The state of technological advancement to address challenges in the manufacture of rAAV gene therapies

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances Pub Date : 2024-08-20 DOI:10.1016/j.biotechadv.2024.108433

Francesco Destro , Weida Wu , Prasanna Srinivasan , John Joseph , Vivekananda Bal , Caleb Neufeld , Jacqueline M. Wolfrum , Scott R. Manalis , Anthony J. Sinskey , Stacy L. Springs , Paul W. Barone , Richard D. Braatz

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Abstract

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.

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应对 rAAV 基因疗法生产挑战的技术发展状况。

目前的重组腺相关病毒（rAAV）生产工艺不足以满足对基于 rAAV 的基因疗法日益增长的需求。本文回顾了有可能解决目前 rAAV 生产限制的最新进展。文章从多学科角度阐述了 rAAV 生产技术的进步，强调了超越渐进式改进并采取整体战略应对现有挑战的必要性。由于最近的几篇综述已全面介绍了上游技术的进展，本文仅简要概述了这些进展，然后探讨了其他综述未充分涉及的 rAAV 生产的关键领域，包括用于快速、高通量测量 rAAV 质量属性的分析技术，用于平台和流程优化的数学建模，以及最大限度提高效率和 rAAV 产量的下游方法。重点介绍了有可能解决当前 rAAV 生产差距的新技术。此外，还对实施过程中遇到的挑战和未来的研究方向进行了深入探讨。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.