Oncolytic adenovirus compositions
AssigneeThe Salk Institute for Biological Studies
InventorsClodagh O'Shea, Shigeki Miyake-Stoner
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Abstract
An adenovirus comprising an E1A polypeptide comprising one or more modifications and comprising an E4orf6/7 polypeptide comprising one or more modifications is described. Compositions and kits comprising the modified adenoviruses are also described. Further described is a method of treating a proliferative disorder in a subject comprising administering to the subject an adenovirus comprising the E1A polypeptide comprising one or more modifications and comprising the E4orf6/7 polypeptide comprising one or more modifications.
Claims26
A recombinant adenovirus comprising:
- a modified genome comprising:
- (i) an adenovirus E1A promoter operably linked to a nucleic acid sequence encoding an E1A protein comprising a modification in a first Rb-binding site;
- and
- (ii) an adenovirus E4 promoter operably linked to an E4orf6/7 gene product coding sequence having a deletion or a modification of only one of the two E4orf6/7 exons, wherein the deletion of the modification impairs E4orf6/7 gene product activity and/or expression;
- wherein the recombinant adenovirus selectively replicates in Rb-deficient cells.
A recombinant adenovirus comprising:
- (i) an adenovirus E1A promoter operably linked to a nucleic acid sequence encoding an E1A protein comprising a modification in a first Rb-binding site;
- and
- (ii) an adenovirus E4 promoter operably linked to an E4orf6/7 gene product coding sequence having a deletion or a modification of only one of the two E4orf6/7 exons, wherein the deletion or the modification impairs E4orf6/7 gene product activity and/or expression;
- and
- (ii) a nucleic acid sequence encoding an E4orf1 protein comprising one or more modifications;
- or a deletion of all of the E4orf1 coding sequence;
- wherein the recombinant adenovirus selectively replicates in Rb-deficient cells.
Dependencies are inferred from the claim text.