Infectivity-enhanced conditionally-replicative adenovirus and uses thereof
OwnerDavid T. Curiel, Victor Krasnykh +2inventors
InventorsDavid T. Curiel, Victor Krasnykh, Ramon Alemany, Igor Dmitriev
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Abstract
A modified adenovirus capable of overcoming the problem of low level of coxsackie-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to specific promoter control or mutations in E1a or E1b genes.
Claims24
An infectivity-enhanced conditionally-replicative adenovirus, wherein said adenovirus possesses enhanced infectivity towards a specific cell type due to a modification or replacement of the fiber of a wildtype adenovirus, said modification or replacement results in enhanced infectivity relative to said wildtype adenovirus, and wherein said infectivity-enhanced conditionally-replicative adenovirus has at least one conditionally regulated early gene, said early gene conditionally regulated such that replication of said infectivity-enhanced conditionally-replicative adenovirus is limited to said specific cell type.
A method of providing adenoviral gene therapy in an individual, comprising the steps of:
- administering to said individual a therapeutic dose of an infectivity-enhanced conditionally-replicative adenovirus, wherein said adenovirus possesses enhanced infectivity towards a specific cell type due to modification or replacement of the fiber of a wildtype adenovirus, wherein said modification or replacement results in enhanced infectivity relative to said wildtype adenovirus, and wherein said infectivity-enhanced conditionally-replicative adenovirus has at least one conditionally regulated early gene, said early gene conditionally regulated such that replication of said infectivity-enhanced conditionally-replicative adenovirus is limited to said specific cell type.
Dependencies are inferred from the claim text.