Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses

A method for generating a chimeric adenovirus for production in a selected host cell, said chimeric adenovirus derived from a parental adenovirus which is not useful for adenovirus virion production in the host cell type, said method comprising the step of generating a chimeric adenovirus comprising:

• 5′ and 3′ terminal regions of a first adenovirus which grows in a selected host cell type, said 5′ terminal regions comprising the 5′ inverted terminal repeat (ITRs) and necessary E1 gene functions, and said 3′ terminal regions comprising inverted terminal repeat (ITRs) and necessary E4 gene functions;
• and
• internal regions from the parental adenovirus, said internal regions comprising the hexon, penton base and fiber and lacking at least its native 5′ and 3′ terminal regions;
• wherein the resulting chimeric adenovirus comprises, from 5′ to 3′, the 5′ terminal region of the first adenovirus, the internal region of the parental adenovirus, and the 3′ terminal regions of the first adenovirus.

A chimeric adenovirus comprising a hexon protein of a selected adenovirus serotype, said chimeric adenovirus derived from a parental adenovirus which is not useful for adenovirus virion production in a selected host cell type, said chimeric adenovirus comprising:

• (a) adenovirus sequences of the left terminal end of a first adenovirus which grows in the selected host cell type, said left end region comprising the E1a, E1b and 5′ inverted terminal repeat (ITRs);
• (b) adenovirus sequences of the internal region of the selected parental adenovirus, said internal region comprising the genes encoding the penton, hexon and fiber of the selected adenovirus;
• (c) adenovirus sequences of the right terminal end of the first adenovirus, said right end region comprising the necessary E4 gene functions and the 3′ inverted terminal repeat (ITRs),
• wherein the resulting chimeric adenovirus comprises adenoviral structural and regulatory proteins necessary for infection and replication.