Current processes for the production of recombinant adeno-associated virus (rAAV) are inadequate to meet the surging demand for rAAV-based gene therapies. This article reviews recent advances that hold the potential to address current limitations in rAAV manufacturing. A multidisciplinary perspective on technological progress in rAAV production is presented, underscoring the necessity to move beyond incremental refinements and adopt a holistic strategy to address existing challenges. Since several recent reviews have thoroughly covered advancements in upstream technology, this article provides only a concise overview of these developments before moving to pivotal areas of rAAV manufacturing not well covered in other reviews, including analytical technologies for rapid and high-throughput measurement of rAAV quality attributes, mathematical modeling for platform and process optimization, and downstream approaches to maximize efficiency and rAAV yield. Novel technologies that have the potential to address the current gaps in rAAV manufacturing are highlighted. Implementation challenges and future research directions are critically discussed.

中文翻译：

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应对 rAAV 基因疗法制造挑战的技术进步状况


目前重组腺相关病毒 (rAAV) 的生产工艺不足以满足基于 rAAV 的基因疗法不断增长的需求。本文回顾了有望解决 rAAV 制造当前局限性的最新进展。提出了 rAAV 生产技术进步的多学科视角，强调了超越渐进式改进并采取整体战略来应对现有挑战的必要性。由于最近的几篇评论已经全面涵盖了上游技术的进步，因此本文仅对这些发展进行简要概述，然后再转向其他评论中未充分涵盖的 rAAV 制造的关键领域，包括用于快速和高通量测量 rAAV 质量的分析技术属性、平台和流程优化的数学模型，以及最大化效率和 rAAV 产量的下游方法。重点介绍了有潜力解决 rAAV 制造当前差距的新技术。批判性地讨论了实施挑战和未来的研究方向。