Tumor-targeting synthetic adenoviruses and uses thereof
AssigneeThe Salk Institute for Biological Studies
InventorsClodagh O'Shea, Colin Powers, Lei Zhang
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Abstract
Synthetic adenoviruses with liver detargeting mutations and expressing an adenovirus type 34 (Ad34) fiber protein, or a chimeric fiber protein with an Ad34 knob domain, are described. The synthetic adenoviruses traffic to sites of tumors. Use of the synthetic adenoviruses for delivering diagnostic or therapeutic transgenes to tumors are also described.
Claims20
A method of expressing a transgene in tumor cells of a subject, comprising administering to the subject a synthetic adenovirus comprising:
- the transgene;
- a native or modified capsid that detargets the synthetic adenovirus from the liver;
- and
- an adenovirus type 34 (Ad34) fiber protein or a chimeric fiber protein comprising an adenovirus type 5 (Ad5) shaft domain and an Ad34 knob domain.
A method of diagnosing a subject as having a tumor, comprising administering to the subject a synthetic adenovirus comprising:
- a diagnostic transgene;
- a native or modified capsid that detargets the synthetic adenovirus from the liver;
- and
- an adenovirus type 34 (Ad34) fiber protein or a chimeric fiber protein comprising an adenovirus type 5 (Ad5) shaft domain and an Ad34 knob domain.
A method of treating a tumor in a subject, comprising administering to the subject a synthetic adenovirus comprising:
- a therapeutic transgene;
- a native or modified capsid that detargets the synthetic adenovirus from the liver;
- and
- an adenovirus type 34 (Ad34) fiber protein or a chimeric fiber protein comprising an adenovirus type 5 (Ad5) shaft domain and an Ad34 knob domain.
A synthetic adenovirus genome, comprising a nucleotide sequence at least 95% identical to SEQ ID NO:
- 2 or SEQ ID NO:
- 5.
Dependencies are inferred from the claim text.