Integrated Continuous Biomanufacturing of Recombinant Adeno-Associated Virus
- 1Institute of Pharma Technology and Biotechnology, FHNW University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland
Abstract
Recombinant adeno-associated virus (rAAV) manufacturing remains constrained by low yields, costly purification, and process complexity, limiting cost-effective access to gene therapy. Here, we demonstrate an integrated continuous biomanufacturing platform that transfers proven antibody-manufacturing technology to rAAV production by coupling perfusion to semi-continuous twin-column affinity capture (CaptureSMB). This architecture enables continuous harvest of extracellular rAAV without cell lysis, depth filtration, or endonuclease treatment, sustaining stable operation over five days. Relative to conventional batch processing, perfusion improved capsid or vector genome yield depending on the production process, while affinity capture alone reduced total DNA to batch-comparable levels, with no measurable loss in impurity clearance or potency. By consolidating multiple manual unit operations into one continuous workflow, the platform may reduce manual intervention and process footprint. Its modular design may generalize to other rAAV serotypes, inducible producer cell lines, and viral vector classes, offering a potential route toward more efficient gene therapy manufacturing.
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BibTeX
@misc{plieninger2026integrated,
title = {{Integrated Continuous Biomanufacturing of Recombinant Adeno-Associated Virus}},
author = {R. Plieninger and J. M. Mueller and D. Tobler and E. Saygili and P. Werder and Y. Higuchi and R. Takahashi and V. Sebastian and T. Mueller-Spaeth and S. Goebel and T. K. Villiger},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.751635},
url = {https://www.biorxiv.org/content/10.64898/2026.09.14.751635v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Integrated Continuous Biomanufacturing of Recombinant Adeno-Associated Virus
AU - R. Plieninger
AU - J. M. Mueller
AU - D. Tobler
AU - E. Saygili
AU - P. Werder
AU - Y. Higuchi
AU - R. Takahashi
AU - V. Sebastian
AU - T. Mueller-Spaeth
AU - S. Goebel
AU - T. K. Villiger
PY - 2026
DA - 2026/09/14
PB - bioRxiv
DO - 10.64898/2026.09.14.751635
UR - https://www.biorxiv.org/content/10.64898/2026.09.14.751635v1
AB - Recombinant adeno-associated virus (rAAV) manufacturing remains constrained by low yields, costly purification, and process complexity, limiting cost-effective access to gene therapy. Here, we demonstrate an integrated continuous biomanufacturing platform that transfers proven antibody-manufacturing technology to rAAV production by coupling perfusion to semi-continuous twin-column affinity capture (CaptureSMB). This architecture enables continuous harvest of extracellular rAAV without cell lysis, depth filtration, or endonuclease treatment, sustaining stable operation over five days. Relative to conventional batch processing, perfusion improved capsid or vector genome yield depending on the production process, while affinity capture alone reduced total DNA to batch-comparable levels, with no measurable loss in impurity clearance or potency. By consolidating multiple manual unit operations into one continuous workflow, the platform may reduce manual intervention and process footprint. Its modular design may generalize to other rAAV serotypes, inducible producer cell lines, and viral vector classes, offering a potential route toward more efficient gene therapy manufacturing.
ER -