The present invention relates to recombinant Adenoviruses (Ad) which
function as helper viruses to gutted Ad viruses lacking viral coding
sequences. The recombinant Ad of the present invention comprise a binding
site of the E. coli Lac repressor protein embedded within the packaging
domain. Available Lac repressor protein binds to its operator site within
the helper virus packaging domain, precluding the binding of natural
packaging factors. The present invention also provides recombinant Ad
which in addition to having a binding site for the Lac repressor protein
within the packaging domain, also comprise coding sequence for the Lac
repressor protein under the control of a promoter which functions in
producer cells. Methods for suppressing packaging of helper Ad during
packaging of a gutted Ad vector are also provided as are methods of
producing recombinant helper Ad using lactose or lactose derivative as a
regulatory molecule. Temperature shift may also be used to regulate
growth of a recombinant helper Ad. In addition, methods of producing a
gutted Ad vector substantially free of helper Ad are provided.