Preventing spontaneous genetic rearrangements in the transgene cassettes of adenovirus vectors.

ABSTRACT: First-generation, E1/E3-deleted adenoviral vectors with diverse transgenes are produced routinely in laboratories worldwide for development of novel prophylactics and therapies for a variety of applications, including candidate vaccines against important infectious diseases, such as HIV/AIDS, tuberculosis, and malaria. Here, we show, for two different transgenes (both encoding malarial antigens) inserted at the E1 locus, that rare viruses containing a transgene-inactivating mutation exhibit a selective growth advantage during propagation in E1-complementing HEK293 cells, such that they rapidly become the major or sole species in the viral population. For one of these transgenes, we demonstrate that viral yield and cytopathic effect are enhanced by repression of transgene expression in the

SUBMITTER: Cottingham MG 

PROVIDER: S-EPMC4981243 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature