HEK-omics: The promise of omics to optimize HEK293 for recombinant adeno-associated virus (rAAV) gene therapy manufacturing

Sai Guna Ranjan Gurazada; Hannah M Kennedy; Richard D Braatz; Steven J Mehrman; Shawn W Polson; Irene T Rombel

doi:10.1016/j.biotechadv.2024.108506

HEK-omics: The promise of omics to optimize HEK293 for recombinant adeno-associated virus (rAAV) gene therapy manufacturing

Biotechnol Adv. 2024 Dec 19:108506. doi: 10.1016/j.biotechadv.2024.108506. Online ahead of print.

Authors

Sai Guna Ranjan Gurazada¹, Hannah M Kennedy², Richard D Braatz³, Steven J Mehrman⁴, Shawn W Polson⁵, Irene T Rombel⁶

Affiliations

¹ Center for Bioinformatics and Computational Biology, Department of Computer and Information Sciences, University of Delaware, Newark, DE, United States.
² BioCurie, Inc., Wilmington, DE, United States.
³ Massachusetts Institute of Technology, Cambridge, MA, United States.
⁴ Janssen Research & Development, Janssen Pharmaceuticals, Johnson & Johnston, Malvern, PA, United States.
⁵ Center for Bioinformatics and Computational Biology, Department of Computer and Information Sciences, University of Delaware, Newark, DE, United States. Electronic address: polson@udel.edu.
⁶ BioCurie, Inc., Wilmington, DE, United States. Electronic address: irene@biocurie.com.

PMID: 39708987
DOI: 10.1016/j.biotechadv.2024.108506

Abstract

Gene therapy is poised to transition from niche to mainstream medicine, with recombinant adeno-associated virus (rAAV) as the vector of choice. However, robust, scalable, industrialized production is required to meet demand and provide affordable patient access, which has not yet materialized. Closing the chasm between demand and supply requires innovation in biomanufacturing to achieve the essential step change in rAAV product yield and quality. Omics provides a rich source of mechanistic knowledge that can be applied to HEK293, the most commonly used cell line for rAAV production. In this review, the findings from a growing number of diverse studies that apply genomics, epigenomics, transcriptomics, proteomics, and metabolomics to HEK293 bioproduction are explored. Learnings from CHO-Omics, application of omics approaches to improve CHO bioproduction, provide a framework to explore the potential of "HEK-Omics" as a multi-omics-informed approach providing actionable mechanistic insights for improved transient and stable production of rAAV and other recombinant products in HEK293.

Keywords: Adeno-associated virus; Biomanufacturing; Gene therapy; HEK293; Omics; rAAV.

Publication types

Review