presented are ways to address the problem of replication competent adenovirus in adenoviral production for use with , for example , gene therapy . packaging cells having no overlapping sequences with a selected vector and are suited for large scale production of recombinant adenoviruses . a method of the invention produces adenovirus incapable of replicating . the method includes a primary cell containing a nucleic acid based on or derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell . the isolated recombinant nucleic acid molecule is based on or derived from an adenovirus , and further has at least one functional encapsidating signal , and at least one functional inverted terminal repeat . the isolated recombinant nucleic acid molecule lacks overlapping sequences with the nucleic acid of the cell . otherwise , the overlapping sequences would enable homologous recombination leading to replication competent adenovirus in the primary cell into which the isolated recombinant nucleic acid molecule is to be transferred .