NEUTRALIZATION OF ENDOGENOUS INTERFERON-BETA INCREASES THE EFFICIENCYOF ADENOVIRAL VECTOR-MEDIATED GENE TRANSDUCTION

One reason for low transduction efficiency and, hence, the inefficienc y of gene therapy using adenoviral vectors may be the natural antivira l defense mechanisms of hosts, In this study, we investigated the effe cts of endogenous interferon-beta (IFN-beta) on gene transduction by a denoviral vectors, Infection of murine macrophages with Ad5CMV-LacZ pr oduced increased expression of endogenous IFN-beta, Neutralization wit h anti-IFN-beta antibody (but not control immunoglobulin) during infec tion with the vector enhanced expression of LacZ, In contrast, IFN-bet a gene expression was not detected in readily transduced NIH 3T3 cells , and the transduction efficiency of NIH 3T3 cells was unaffected by t he antibody, LacZ gene expression in NIH 3T3 cells was decreased when cocultured with macrophages or in the presence of exogenous IFN-beta. The addition of the anti-IFN-beta antibody reversed this inhibition, T hese results demonstrate that IFN-beta-mediated cellular antiviral mec hanisms are a barrier to gene transduction by adenoviral vectors.