Recombinant DNA

Recombinant DNA

Investigators conducting experiments with recombinant DNA (rDNA) experiments are required to read and follow the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). The NIH Guidelines categorizes rDNA experiments and provide compliance requirements for each of these categories. For the most part, Oakland University rDNA experiments will fall into one of three experiment categories:

1. Exempt Experiments, 
2. Experiments Requiring Prior Approval,
3. Experiments Requiring IBC Notice Simultaneous with Initiation

If you believe your rDNA experiments will be exempt, please complete the Exempt rDNA Form. If after completing the form you realize your work is not exempt then you must register your experiment online using Oakland University’s Research Application Manger: RAM 3.0.

Investigator Responsibilities

Institutions that receive funding from NIH are required to follow the NIH Guidelines. This includes all researchers at the institution regardless of the funding source. Investigators should start with the NIH Brochure for Investigators for a summary of their responsibilities when conducting research at an institution which accepts NIH funding.

CRISPR Technology

The powerful gene-editing technology referred to as “CRISPR” has a number of risks that the IBC and investigators must consider when approving a project, but there are two applications where the technology poses significant risks.

1. CRISPR experiments where the guide RNA can target a human gene, whether it is intentional or as an off-target event.
2. “Gene Drive” experiments which increase the spread of genetic elements in a population much quicker than what occurs naturally. Experiments where there is a risk of creating a gene drive system must be carefully evaluated to prevent unintended ecological effects.

Investigators must conduct a careful risk assessment of their rDNA experiments especially those utilizing viral vectors and CRISPR technology. Careful consideration should be given to the potential effects of accidental worker exposure and to the creation of gene drive systems. The following are points to consider:

1. In mammalian cells CRISPR silencing is permanent and transmissible to off-spring.
2. Consider the gene function. For example, is the gene an oncogene (cancer causing), a regulatory gene or cell activator? (See: Viral Vectors and Transgene Containment)
3. Is the guide sequence specific to animals, humans or could it affect both? Is there a similarity between human and animal guide sequences?
4. What is the potential for off-target effects?
5. How much genotype change (dose) is needed for a physical effect?
6. How does route of exposure affect outcome?
7. Are CRISPR and the guide sequence(s) delivered at the same time, or during separate experiments?

The following online resources are useful when evaluating the human risks from, oncogenes, silencing or from overexpressing a gene used in your research:

Viral Vectors and Transgene Containment (Biosafety levels)
https://www.safety.duke.edu/sites/default/files/BSLevels_Common_Viral_Vectors.pdf

Gene Cards
http://www.genecards.org/

Mouse Genome Database
http://www.informatics.jax.org/batch

Atlas of Genetics and Cytogenetics in Oncology and Hematology
http://atlasgeneticsoncology.org/index.html