I: Background and Purpose: 

Replication-defective viral vectors are commonly used in animal research applications. When administered to animals, unincorporated viral vectors may be shed in the urine or feces. While designed to be replication deficient, recombinant viral vectors pose a potential risk to humans and other species since they are designed to carry genes of interest into cells for expression (“single round infection”).  Other risks include off target effects for vectors designed to integrate into the host cell genome or hazards associated with the transgene itself (i.e. known/potential oncogenes or expressing toxins). To comply with biosafety and NIH Guidelines requirements (App. G-II.) for the destruction of all recombinant materials before disposal, all animal bedding and caging equipment used with recombinant viral vectors must be decontaminated before washing or disposal. 

II: Related Policy and Guidance:

·      Policy# 529-345 Tamoxifen, Bromodeoxyuridine (BrdU), and other non-radioactive DNA Precursors - Treatment in Rodents

·      Policy# 529-301 Personal Protective Equipment (PPE) for Lab Animal Care and Use

Experiments containing replication-defective viral vectors in rodents must adhere to protocols, procedures, and biosafety/containment level approved by the Institutional Animal Care and Use Committee (IACUC) and the Institutional Biosafety Committee (IBC).  In addition:

1.      Cage cards must include the following information:

·      Name of the viral vector or agent

·      Date(s) the viral vector was administered

·      The animal species

·      The name and emergency contact telephone number of the PI or other responsible individual

·      Any special requirements for entering the laboratory or handling of cages (such as PPE)

·      For animals inoculated with a viral vector that requires ABSL-2 and above containment, the room door sign and the cage card must include the biohazard symbol during the first 72 hours after inoculation and prior to the first cage change.  After 72 hours and the first cage change, the biohazard symbol can be removed from the cage card and room door.

2.     Animals may be housed in reusable or disposable cages.  For any cage changes during the first 72 hours and first cage change after 72 hours,:

·      Reusable cages and other supplies must be decontaminated by 10% bleach or vivarium approved disinfectant prior to washing.  NOTE:  70% ethanol is NOT effective against adeno-associated virus (AAV). 

·      Disposable cages, bedding, and other disposable supplies must be disposed of as biohazardous waste.

3.     After administration of viral vectors to rodents, all cage changes within the first 72 hours and the first cage change after 72 hours must be performed by laboratory staff.  Following the first cage change after 72 hours, vivarium staff may take over standard husbandry duties.

4.     For viral vectors administered intravenously or intraperitoneally, the injection site should be wiped with disinfectant after administration as there are data that suggest inoculum can leak from the injection site.

III: References:

1) Assessment of Hazard Risk Associated with the Intravenous Use of Viral Vectors in Rodents. Reuter et al. 2012, Comparative Medicine 62:5

2) Biodistribution of rAAV following intraocular Administration – evidence for the presence and persistence of vector DNA in the optic nerve and in the brain. Provost et al. 2004, Molecular Therapy 11:2.

3) Preclinical Differences of intravascular AAV9 delivery to neurons and glia: A comparative study of adult mice and nonhuman primates. Gray et al. 2011, Molecular Therapy 19:6 (1058-1069).

4) Viral Vector Biosafety in Laboratory Animal Research. Collins et al. 2017, Comparative Medicine 67(3), 215-221.