Martínez-Molina Eduardo, Chocarro-Wrona Carlos, Martínez-Moreno Daniel, Marchal Juan A, Boulaiz Houria
Biopathology and Medicine Regenerative Institute (IBIMER), University of Granada, 18016 Granada, Spain.
Department of Human Anatomy and Embryology, University of Granada, 18016 Granada, Spain.
Pharmaceutics. 2020 Nov 3;12(11):1051. doi: 10.3390/pharmaceutics12111051.
Lentiviral vectors (LVs) have gained value over recent years as gene carriers in gene therapy. These viral vectors are safer than what was previously being used for gene transfer and are capable of infecting both dividing and nondividing cells with a long-term expression. This characteristic makes LVs ideal for clinical research, as has been demonstrated with the approval of lentivirus-based gene therapies from the Food and Drug Administration and the European Agency for Medicine. A large number of functional lentiviral particles are required for clinical trials, and large-scale production has been challenging. Therefore, efforts are focused on solving the drawbacks associated with the production and purification of LVsunder current good manufacturing practice. In recent years, we have witnessed the development and optimization of new protocols, packaging cell lines, and culture devices that are very close to reaching the target production level. Here, we review the most recent, efficient, and promising methods for the clinical-scale production ofLVs.
近年来，慢病毒载体（LVs）作为基因治疗中的基因载体已获得重要价值。这些病毒载体比以前用于基因转移的载体更安全，并且能够感染分裂细胞和非分裂细胞并实现长期表达。这一特性使慢病毒载体成为临床研究的理想选择，美国食品药品监督管理局和欧洲药品管理局批准基于慢病毒的基因疗法就证明了这一点。临床试验需要大量功能性慢病毒颗粒，而大规模生产一直具有挑战性。因此，目前的工作重点是解决在现行药品生产质量管理规范下与慢病毒载体生产和纯化相关的缺点。近年来，我们见证了新方案、包装细胞系和培养设备的开发与优化，这些都已非常接近目标生产水平。在此，我们综述慢病毒载体临床规模生产的最新、高效且有前景的方法。
