Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies.
Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies.
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基于重组腺相关病毒的基因疗法的过程和产品表征的分析方法。
DOI：
10.1016/j.omtm.2021.02.010
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发表时间：
2021-03-12
期刊：
影响因子：
--
通讯作者：
Braatz RD
中科院分区：
文献类型：
--
作者：
Gimpel AL;Katsikis G;Sha S;Maloney AJ;Hong MS;Nguyen TNT;Wolfrum J;Springs SL;Sinskey AJ;Manalis SR;Barone PW;Braatz RD
优化生产具有一致质量的重组腺相关病毒（rAAV）的上游和下游工艺取决于快速表征关键质量属性（cqa）的能力。在rAAV生产的背景下，病毒滴度、衣壳含量和聚集被确定为潜在的cqa，影响rAAV介导的基因治疗产品的效力、纯度和安全性。尽管快速、高通量的方法正在开始被开发和商业化，但是用于测量这些属性的分析方法通常受到长周转时间或低通量的过程开发的影响。这些方法尚未在学术或工业实践中得到很好的建立，而且支持数据很少。在这里，我们回顾了已建立的和即将出现的rAAV质量属性量化分析方法。在评估每种方法时，我们强调了快速、在线表征rAAV的进展。此外，我们发现，从传统方法向新方法过渡的一个关键挑战是缺乏与后者相关的学术和工业经验。本文献综述可为在raav介导的基因疗法的工艺开发过程中选择针对质量属性的分析方法提供指导，以实现快速、高通量的工艺表征。本文综述了基于raav的产品在开发过程中表征的分析方法。以载体滴度、含量比和聚合为重点，综述评估了已建立的和即将建立的方法，并为rAAV开发分析方法的选择提供指导。
The optimization of upstream and downstream processes for production of recombinant adeno-associated virus (rAAV) with consistent quality depends on the ability to rapidly characterize critical quality attributes (CQAs). In the context of rAAV production, the virus titer, capsid content, and aggregation are identified as potential CQAs, affecting the potency, purity, and safety of rAAV-mediated gene therapy products. Analytical methods to measure these attributes commonly suffer from long turnaround times or low throughput for process development, although rapid, high-throughput methods are beginning to be developed and commercialized. These methods are not yet well established in academic or industrial practice, and supportive data are scarce. Here, we review both established and upcoming analytical methods for the quantification of rAAV quality attributes. In assessing each method, we highlight the progress toward rapid, at-line characterization of rAAV. Furthermore, we identify that a key challenge for transitioning from traditional to newer methods is the scarcity of academic and industrial experience with the latter. This literature review serves as a guide for the selection of analytical methods targeting quality attributes for rapid, high-throughput process characterization during process development of rAAV-mediated gene therapies. This review discusses analytical methods for the characterization of rAAV-based products during their development. With the focus on vector titer, content ratio, and aggregation, the review assesses established and upcoming methods and serves as a guide for the selection of analytical methods for rAAV development.
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影响因子：
4.7
作者：
Carvalho, Sofia B.;Moleirinho, Mafalda G.;Carrondo, Manuel J. T.
通讯作者：
Carrondo, Manuel J. T.
影响因子：
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作者：
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影响因子：
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DOI：
10.1016/b978-0-444-59573-7.00007-5
发表时间：
2015-01-01
期刊：
BIOPHYSICAL CHARACTERIZATION OF PROTEINS IN DEVELOPING BIOPHARMACEUTICALS
影响因子：
--
作者：
Berkowitz, Steven A.;Houde, Damian J.
通讯作者：
Houde, Damian J.
影响因子：
3.8
作者：
Barnard, James G.;Babcock, Ken;Carpenter, John F.
通讯作者：
Carpenter, John F.