{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["32(1)"],"submitter":["Stibbs DJ"],"funding":["UKRI"],"pubmed_abstract":["Continuous manufacturing of lentiviral vectors (LVs) using stable producer cell lines could extend production periods, improve batch-to-batch reproducibility, and eliminate costly plasmid DNA and transfection reagents. A continuous process was established by expanding cells constitutively expressing third-generation LVs in the iCELLis Nano fixed-bed bioreactor. Fixed-bed bioreactors provide scalable expansion of adherent cells and enable a straightforward transition from traditional surface-based culture vessels. At 0.5 vessel volume per day (VVD), the short half-life of LVs resulted in a low total infectious titer at 1.36 × 10<sup>4</sup> TU cm<sup>-2</sup>. Higher perfusion rates increased titers, peaking at 7.87 × 10<sup>4</sup> TU cm<sup>-2</sup> at 1.5 VVD. The supernatant at 0.5 VVD had a physical-to-infectious particle ratio of 659, whereas this was 166 ± 15 at 1, 1.5, and 2 VVD. Reducing the pH from 7.20 to 6.85 at 1.5 VVD improved the total infectious yield to 9.10 × 10<sup>4</sup> TU cm<sup>-2</sup>. Three independent runs at 1.5 VVD and a culture pH of 6.85 showed low batch-to-batch variability, with a coefficient of variation of 6.4% and 10.0% for total infectious and physical LV yield, respectively. This study demonstrated the manufacture of high-quality LV supernatant using a stable producer cell line that does not require induction."],"journal":["Molecular therapy. Methods & clinical development"],"pagination":["101209"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10907162"],"repository":["biostudies-literature"],"pubmed_title":["Continuous manufacturing of lentiviral vectors using a stable producer cell line in a fixed-bed bioreactor."],"pmcid":["PMC10907162"],"pubmed_authors":["Stibbs DJ","Jackson NB","Silva Couto P","Rafiq QA","Takeuchi Y","Rayat ACME"],"additional_accession":[]},"is_claimable":false,"name":"Continuous manufacturing of lentiviral vectors using a stable producer cell line in a fixed-bed bioreactor.","description":"Continuous manufacturing of lentiviral vectors (LVs) using stable producer cell lines could extend production periods, improve batch-to-batch reproducibility, and eliminate costly plasmid DNA and transfection reagents. A continuous process was established by expanding cells constitutively expressing third-generation LVs in the iCELLis Nano fixed-bed bioreactor. Fixed-bed bioreactors provide scalable expansion of adherent cells and enable a straightforward transition from traditional surface-based culture vessels. At 0.5 vessel volume per day (VVD), the short half-life of LVs resulted in a low total infectious titer at 1.36 × 10<sup>4</sup> TU cm<sup>-2</sup>. Higher perfusion rates increased titers, peaking at 7.87 × 10<sup>4</sup> TU cm<sup>-2</sup> at 1.5 VVD. The supernatant at 0.5 VVD had a physical-to-infectious particle ratio of 659, whereas this was 166 ± 15 at 1, 1.5, and 2 VVD. Reducing the pH from 7.20 to 6.85 at 1.5 VVD improved the total infectious yield to 9.10 × 10<sup>4</sup> TU cm<sup>-2</sup>. Three independent runs at 1.5 VVD and a culture pH of 6.85 showed low batch-to-batch variability, with a coefficient of variation of 6.4% and 10.0% for total infectious and physical LV yield, respectively. This study demonstrated the manufacture of high-quality LV supernatant using a stable producer cell line that does not require induction.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-08T06:10:55.396Z","creation":"2025-04-07T04:44:30.397Z"},"accession":"S-EPMC10907162","cross_references":{"pubmed":["38435128"],"doi":["10.1016/j.omtm.2024.101209"]}}