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.

 
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