Synthetic adenoviruses with tropism to damaged tissue for use in promoting wound repair and tissue regeneration
AssigneeThe Salk Institute for Biological Studies
InventorsClodagh O'Shea, Colin Powers, Lei Zhang
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Abstract
Synthetic adenoviruses having chimeric fiber proteins and liver detargeting mutations are described. The synthetic adenovirus vectors are capable of specifically infecting cells at wound sites or in regions of damaged tissue. The synthetic adenovirus vectors also are capable of expressing transgenes, such as wound healing factors, at sites of wounded or damaged tissue. Accordingly, the described vectors can be used to detect wounded or damaged tissue, and/or to promote wound healing and regeneration of damaged tissue, such as by expression of heterologous wound healing or tissue regeneration factors.
Claims11
A method of promoting wound repair or tissue regeneration in a subject, comprising administering to the subject a synthetic adenovirus comprising:
- a transgene encoding platelet-derived growth factor-β(PDGF-β), transforming growth factor (TGF)-β1, or TGF-β2;
- a modified hexon protein comprising an E451Q mutation, numbered with reference to SEQ ID NO:
- 8;
- and
- a chimeric fiber protein comprising an adenovirus type 5 (Ad5) shaft domain and an adenovirus type 34 (Ad34) knob domain.
A method of promoting wound repair or tissue regeneration in a subject, comprising administering to the subject a synthetic adenovirus comprising:
- a transgene encoding platelet-derived growth factor-β(PDGF-β);
- a modified hexon protein comprising an E451Q mutation, numbered with reference to SEQ ID NO:
- 8;
- a deletion of the E1 region;
- one or more binding sites for liver-specific microRNA (miR)-122;
- and
- a chimeric fiber protein comprising an adenovirus type 5 (Ad5) shaft domain and an adenovirus type 34 (Ad34) knob domain.
Dependencies are inferred from the claim text.