The application of adenoviral vectors in @entity5 gene therapy is hampered by low receptor expression on @entity5 cells and high receptor expression on normal epithelial cells. Targeting adenoviral vectors toward @entity5 cells may improve @entity5 gene therapy procedures by providing augmented @entity5 transduction and decreased @entity137 to normal tissues. Targeting requires both the complete abolition of native tropism and the addition of a new specific binding ligand onto the viral capsid. Here we accomplished this by using doubly ablated adenoviral vectors, lacking coxsackievirus-adenovirus receptor and alpha(v) integrin binding capacities, together with bispecific single-chain antibodies targeted toward @entity1 @entity470 ( @entity470 ) or the epithelial cell adhesion molecule. These vectors efficiently and selectively targeted both alternative receptors on the surface of @entity1 @entity5 cells. Targeted doubly ablated adenoviral vectors were also very efficient and specific with primary @entity1 @entity5 specimens. With primary @entity11 cell cultures, @entity470 targeting augmented the median gene transfer efficiency of doubly ablated adenoviral vectors 123-fold. Moreover, @entity470 -targeted doubly ablated vectors were selective for @entity1 @entity1313 versus the surrounding normal brain tissue. They transduced organotypic @entity11 and @entity1653 spheroids with efficiencies similar to those of native adenoviral vectors, while exhibiting greater-than-10-fold-reduced background levels on normal brain explants from the same @entity1 . As a result, @entity470 -targeted doubly ablated adenoviral vectors had a 5- to 38-fold-improved @entity5 -to-normal brain targeting index compared to native vectors. Hence, single-chain targeted doubly ablated adenoviral vectors are promising tools for @entity5 gene therapy. They should provide an improved therapeutic index with efficient @entity5 transduction and effective protection of normal tissue.

Efficient and selective gene transfer into primary @entity1 XXXX by using single-chain antibody-targeted adenoviral vectors with native tropism abolished.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity1313 :: ('MESH:D001932', 'Disease') :: ['brain tumors'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity470 :: ('1956', 'Gene') :: ['EGFR', 'epidermal growth factor receptor'] @entity11 :: ('MESH:D005910', 'Disease') :: ['glioma'] @entity1653 :: ('MESH:D008579', 'Disease') :: ['meningioma']
@entity1313 :: (MESH:D001932,Disease) :: ['brain tumors']
