The successful prophylactic treatment of @entity447 by frequent infusions of plasma concentrates or recombinant @entity15105 ( @entity2801 ) indicates that gene therapy may be a potential alternative for the treatment of the disease. For efficient delivery and long-term expression of the @entity2801 gene, a novel minimal adenovirus (mini-Ad) vector, MiniAdFVIII, has been developed. The vector is devoid of all viral genes and carries the full-length @entity2801 cDNA under the control of the @entity1 12.5-kb albumin promoter. The MiniAdFVIII vector was propagated with the assistance of an ancillary vector in 293 cells and was purified by @entity6928 banding. Sustained expression of @entity2801 at physiologic levels (100-800 ng/mL) was achieved in @entity19 after a single intravenous injection of MiniAdFVIII. The expressed @entity2801 had a structure identical to that of recombinant @entity2801 , as determined by Western blot analysis. The functionality of the protein was confirmed by the restoration of @entity1003 capacity in MiniAdFVIII-treated hemophilic @entity19 , as determined by tail clipping observations. Although antivector or antihuman @entity15105 antibodies at various levels were detected, long-term expression of the transgene was observed in the @entity19 that did not generate antibodies against the transgene product. The vector DNA persisted in the liver tissues of the @entity19 with long-term expression. No significant histopathologic findings or @entity137 were observed to be associated with the vector in the MiniAdFVIII-treated C57BL/6 @entity19 . These results support the further development of MiniAdFVIII for clinical trials toward the treatment of @entity447 .

Sustained high-level expression of full-length XXXX factor VIII and restoration of clotting activity in hemophilic @entity19 using a minimal adenovirus vector.

@entity2801 :: ('2157', 'Gene') :: ['hFVIII'] @entity1 :: ('9606', 'Species') :: ['human'] @entity15105 :: ('14069(Tax:10090)', 'Gene') :: ['FVIII', 'factor VIII'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity447 :: ('MESH:D006467', 'Disease') :: ['hemophilia A'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1003 :: ('MESH:D001778', 'Disease') :: ['blood coagulation'] @entity6928 :: ('MESH:C028019', 'Chemical') :: ['CsCl']
@entity1 :: (9606,Species) :: ['human']
