All work involving recombinant nucleic acids must be approved by the University of Arizona Institutional Biosafety Committee (IBC) as required by the NIH Guidelines for Research involving Recombinant or Synthetic Nucleic Acid Molecules. The IBC requires that all viral vectors used for transgene expression must:
- Be free of detectable replication-competent virus.
- Minimize probability of homologous and end joining recombination which might reestablish wild type virus.
- Be produced in the absence of helper virus.
- Utilize a homologous packaging system.
- Utilize self-inactivating derivatives.
The biosafety level of a viral vector defaults to the Risk Group (BSL-1, ABSL-1 or BSL-2 or ABSL-2) of the wild type viral strain from which the vector is derived. This biosafety level is applied during preparation, during use in cell culture systems and for the first 72 hours after inoculation into animals while the vector is considered infectious (though non-replicating). In addition, the transgene being inserted and the source of the viral vector should be considered.
The following checklist will assist in determining the proper biosafety level:
- Is the viral vector derived from a wild-type virus pathogenic to humans or primates (HIV, SIV, Human Adenovirus, etc.)?
- Does the transgene encode a product that is potentially hazardous (oncogene, toxin, etc.)?
- Does the vector or transgene encode more than 2/3 of the viral genome?
- Is the viral vector obtained from a non-commercial source?
If all responses are “NO”, then the viral vector can be handled at BSL-1 or ABSL-1 pending IBC approval. Examples of these types of vectors include AAV, murine retrovirus, FIV and VSV.
Exceptions must be requested using the IBC protocol review process. For example, an AAV vector made “in-house” must have safety data that shows it can be handled at ABSL-1.