Instructions for synthetic nucleic acid molecule, rDNA and infectious agent/toxin questions on the ePPQ:
- If you are submitting a grant renewal or a new project where the rDNA, synthetic nucleic acid molecule, infectious agent, or biological toxin work is IDENTICAL to a previously approved IBC project, fill in the IBC # on the form. Depending on the date of your last approval, you may need to complete the annual renewal form for this project. You must have an approval by the IBC within the past 12 months in order to have grant funds set-up into your account.
- If the rDNA, synthetic nucleic acid molecule, infectious agent, or biological toxin work is nearly identical but some modifications are needed (e.g., new gene inserts), you may still include your approved IBC #. Check the revision policy to see if your modification needs advanced approval, or contact the IBC if you are unsure.
For rDNA work that was previously determined to be exempt:
- If you are submitting a non-competing renewal and are not adding any new rDNA work that may not be exempt (e.g., in vivo work or using a viral vector), you may check the box that indicates the project is exempt.
- If you are submitting a new or competing grant, you must also submit the Initial Classification form to get a new exempt determination by the IBC.
For new rDNA or Infectious agent work:
- Submit either the Initial rDNA Research Classification form and/or Infectious Agent Questionnaire as appropriate
- If you are unsure whether this work can be included under a previous IBC # or not, contact the IBC.
Determination of exemption for synthetic nucleic acid molecule work:
- The synthetic nucleic acid molecule question in the PPQ will provide the initial screening for determining if the work in the grant is exempt from IBC review. Depending upon how the question is answered, you may also need to submit the Initial Classification form for a determination of exemption.
- If a grant has previously been determined to be exempt and you are submitting a non-competing renewal for that grant and are not adding any new synthetic nucleic acid work that may not be exempt (see FAQ below), you may check the box that indicates the project has been previously determined to be exempt.
Guide to Forms and Usage:
Initial Classification form:This form must be submitted for all new grant/contract submissions when recombinant DNA work is included in project, unless the work can be included under a previously approved IBC project and for synthetic nucleic acid research that is not determined to be exempt within the ePPQ. See above FAQ
Recombinant DNA Research Questionnaire (RDRQ):
- This form must be included for new non-exempt recombinant DNA research. This includes work with virally-based vectors, recombinantly modified infectious agents, or any in vivo use of recombinant DNA (with the exception of transgenic animals created by a core facility or outside your lab)
- The Initial Classification form should precede this form. The IBC will inform you if an RDRQ is needed.
Infectious Agent /Toxin Questionnaire:
- This form must be submitted for all new grant/contract submissions, if you do not have previous approval by the IBC for the same infectious agent or toxin
IBC Questionnaire for Huam Subjects Studies:
- Use only for human gene transfer projects.
Annual Renewal/Project Modification form:
- This form is dual-purpose. It should be used for annual project reviews when required, or, it should also be used to make changes to previously approved projects when advanced approval is required for the modification (see revision policy and annual review policy).
What types of non-recombinant infectious agents and toxins must be reviewed by the IBC?
Infectious Agents are generally defined as risk group 2 agents and above (agents that can cause disease in healthy adult humans)
Use of Biologically Derived Toxins need only be reviewed by the IBC if the toxin is a select agent, or if the toxin is lethal for vertebrates at an LD 50 of less than 100 nanograms per kilogram body weight.
What are recombinant or synthetic nucleic acid molecules?In the context of the NIH Guidelines, recombinant and synthetic nucleic acids are defined as:
(i) molecules that a) are constructed by joining nucleic acid molecules and
b) that can replicate in a living cell, i.e., recombinant nucleic acids;
(ii) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those
that are chemically or otherwise modified but can base pair with naturally occurring
nucleic acid molecules, i.e., synthetic nucleic acids, or
(iii) molecules that result from the replication of those described in (i) or (ii) above.
That means research projects involving the use of all recombinant plasmids/vectors/viruses, even though many are exempt, should be submitted to the IBC for review (exempt determination should be made by IBC).
What Research with synthetic nucleic acid molecules is covered by the NIH Guidelines?
The NIH has issued FAQs regarding the March 5th, 2103 revision to the NIH Guidelines to include synthetic nucleic acid molecules which addresses this question in depth.
Research with synthetic nucleic acid molecules, or their DNA or RNA derivatives, is covered by the NIH Guidelines if the nucleic acid molecule is being used in cells, organisms, or viruses and if it:
- has the potential to replicate in cells (e.g. a chemically synthesized virus or sequence contains an origin of replication)
- can integrate into genomic DNA (e.g. contains cis elements involved in integration)
- encodes a toxin lethal for vertebrates with an LD50 of <100 ng/kg
- or use of synthetic nucleic acid molecules >100 nucleotides in human subjects
The following types of research with synthetic nucleic acid molecules would typically be exempt:
- nucleoside analogs (e.g. BrdU) in vitro or in vivo
- siRNAs, microRNAs, or morpholinos in vitro or in vivo
- the chemical synthesis of nucleic acid molecules (including PCR)
If the research project involves one of the above examples but may also meet one of the criteria for non-exempt synthetic nucleic acid research in the top four bullets, contact the IBC for a determination.
What are some examples of exempt and non-exempt research with recombinant DNA?
- use of standard laboratory strains of bacteria or yeast, such as K-12 strains of E. coli, S. cerevisiae, S. uvarum, or any asporogenic B. subtillis or B. licheniformis
- transfection of tissue culture cells with non-viral vectors (e.g. plasmids)
- the purchase, maintenance, and breeding of transgenic rodents, with few exceptions as outlined in the Transgenic Animal Review Policy
Non-exempt research includes (but is not limited to) use of:
- virally based vectors
- in vivo work with any vector or recombinantly modified cells
- non-standard host-vector systems (see Appendix C of the NIH Guidelines),
- experiments involving culture volumes that are > 10 liters
- vectors containing genes from Risk Group 3 or 4 organisms or genes for toxins lethal in vertebrates with an LD50<100ng/kg
How do I submit an rDNA or infectious agent/biologically-derived toxin project for review?
For a new project, submit the Initial rDNA Research Classification form or Infectious Agent/Toxin Questionnaire (see Guide to Forms and Usage).
Investigators should also make sure they have completed the rDNA portion of the required responsible conduct of research (check your record by logging onto Big Brain, and the infectious agent shipping module if applicable*.
*Training is required for all individuals who package, handle, or prepare paperwork for the shipment of hazardous materials, including infectious substances.
For Recombinant DNA Research:
For exempt projects where exempt determination can be made from the initial form, an exempt letter will be sent to the investigator. If more information is required, the investigator will be asked to complete the rDNA Research Questionnaire (RDRQ).
The RDRQ should be completed in full, with a description of the vectors, packaging systems, etc used in order to be reviewed and approved by the IBC. Please be sure to include a reference or product information specifically describing the details of the vector system (see the instruction guide here).