Means and methods to increase adenovirus production

A method for the construction of a replication-incompetent adenovirus library, wherein the adenoviruses have at least a partial deletion in the E1-region, comprising the steps of:

• (a) providing one or more nucleic acid sequences in expressible form comprising at least two partial adenoviral genomes, wherein each nucleic acid sequence of said one or more nucleic acid sequences comprises at least one partial adenoviral genome, each partial adenoviral genome further comprising at least one transgene, wherein the at least two partial adenovirus genomes and/or the two transgenes differ from each other;
• (b) introducing the one or more nucleic acid sequences of step (a) into production cells comprising one or more nucleic acid sequences in expressible form comprising a partial adenoviral genome which complements each partial adenoviral genome comprised by the one or more nucleic acid sequences of step (a) by transfection, wherein each complemented adenoviral genome encodes the elements necessary for the production and assembly of said different adenoviruses and comprises the coding sequence for an adenoviral pIX polypeptide under the control of at least a minimal endogenous pIX promoter and a heterologous promoter, wherein said minimal endogenous pIX promoter is located downstream of said heterologous promoter;
• and
• (c) culturing the production cells under conditions suitable for the assembly and production of said differing adenoviruses,
• thereby constructing said replication-incompetent adenovirus library.