Morphological and Molecular Detection of AAV Vector Genome and Transgene mRNA in the Oocytes of Female Cynomolgus Monkey Following Systemic Intravenous Administration

Abstract

Recombinant adeno-associated virus (rAAV) vectors have demonstrated their versatile utility for in vivo gene therapy to deliver successful treatment for several diseases of unmet medical needs. The polytropic nature of AAV permitted targeting diverse tissue types to support various diseases; however, it also resulted in vector transduction of non-target organs, including the gonads of males and females, which subsequently confer an additional investigation to derisk any potential germ cell transduction and/or germline transmission following rAAV administration. While a plethora of data is available for male gonad assessment, primarily due to the feasibility of longitudinal semen collection, there is a paucity of data on oocyte transduction by rAAV due to challenges with oocyte collection. In this brief report, we share polymerase chain reaction and in situ hybridization data on oocyte transduction in a female cynomolgus macaque 4 weeks following systemic intravenous administration of an engineered rAAV and discuss the significance and potential mitigation strategies of such findings in the process of AAV-based gene therapy product development.