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Unravelling the essential elements for recombinant adeno-associated virus (rAAV) production in animal cell-based platforms
Biotechnology Advances ( IF 16.0 ) Pub Date : 2024-04-29 , DOI: 10.1016/j.biotechadv.2024.108370
David Catalán-Tatjer , Konstantina Tzimou , Lars K. Nielsen , Jesús Lavado-García

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.

中文翻译:


揭示在动物细胞平台中生产重组腺相关病毒 (rAAV) 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,因其安全高效的基因传递能力具有巨大意义。对 rAAV 不断增长且未得到满足的需求强调需要更全面地了解 AAV 生物学及其对 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 制造生物过程,揭示了 rAAV 生产中涉及的蛋白质的功能和必要性。我们讨论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、文献空白和局限性,本综述旨在定义 rAAV 生产所必需的最小基因组,提供推进 rAAV 生物制造的潜力,重点是最大限度地减少 rAAV 生产细胞内的遗传负荷。
更新日期:2024-04-29
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