Gurazada Sai Guna Ranjan, Kennedy Hannah M, Braatz Richard D, Mehrman Steven J, Polson Shawn W, Rombel Irene T
Center for Bioinformatics and Computational Biology, Department of Computer and Information Sciences, University of Delaware, Newark, DE, United States.
BioCurie, Inc., Wilmington, DE, United States.
Biotechnol Adv. 2025 Mar-Apr;79:108506. doi: 10.1016/j.biotechadv.2024.108506. Epub 2024 Dec 19.
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.
基因治疗正准备从小众医学过渡到主流医学，重组腺相关病毒（rAAV）是首选载体。然而，需要强大、可扩展的工业化生产来满足需求并为患者提供可负担的途径，但这尚未实现。弥合供需差距需要生物制造方面的创新，以实现rAAV产品产量和质量的关键突破。组学提供了丰富的机制知识来源，可应用于HEK293，这是rAAV生产中最常用的细胞系。在这篇综述中，探讨了越来越多将基因组学、表观基因组学、转录组学、蛋白质组学和代谢组学应用于HEK293生物生产的不同研究的结果。来自CHO组学的经验教训，即应用组学方法改善CHO生物生产，为探索“HEK组学”的潜力提供了一个框架，“HEK组学”作为一种多组学信息方法，可为提高HEK293中rAAV和其他重组产品的瞬时和稳定生产提供可操作的机制见解。
