摘要 |
Provided are methods of modulating the persistence of the expression in a ce ll of a transgene, such as a transgene in a non-Herpes vector or in at least E4.DELTA. adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gen e encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (i i) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or th e system further comprises a vector, in which case the vector comprises the transgene. Another method comprises contacting the cell with an at least E4.DELTA. adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, wherein the trans-acting factor modulates th e persistence of expression of the transgene and the gene encoding the trans- acting factor is not from the E4 region of an adenovirus. Yet another method comprises contacting a cell simultaneously or sequentially with (i) an at least E4.DELTA. adenoviral vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from t he E4 region of an adenovirus and which modulates the persistence of expression of the transgene. Also provided is a system for modulating the persistence o f expression of a transgene in an at least E4.DELTA. adenoviral vector, which system comprises (i) an at least E4.DELTA. adenoviral vector comprising a transgene and (ii) a gene encoding a trans-acting factor, wherein the gene encoding the trans-acting factor is not from the E4 region of an adenovirus, the trans-acting factor modulates the persistence of expression of the transgene, and either the at least E4.DELTA. adenoviral vector comprises the gene encoding the trans-acting factor or the system comprises a viral vector , in which case the viral vector comprises the gene encoding the trans-acting factor.
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