Unravelling the essential elements for recombinant adeno-associated virus (rAAV) production in animal cell-based platforms

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology advances Pub Date : 2024-04-29 DOI:10.1016/j.biotechadv.2024.108370

David Catalán-Tatjer , Konstantina Tzimou , Lars K. Nielsen , Jesús Lavado-García

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Abstract

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.

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揭示基于动物细胞平台的重组腺相关病毒（rAAV）生产的基本要素

重组腺相关病毒（rAAV）处于基因治疗应用的最前沿，其安全高效的基因递送能力意义重大。由于对 rAAV 的需求不断增加且尚未得到满足，因此需要更全面地了解 AAV 的生物学特性及其对 rAAV 生产的影响。在这篇文献综述中，我们深入研究了 AAV 生物学和 rAAV 生产生物工艺，揭示了参与 rAAV 生产的蛋白质的功能和重要性。我们讨论了这些蛋白质之间的相互联系，以及它们如何影响 rAAV 生产平台的选择。通过解决现有的不一致性、文献空白和局限性，本综述旨在定义一组对 rAAV 生产至关重要的最小基因，为推进 rAAV 生物制造提供潜力，重点是最大限度地减少 rAAV 生产细胞内的基因负荷。

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来源期刊

Biotechnology advances 工程技术-生物工程与应用微生物

CiteScore

25.50

自引率

2.50%

发文量

167

审稿时长

37 days

期刊介绍： Biotechnology Advances is a comprehensive review journal that covers all aspects of the multidisciplinary field of biotechnology. The journal focuses on biotechnology principles and their applications in various industries, agriculture, medicine, environmental concerns, and regulatory issues. It publishes authoritative articles that highlight current developments and future trends in the field of biotechnology. The journal invites submissions of manuscripts that are relevant and appropriate. It targets a wide audience, including scientists, engineers, students, instructors, researchers, practitioners, managers, governments, and other stakeholders in the field. Additionally, special issues are published based on selected presentations from recent relevant conferences in collaboration with the organizations hosting those conferences.