EMERGENCE OF EARLY REGION-1-CONTAINING REPLICATION-COMPETENT ADENOVIRUS IN STOCKS OF REPLICATION-DEFECTIVE ADENOVIRUS RECOMBINANTS (DELTA-E1 PLUS DELTA-E3) DURING MULTIPLE PASSAGES IN 293-CELLS

Early region 1 (E1)-deleted-human adenovirus (AV) recombinants have be en shown to be powerful tools of gene transfer in vivo and in vitro an d are considered for application in human gene therapy, We could detec t increasing titers of E1-containing adenovirus in two independent E1E3-deleted recombinant AV stocks during multiple passages in 293 cells , most likely due to a recombination event with the host cell genome. We show the deleterious effects of this E1-containing, mostly replicat ion-competent AV subpopulation in vivo and compare different screening methods of AV stocks for its detection, These considerations are impo rtant for the safety of human gene therapy trials.