Production of Lentiviral Vectors Using a HEK-293 Producer Cell Line and Advanced Perfusion Processing

• DOI: 10.3389/fbioe.2022.887716
• Publication Date: 2022-06-14T11:44:06Z
• Authors: Michelle Yen Tran; Amine A. Kamen
• Keywords: HEK 293 cells; Line (geometry)

The field of lentiviral vector (LV) production continues to face challenges in large-scale manufacturing, specifically regarding producing enough vectors meet the demand for treating patients as well high and consistent quality efficient dosing. Two areas interest are use stable producer cell lines, which facilitates scalability LV processes making process more reproducible robust clinical applications, search a retention device scalable industrial-size bioreactors. This manuscript investigates line LVs with GFP transgene at shake flask scale demonstrates 3L bioreactor using Tangential Flow Depth Filtration (TFDF) perfusion mode. Cumulative functional yields 3.3 x 1011 3.9 transducing units were achieved; former over 6 days 16.3 L perfused media latter 4 16 L. In comparing previously published value that was achieved same acoustic filter scale, TFDF run produced 1.5-fold higher cumulative yield. Given its scale-up potential, is an excellent candidate be further evaluated determine optimized conditions can ultimately support continuous manufacturing large scale.