Effect of Administration Route on the Biodistribution and Shedding of Replication-Deficient AAV2: A Qualitative Modelling Approach

Esther      F.A. Brandon; Harm      P.H. Hermsen; Jan      C.H. van Eijkeren; Birgitte      Tiesjema

Abstract

Gene therapy is a rapidly developing field in which recombinant nucleic acid sequences are introduced to individuals to regulate, repair, replace, add or delete a genetic sequence. Recombinant adeno-associated viral (AAV) vectors, especially AAV2, are frequently used in gene therapy. Knowledge on the biodistribution and potential shedding of AAV2 is crucial to evaluate the risks of infection with the viral vector for the patient and the environment. Literature was analysed for biodistribution and shedding data for AAV2. Preclinical and clinical studies were included with a focus on the influence of the administration route on spreading. Based on biodistribution and shedding data, a qualitative model for the biodistribution and shedding of AAV2 related to the administration route is presented. It is concluded that biodistribution and shedding of AAV2 depend on the route of administration. Some routes lead to local biodistribution and thus to no shedding or shedding via one route only. Other routes lead to systemic biodistribution and to shedding via several excretion routes. The qualitative model presented can help to determine the possible biodistribution in the body and the risk of shedding via the different excretion routes. In addition, it can help to predict the different shedding routes after a certain administration route of AAV2 and thus in deciding which studies are warranted or which safety precautions are needed after administration to patients.

Keywords: Viral vectors, adeno-associated virus, excretion, distribution, gene therapy, qualitative model

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