Department of Biomedical Engineering and Biotechnology, The University of Massachusetts Lowell, Lowell, Massachusetts, USA.
Department of Chemical Engineering, The University of Massachusetts Lowell, Lowell, Massachusetts, USA.
Biotechnol Bioeng. 2023 Sep;120(9):2601-2621. doi: 10.1002/bit.28412. Epub 2023 May 1.
Gene therapy is a promising therapeutic approach for genetic and acquired diseases nowadays. Among DNA delivery vectors, recombinant adeno-associated virus (rAAV) is one of the most effective and safest vectors used in commercial drugs and clinical trials. However, the current yield of rAAV biomanufacturing lags behind the necessary dosages for clinical and commercial use, which embodies a concentrated reflection of low productivity of rAAV from host cells, difficult scalability of the rAAV-producing bioprocess, and high levels of impurities materialized during production. Those issues directly impact the price of gene therapy medicine in the market, limiting most patients' access to gene therapy. In this context, the current practices and several critical challenges associated with rAAV gene therapy bioprocesses are reviewed, followed by a discussion of recent advances in rAAV-mediated gene therapy and other therapeutic biological fields that could improve biomanufacturing if these advances are integrated effectively into the current systems. This review aims to provide the current state-of-the-art technology and perspectives to enhance the productivity of rAAV while reducing impurities during production of rAAV.
基因治疗是当今治疗遗传和获得性疾病的一种很有前途的方法。在 DNA 传递载体中，重组腺相关病毒（rAAV）是商业药物和临床试验中使用的最有效和最安全的载体之一。然而，rAAV 生物制造的当前产量落后于临床和商业用途所需的剂量，这集中反映了宿主细胞中 rAAV 的低生产率、rAAV 生产生物工艺的可扩展性困难以及生产过程中产生的高杂质水平。这些问题直接影响了市场上基因治疗药物的价格，限制了大多数患者接受基因治疗的机会。在这种情况下，本文综述了与 rAAV 基因治疗生物工艺相关的当前实践和几个关键挑战，并讨论了 rAAV 介导的基因治疗和其他治疗性生物领域的最新进展，如果这些进展能够有效地整合到现有系统中，这些进展可能会提高生物制造的效率。本综述旨在提供当前的最新技术和观点，以提高 rAAV 的生产率，同时降低 rAAV 生产过程中的杂质。
