MEANS AND METHODS TO INCREASE ADENOVIRUS PRODUCTION

摘要

The invention relates in a first embodiment to a method for increasing the yield of replication-incompetent adenoviruses having at least a partial deletion in the E1-region, wherein said adenoviruses are generated in a production cell, the method comprising the steps of: (a) expressing in said production cell an adenoviral pIX polypeptide from a nucleic acid sequence encoding said adenoviral pIX polypeptide under the control of (i) at least a minimal endogenous pIX promoter and a heterologous promoter; or (ii) a heterologous promoter; and (b) expressing in said production cell the elements necessary for the production and assembly of said adenoviruses from corresponding coding sequences, thereby increasing the yield of said adenoviruses generated in said production cell in comparison to the yield of replication-incompetent adenoviruses having at least a partial deletion in the E1-region generated in said production cell in the absence of said nucleic acid sequence encoding said adenoviral pIX polypeptide. In another embodiment, the invention relates to a method for constructing an adenovirus library, a production cell as well as the use of an adenoviral pIX polypeptide for increasing the yield of replication-incompetent adenoviruses having at least a partial deletion in the E1-region.

主权项

1. A method for increasing the yield of replication-incompetent adenoviruses having at least a partial deletion in the E1-region, wherein said adenoviruses are generated in a production cell, the method comprising the steps of:
(a) expressing in said production cell an adenoviral pIX polypeptide from a nucleic acid sequence encoding said adenoviral pIX polypeptide under the control of
(i) at least a minimal endogenous pIX promoter and a heterologous promoter; or(ii) a heterologous promoter; and (b) expressing in said production cell the elements necessary for the production
and assembly of said adenoviruses from corresponding coding sequences, thereby increasing the yield of said adenoviruses generated in said production cell in comparison to the yield of replication-incompetent adenoviruses having at least a partial deletion in the E1-region generated in said production cell in the absence of said nucleic acid sequence encoding said adenoviral pIX polypeptide.