iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2780-901, Portugal; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. Da República, Oeiras, 2780-157, Portugal.
SANOFI, 49 New York Avenue, Framingham, MA 01701, USA.
Curr Opin Biotechnol. 2022 Apr;74:271-277. doi: 10.1016/j.copbio.2021.12.009. Epub 2022 Jan 7.
Recombinant adeno-associated (rAAV) vector-based gene therapy has been the focus of intense research driven by the safety profile and several recent clinical breakthroughs. As of April 2021, there are two rAAV-based gene therapies approved and more than two-hundred active clinical trials (approximately thirty in Phase III). However, the expected increase in demand for rAAV vectors still poses several challenges. Discussed herein are key aspects related to R&D needs and Chemistry, Manufacturing and Control (CMC) efforts required to attend this growing demand. Authors provide their perspective on strategic topics for rAAV-based therapies success: scalability and productivity; improved safety; increased process understanding combined with development of orthogonal bioanalytics that are able to identify, monitor and control Critical Quality Attributes (CQAs) during bioprocessing.
基于重组腺相关（rAAV）载体的基因治疗一直是研究的焦点，其安全性特征和最近的一些临床突破推动了这一研究。截至 2021 年 4 月，已有两种基于 rAAV 的基因疗法获得批准，还有两百多项活跃的临床试验（约有三十项处于第三阶段）。然而，rAAV 载体需求的预期增长仍然带来了一些挑战。本文讨论了与研发需求以及化学、制造和控制（CMC）工作相关的关键方面，以满足这一不断增长的需求。作者提供了他们对 rAAV 为基础的治疗成功的战略主题的看法：可扩展性和生产力；提高安全性；在生物工艺过程中，通过开发能够识别、监测和控制关键质量属性（CQAs）的正交生物分析方法，提高过程理解。
