Assessment of cell-binding capacity of shed rAAV particles after gene therapy vector administration: implications for environmental risk and hygiene recommendations.

Background: Currently, adeno-associated viruses (AAVs) are the most commonly used in vivo gene therapy (GT) vector platform. Risks posed to the environment, including the public, have not been well studied in the past. There is uncertainty concerning the necessary level of biocontainment and appropriate hygiene behavior for the handling of secreta/excreta of GT patients during the shedding phase.

Research design and methods: Here, feces and urine samples from non-human primates, treated with an AAV9-based vector at 2 × 10¹³ vector genomes per kilogram body weight (vg/kg), were analyzed for vector presence and subsequently analyzed for their capacity to bind to cells.

Results: Both sample types contained particles which bound to cells at concentrations in the range of ~10⁴ (and higher) vg/mL of culture medium. Novel control rAAV vector displayed a ~2-3 orders of magnitude higher affinity to cells than shed particles.

Conclusions: The lower binding capacity of the shed vector particles speaks in favor of a more relaxed containment and hygiene approach in the context of GT. It is recommended that current hygiene and contact-avoidance-based containment measures after GT administration are reduced. The results also support the efforts to achieve a simplification of the regulatory review process of medicinal genetically modified organisms.