Adeno-Associated Virus (AAV)

Safety Data Sheet - Infectious Substances

Section I - Infectious Agent

Name: Adeno-associated Virus (AAV) serotype 2 recombinant vectors.

Characteristics: Parvoviridae; icosahedral, 20-25 nm in diameter; single stranded DNA genome with protein capsid. AAV is dependent for replication on presence of wild type adenovirus or herpesvirus; in the absence of helper virus, AAV will stably integrate into the host cell genome. Co-infection with helper virus triggers lytic cycle as do some agents which appropriately perturb host cells. Transduction does not appear to require cell division.

Biosafety Level: NIH BSL 2

Section II - Health Hazard

Pathogenicity: No known pathology for wild type AAV serotype 2. Wild type AAV integrates preferentially into human chromosome 19q13.3-qter; recombinant vectors lose this specificity and appear to integrate randomly, thereby posing a theroretical risk of insertional mutagenesis.

Host Range: Human, will infect a range of mammalian cells.

Mode of Transmission: Not documented definitively. Infection apparently via mouth, esophageal, or intestinal mucosa.

Incubation Period: No symptoms apparent.

Section III - Viability

Drug susceptibility: No specific anti-viral available.

Susceptibility to Disinfectants: Susceptibile to 5% phenol, 10% bleach, or 10% Wescodyne. Recommend fresh solution of 10% bleach for 30 minutes.

Physical Inactivation: Resistant to inactivation by pH 3-9 or to 60 oC for 1 hour. Recommend treatment of items for disposal (chemically decontaminated or not) by incineration (BFI at UCSD) or by steam sterilization for 60 minutes.

Survival Outside of Host: AAV's resistance to physical inactivation permits survival outside host organisms for up to several weeks under normal environmental conditions.

Section IV - Medical

Surveillance: Pre-employment serum sample.

First Aid/Treatment: Because of the possibility of adenovirus contamination, recommended treatment is the same as for adenovirus exposure. For splashes to the eye of material containing virus, rinse eye at eyewash for 15 minutes then report to hospital emergency room (UCSD - Jacobs Medical Center or Hillcrest) for evaluation. A serum sample should be taken as soon as possible (at UCSD this is done by Occupational Health, phone 274-6206). In the case of accidental injection of material containing virus, wash area well with soap and water then contact office of Occupational Health for advice, evaluation and serum sample. At UCSD, notify supervisor and EH&S as soon as possible after exposure.

Immunization: None available.

Prophylaxis: None available.

Section V - Laboratory Hazards

Laboratory - acquired infections:

Sources/Specimens: Theoretical risk from exposure to laboratory cultures of recombinant virus.

Primary Hazards: Ingestion, droplet exposure of the mucous membrane, direct injection.

Special Hazards: Contact with feces or urine from infected animals for 72 hours post infection. Because residual helper virus may not be completely inactivated during AAV purification, helper virus risks must be assessed. The Vector Development laboratory uses Adenovirus 5 as a helper virus.

Section VI - Recommended Precautions

Containment Requirements: Biosafety level 2 plus UCSD Adeno special practices and BSL 2 containment facilities for all activities involving the virus, recombinant virus vectors, and potentially infectious body fluids or tissues.

Protective Clothing: Laboratory coat, gloves, N-95 mask, goggles; as for Adenovirus.

Section VII - Handling Information

Spills: Allow aerosols to settle 15 minutes; wear protective clothing and gently cover the spill with adsorbent paper towel and apply freshly prepared 10% sodium hypochlorite starting at the perimeter and workingtowards the center; allow at least 30 minutes contact time before clean up.

Disposal: Decontaminate all wastes before disposal; steam sterilization, incineration, chemical disinfection. At UCSD contaminated material may be sealed in labeled, doubled, red biohazard bags, transported in covered, leak proof containers to BFI disposal bins for eventual incineration.

Storage: In sealed containers that are appropriately labeled and in approved locations for BSL 2 materials at -700C.

Transport: Material must be sealed in primary and secondary containers, appropriately labeled.

Section VIII - Transgenes and Other Foreign Genetic Elements

Considerations: What is the replication status of your vector? In general, recombinant Ad 5 vectors produced in the Vector Development laboratory are replication incompetent. What is the nature of the transgene/s - are any potentially hazardous transgenes expressed, i.e.. toxins, oncogenes? Have any foreign elements been introduced which alter the specificity, host range, stability, or titer of the resulting vector?

It is imperative that those handling recombinant vectors consider both the nature of the virus used as a vector and the effects of any transgene, introduced genetic elements, or other modification.

 

Prepared by UCSD Program in Human Gene Therapy staff. Reviewed by UCSD Office of Environmental Health Safety. We accept no responsibility for the accuracy, sufficiency, or reliability of this information or for any loss or injury resulting from the use of this information. (written August 20, 1998)