Biodistribution and shedding of adeno-associated viruses (AAV)

Genetic engineering work with various recombinant AAV serotypes was included in the general ZKBS statement from 2005 (Ref. 6790-10-73) Security levels 1 (for AAV-1 to -3, AAV-3b, AAv-5, AAV6, AAV-8, AAV-9 and AAV-rh10) or Security level 2 (AAV-4, AAV-7, AAV 10 to -13). The statement was already supplemented in April 2021 with a recommendation for the handling of AAV-infected animals ( AGCT-Gentechnik. report from 30.04.2021 and in October 2021 for a note on disinfection measures ( AGCT-Gentechnik. report from 29.10.2021 The updated opinion of November 2024 includes, among other things, a new section on biodistribution, stability and shedding (excretion) of virus particles (section 2.2). In addition, serotypes AAV-4, AAV-7, and AAV-10 to -13 are downgraded to risk group 1.

For some of the AAV serotypes, despite different parameters (dose, promoter, transgene, species), general statements can be made about their Tropism The tropism of AAV depends on which cellular receptors the respective serotype binds to. How long and how many infectious AAV particles remain in certain tissues depends, among other things, on the species, the dose used, the type and degree of perfusion of the tissue, and the status of the immune system. Pseudotyping, however, can change cell tropism and thus the residence time of the particles and their shedding. Studies in mice indicate that different AAV serotypes are eliminated from the vascular system at different rates under the same conditions.

The shedding of infectious viral particles is also influenced by various factors. Data from studies suggest that stable AAV particles can persist for longer periods, for example, in patient serum and rabbit semen (several weeks) or in mouse feces, urine, and saliva (up to 5 days).

Therefore, no general statement can be made as to the point at which treated laboratory animals no longer release infectious AAV particles and are therefore no longer considered carriers of GMOs. Therefore, the information in the ZKBS statement mentioned under point 3 in Section 2.6 must be observed.

The updated ZKBS statement can be found under the reference number Ref. No. 6790-10-73 can be retrieved.

Editor's note: Please note that the updated statement of the ZKBS is incorrectly linked in the ZKBS communications on the 258th meeting and is only correctly displayed via the " Statements on the comparability of genetic engineering work " route.