A PACKAGING CELL-LINE FOR PROPAGATION OF RECOMBINANT ADENOVIRUS VECTORS CONTAINING 2 LETHAL GENE-REGION DELETION

A cell line that provides the E1 as well as the E4 gene functions of h uman adenovirus 5 has been established by introduction of the full-len gth Ad5 E4 region into 293 cells. To avoid the E1A transactivation of the E4 gene expression, the E4 promoter was replaced by the mouse alph a inhibin promoter containing a cAMP response element. This cell line was used to generate E1/E4-deleted adenovirus vectors containing a lac Z gene in the E1 region under the control of mouse pgk promoter. The t iter and the lacZ gene expression of E1/E4-deleted adenovirus vector w ere comparable to those of E1-deleted vectors. Evidence of cytopathic effect was absent following infection of nonpermissive cell lines with E1/E4-deleted adenovirus in vitro. Establishment of the 293-E4 cell l ine and the generation of E1/E4-deleted adenovirus vectors may prolong gene expression in vivo and significantly improve the safety of adeno virus vectors for human gene therapy.