Recombinant adeno-associated virus (rAAV) are the leading vector for gene therapies.

Their manufacturing still poses a challenge for the biopharmaceutical industry.

The essentiality of the different elements for their production has been analyzed.

The minimal set of genes, proteins and interactions have been identified.

These elements were analyzed for the different available cell-based platforms.

Recombinant adeno-associated viruses (rAAVs) stand at the forefront of gene therapy applications, holding immense significance for their safe and efficient gene delivery capabilities. The constantly increasing and unmet demand for rAAVs underscores the need for a more comprehensive understanding of AAV biology and its impact on rAAV production. In this literature review, we delved into AAV biology and rAAV manufacturing bioprocesses, unravelling the functions and essentiality of proteins involved in rAAV production. We discuss the interconnections between these proteins and how they affect the choice of rAAV production platform. By addressing existing inconsistencies, literature gaps and limitations, this review aims to define a minimal set of genes that are essential for rAAV production, providing the potential to advance rAAV biomanufacturing, with a focus on minimizing the genetic load within rAAV-producing cells.

Adeno-associated virus

Essential elements

Manufacturing

Gene therapy

rAAV

© 2024 The Authors. Published by Elsevier Inc.