Challenges in scaling up AAV-based gene therapy manufacturing

Ziyu Jiang; Paul A Dalby

doi:10.1016/j.tibtech.2023.04.002

Challenges in scaling up AAV-based gene therapy manufacturing

Trends Biotechnol. 2023 Oct;41(10):1268-1281. doi: 10.1016/j.tibtech.2023.04.002. Epub 2023 Apr 30.

Authors

Ziyu Jiang¹, Paul A Dalby²

Affiliations

¹ Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: z.jiang.19@ucl.ac.uk.
² Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: p.dalby@ucl.ac.uk.

PMID: 37127491
DOI: 10.1016/j.tibtech.2023.04.002

Abstract

Accelerating the scale up of adeno-associated virus (AAV) manufacture is highly desirable to meet the increased demand for gene therapies. However, the development of bioprocesses for AAV gene therapies remains time-consuming and challenging. The quality by design (QbD) approach ensures bioprocess designs that meet the desired product quality and safety profile. Rapid stress tests, developability screens, and scale-down technologies have the potential to streamline AAV product and manufacturing bioprocess development within the QbD framework. Here we review how their successful use for antibody manufacture development is translating to AAV, but also how this will depend critically on improved analytical methods and adaptation of the tools as more understanding is gained on the critical attributes of AAV required for successful therapy.

Keywords: adeno-associated virus; gene therapy; manufacturing; quality by design; scale down.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Commerce
Dependovirus* / genetics
Genetic Therapy*
Genetic Vectors / genetics
Quality Control