Bovine AAV: A promising vector for pulmonary gene therapy
4 affiliations
- 1Novartis Biomedical Research, Basel 4056, Switzerland
- 2Novartis Biomedical Research, San Diego, CA 92121, USA
- 3Novartis Biomedical Research, Cambridge, MA 02139, USA
- 4University of Basel, Faculty of Science, Department of Pharmaceutical Sciences, Basel 4056, Switzerland
Abstract
Efficient systemic delivery to the lung remains a major barrier for adeno-associated virus (AAV)-mediated pulmonary gene therapy, particularly when pre-existing immunity limits the use of conventional capsids. Here, we evaluated Bovine AAV, a phylogenetically divergent capsid, as a candidate vector for lung-directed gene transfer. In adult C57BL/6J mice, intravenous delivery of Bovine AAV resulted in robust and preferential lung transduction comparable with AAV4, with predominant targeting of alveolar type I pneumocytes and pulmonary endothelial cells. In primary human lung-resident cells, Bovine AAV was particularly effective in microvascular endothelial cells, a target poorly transduced by AAV4 in vitro. Bovine AAV demonstrated scalable production with yield, purification performance, capsid quality, and genome integrity comparable to AAV9. In sera from healthy adults from the United States and Switzerland, Bovine AAV showed intermediate neutralization frequencies, lower than AAV2 and AAV4 but higher than AAV5 and AAV9. Of relevance, Bovine AAV maintained in vivo transduction efficiency in mice previously immunized with a pool of human and non-human primate-derived AAV capsids, including AAV4. Together, these results position Bovine AAV as a promising lung-tropic and immune-distinct vector for pulmonary gene therapy, with particular relevance for applications requiring systemic delivery in the presence of pre-existing immunity to conventional serotypes.
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BibTeX
@article{ivan2026bovine,
title = {{Bovine AAV: A promising vector for pulmonary gene therapy}},
author = {Daniela C. Ivan and Valerie Dubost and Laura Israel and Jonas Weinmann and Dennis Ungan and Nina Carbonetti and Nathalie Stuber and Magali Jivkov and Esther Erard and Elisabetta Biglieri and Federica De Girardi and Simon Mittermeier and Maryam Syed and Bruno Tigani and Najwa Ouali Alami and Kristin Dreessen and Colin Deniston and Kannan Sankar and Laura Bollepalli and Vanessa Cornacchione and Elisabetta Traggiai and Dominique Brees and Anette Karle and José M. Carballido and Agostino Cirillo},
journal = {Molecular Therapy Advances},
year = {2026},
month = oct,
doi = {10.1016/j.omta.2026.201859},
url = {https://doi.org/10.1016/j.omta.2026.201859},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Bovine AAV: A promising vector for pulmonary gene therapy
AU - Daniela C. Ivan
AU - Valerie Dubost
AU - Laura Israel
AU - Jonas Weinmann
AU - Dennis Ungan
AU - Nina Carbonetti
AU - Nathalie Stuber
AU - Magali Jivkov
AU - Esther Erard
AU - Elisabetta Biglieri
AU - Federica De Girardi
AU - Simon Mittermeier
AU - Maryam Syed
AU - Bruno Tigani
AU - Najwa Ouali Alami
AU - Kristin Dreessen
AU - Colin Deniston
AU - Kannan Sankar
AU - Laura Bollepalli
AU - Vanessa Cornacchione
AU - Elisabetta Traggiai
AU - Dominique Brees
AU - Anette Karle
AU - José M. Carballido
AU - Agostino Cirillo
PY - 2026
DA - 2026/10/05
JO - Molecular Therapy Advances
DO - 10.1016/j.omta.2026.201859
UR - https://doi.org/10.1016/j.omta.2026.201859
AB - Efficient systemic delivery to the lung remains a major barrier for adeno-associated virus (AAV)-mediated pulmonary gene therapy, particularly when pre-existing immunity limits the use of conventional capsids. Here, we evaluated Bovine AAV, a phylogenetically divergent capsid, as a candidate vector for lung-directed gene transfer. In adult C57BL/6J mice, intravenous delivery of Bovine AAV resulted in robust and preferential lung transduction comparable with AAV4, with predominant targeting of alveolar type I pneumocytes and pulmonary endothelial cells. In primary human lung-resident cells, Bovine AAV was particularly effective in microvascular endothelial cells, a target poorly transduced by AAV4 in vitro. Bovine AAV demonstrated scalable production with yield, purification performance, capsid quality, and genome integrity comparable to AAV9. In sera from healthy adults from the United States and Switzerland, Bovine AAV showed intermediate neutralization frequencies, lower than AAV2 and AAV4 but higher than AAV5 and AAV9. Of relevance, Bovine AAV maintained in vivo transduction efficiency in mice previously immunized with a pool of human and non-human primate-derived AAV capsids, including AAV4. Together, these results position Bovine AAV as a promising lung-tropic and immune-distinct vector for pulmonary gene therapy, with particular relevance for applications requiring systemic delivery in the presence of pre-existing immunity to conventional serotypes.
SN - 3117-387X
ER -