@ARTICLE{10.3389/fbioe.2021.762209, AUTHOR={Arotcarena, Marie-Laure and Dovero, Sandra and Biendon, Nathalie and Dutheil, Nathalie and Planche, Vincent and Bezard, Erwan and Dehay, Benjamin}, TITLE={Pilot Study Assessing the Impact of Intrathecal Administration of Variants AAV-PHP.B and AAV-PHP.eB on Brain Transduction in Adult Rhesus Macaques}, JOURNAL={Frontiers in Bioengineering and Biotechnology}, VOLUME={9}, YEAR={2021}, URL={https://www.frontiersin.org/articles/10.3389/fbioe.2021.762209}, DOI={10.3389/fbioe.2021.762209}, ISSN={2296-4185}, ABSTRACT={Adeno-associated virus (AAV) vectors are increasingly used as an effective and safe approach to deliver genetic material to the central nervous system (CNS). The AAV9-derived variants, AAV-PHP. B and AAV-PHP.eB, reportedly broadly transduce cells throughout the CNS compared to the original serotype 9, AAV9. As non-human primate data are scarce, we here evaluated the CNS transduction efficiencies after lumbar intrathecal bolus delivery of identical doses of either AAV-PHP. B:CAG-EGFP or AAV-PHP. eB:CAG-EGFP in rhesus macaque monkeys. AAV-PHP.eB achieved a more efficient and widespread CNS transduction compared to AAV-PHP.B. We report a strong neuronal and oligodendroglial tropism for both variants in the putamen and in the hippocampus. This proof-of-concept experiment highlights the potential value of intrathecal infusions of AAV-PHP.eB to distribute genetic material in the CNS with cell-type specificity and introduces a new opportunity to model brain diseases in rhesus macaque monkeys and further develop gene therapies targeting the CNS in humans.} }