sNA work is indicated in the application. If there is no vector map, please attach a document that states, “no vector map for pre-made agent.” Or consider attaching a product data sheet or reference that corresponds to the pre-made cells.
    4. SOPs for the use and handling of the pre-made cells.

Transformations of K-12 Strains of E. coli or Use of Recombinant K-12 Strains of E. coli

Although exempt from NIH Guidelines (III-F), transforming E. coli K-12 strains or culturing recombinant K-12 E. coli must be approved by the IBC. Recombinant protein expression typically uses E.coli that is not K-12 and is not exempt from the NIH Guidelines. Use of risk group 3 or 4 genes/sequences, or sequences that produce toxins require a full IBC review.

To add the transformation of E. coli (K-12 strains) or the culturing of recombinant K-12 strains to an IBC application:

  1. In the “Activities Include” section, select “Recombinant or Synthetic Nucleic Acid Molecules.” 
  2. Complete the “Study Objectives” section (1) a and b, with a brief description, goals/aims of this exempt work.
  3. In the “Recombinant/Synthetic Nucleic Acid Molecules (r/sNA Mol)” section (2):
    1. Add a gene transfer method (chemical/physical) and fill in the corresponding pop-out window. Some methods typically used are heat-shock or electroporation of chemically competent E. coli. Include the strain of E. coli used in the description section (a) of the pop-out window (non-K-12 strains are not exempt).
    2. List, as separate line items, all r/sNA molecules (genes/sequences) under “Genetic Material to be Transferred” (b). (typically not the backbone vector genes/sequences unless they will be expressed in eukaryotes)
  4. In the “Safety” section (7) include: 
    1. The laboratory where this work will be performed (a-i).
    2. Fill in b through h accordingly.
    3. Under i) Laboratory Procedures, add the experimental activity and appropriate SOP title.
  5. In the “Attachments” section attach: 
    1. Biological Decontamination and Spill Clean-up Plan (tailor to your lab and application)
    2. Biological Waste Disposal Plan (tailor to your lab and application)
    3. Attach (no modification required) the SOP “Biosafety Practices for the Transformation of exempt E. coli K-12 strains and/or Use of Recombinant E. coli K-12 strains”