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US 7,094,398 B1Granted
Recombinant adenoviral vectors expressing chimeric fiber proteins for cell specific infection and genome integration
AssigneeUniversity of Washington
InventorsAndré Lieber, Dmitry M Shayakhmetov, Denise R Farrer, Thalia Papayannopoulou, George Stamatoyannopoulos
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Abstract
The present invention provides for novel chimeric Ad-vectors carrying transgene, or portions of transgenes for stable and efficient gene transfer into diverse cell types or tissues in a CAR- and/or αυβ3/5-independent manner. Also provided are methods for producing such vectors and the use thereof for gene therapy to target a specific cell type or tissue.
Claims25
A recombinant, double-stranded, adenovirus vector, wherein the vector comprises:
- a. an adenovirus left inverted terminal repeat sequence;
- b. an adenovirus packaging sequence;
- c. a first adenoviral-associated inverted terminal repeat sequence;
- d. a first inverted repeat sequence;
- e. a heterologous promoter sequence which mediates transcription in a direction towards the adenoviral left inverted terminal repeat sequence in part a;
- f. a foreign gene sequence;
- g. a second inverted repeat sequence;
- h. a second adenoviral-associated inverted terminal repeat sequence;
- i. a gene sequence that mediates replication of an adenovirus in a transduced cell;
- and
- j. an adenovirus right inverted terminal repeat sequence;
- wherein the adenovirus packaging sequence is located on the one strand of the double-stranded vector;
- and wherein the other of the two strands of the double-stranded vector comprises a nucleotide sequence encoding a modified adenoviral fiber protein which alters the tropism of the adenovirus vector, and
- wherein the modified adenoviral fiber protein is a modified fiber knob, a modified fiber tail or a modified fiber shaft.
11 more elements
A recombinant, double-stranded, adenovirus vector wherein the vector comprises:
- a. an adenovirus left inverted terminal repeat sequence;
- b. an adenovirus packaging sequence;
- c. a first adenoviral-associated inverted terminal repeat sequence;
- d. a first inverted repeat sequence;
- e. a heterologous promoter sequence which mediates transcription in a direction away from the adenoviral left inverted terminal repeat sequence in part a;
- f. a foreign gene sequence;
- g. a second inverted repeat sequence;
- h. a second adenoviral-associated inverted terminal repeat sequence;
- i. a gene sequence that mediates replication of an adenovirus in a transduced cell;
- and
- j. an adenovirus right inverted terminal repeat sequence;
- wherein the adenovirus packaging sequence is located on one strand of the double-stranded vector of the vector;
- and wherein the other of the two strands of the double-stranded vector comprises a nucleotide sequence encoding a modified adenoviral fiber protein which alters the tropism of the adenovirus vector, and wherein the modified adenoviral fiber protein is a modified fiber knob, a modified fiber tail or a modified fiber shaft.
10 more elements
Dependencies are inferred from the claim text.