A major goal in gene therapy is to develop efficient gene transfer protocols that allow tissue-specific, long-term and tightly regulated expression of the desired transgene. This objective is becoming more attainable through the co-evolution of gene transfer vectors and regulation systems. The ideal vector should efficiently transduce non-dividing cells with minimal @entity137 , thus endowing the system with persistent transgene expression. The helper-dependent adenovirus vectors meet these requirements, as demonstrated in various studies in the literature. The most promising regulation system is the tet-on system, which has low basal transcriptional activity and high inducibility. To explore the regulated transgene expression in the context of a helper-dependent vector, we constructed the @entity2033 -TET-IFN vector, containing the mIFN(alpha) gene under the control of the @entity803 inducible transactivator rtTA2(s)-S2. @entity19 injected with @entity2033 -TET-IFN showed high levels of serum mIFN(alpha) only upon transcriptional activation. The transgene expression was reinducible to the same high level up to 3 months p.i., and the amount of expressed cytokine could be regulated by dosing @entity3403 . Transcriptional activation of mIFN(alpha) induced by @entity3403 resulted in prolonged survival and reduced @entity409 in @entity2033 -TET-IFN-injected @entity19 challenged with a lethal dose of coronavirus. Activation of antiviral genes mediated by @entity3403 -dependent mIFN(alpha) expression was also observed at low @entity2033 -TET-IFN doses. The possibility of controlling gene expression by the combination of @entity2033 vectors and the latest tet-on transactivator also holds promise for studying gene function in other animal models.

Regulated and prolonged expression of mIFN(alpha) in immunocompetent XXXX mediated by a helper-dependent adenovirus vector.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity3403 :: ('MESH:D004318', 'Chemical') :: ['doxycycline'] @entity409 :: ('MESH:D008107', 'Disease') :: ['liver damage'] @entity2033 :: ('MESH:D006816', 'Disease') :: ['HD'] @entity803 :: ('MESH:D013752', 'Chemical') :: ['tetracycline']
@entity19 :: (10090,Species) :: ['mice']
