Development of Novel El-Complementary Cells for Adenoviral Production Free of Replication-Competent Adenovirus

摘要

Human adenoviruses have been used as highly efficient gene delivery vehicles or oncolytic agents in a variety of clinical and preclinical studies. Recombinant adenoviruses have predominantly been rendered replication defective or conditionally replicating via modifications to the El region, such as deletions, mutations, or replacement of the endogenous transcriptional control elements . However, the El gene products are important for directing cellular and viral gene expression to enable a productive virus life cycle. During viral infection, E1A expression pushes the cell cycle into S phase to support viral DNA replication and E1B expression delays cellular apoptosis, thus gaining time for successful viral production . Therefore, due to the essential role of El genes in adenoviral biology, the helper-independent production of El-modified adenoviral vectors is assisted by cell lines that produce complementary El proteins.