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Adenovirus (Ad) vectors provide a highly efficient means of mammalian gene transfer and are widely used for high-level protein expression in mammalian cells, as recombinant vaccines and for gene therapy. A commonly used method for constructing Ad vectors relies on in vivo homologous recombination between two Ad DNA-containing bacterial plasmids(More)
Helper-dependent (HD) adenoviral vectors devoid of all viral coding sequences have a large cloning capacity and have been reported to provide long-term transgene expression in vivo with negligible toxicity, making them attractive vectors for gene therapy. Currently, the most efficient means of generating HD vectors involves co-infecting 293 cells expressing(More)
We have evaluated the potential of liver-directed, helper-dependent adenoviral (HDAd) vector-mediated gene therapy in the hemophilia B dog. Two dogs were injected intravenously with HDAd (3 x 10(12) VP/kg) bearing a liver-restricted canine coagulation factor IX (FIX) expression cassette. After injection, the whole blood clotting time for both dogs declined(More)
Helper-dependent adenoviral vectors possess a number of characteristics that make them attractive gene therapy vectors. These vectors are completely devoid of viral coding sequences and are able to mediate high-efficiency transduction in vivo to direct sustain high-level transgene expression with negligible chronic toxicity. This review focuses on advances(More)
Helper-dependent adenoviral vectors (HDAds) are devoid of all viral coding sequences and have demonstrated tremendous potential for gene therapy by providing increased cloning capacity (up to 37 kb) and long-term, high-level transgene expression in vivo with negligible toxicity. Currently, the most widely used method of producing HDAds is the Cre/loxP(More)
Adenoviruses are robust gene delivery vectors in vivo, but are limited by their propensity to provoke strong innate and adaptive responses. Previous work has demonstrated that polyethylene glycol (PEG) modification of adenovirus can protect the vectors from preexisting and adaptive immune responses by reducing protein-protein interactions. To test whether(More)
The two-plasmid rescue method of constructing Ad vectors, which relies on either homologous or Cre-mediated recombination between two plasmids cotransfected into 293 or 293Cre4 cells, respectively, offers advantages over other approaches because of its simplicity. We have improved the efficiency of vector construction by both homologous and Cre-mediated(More)
We have recently developed a high-efficiency method of constructing adenovirus vectors based on Cre-mediated recombination between two plasmids co-transfected into 293 cells. The simplicity and efficiency of this method should greatly expedite the construction of most recombinant vectors. However, this system would not be suitable for constructing vectors(More)
Broad, multispecific CD4(+) and CD8(+) T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of these responses in an ideal vaccine(More)