Targeted UDP-glucose ceramide glucosyltransferase stable overexpression induces a metabolic switch improving cell performance at high cell density.

ABSTRACT:

Background

Viral vectors such as adeno-associated viruses (AAVs) and virus-like particles (VLPs) are critical tools in gene therapy, typically produced using transient gene expression (TGE). Intensification of TGE processes to high cell densities is hampered by the cell density effect (CDE), characterized by decreased cell-specific productivity as cell density increases. Physiological changes following transfection, particularly reduced glycosphingolipid biosynthesis, have been identified as factors affecting productivity and viability.

Methods

We used a targeted integration approach to generate HEK293SF-3F6 cell lines constitutively or inducibly overexpressing UDP-glucose ceramide glucosyltransferase (UGCG), the precursor enzyme responsible for glycosphingolipid biosynthesi

SUBMITTER: Rahimi M 

PROVIDER: S-EPMC12556263 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature