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Gene Transfer to Brain and Spinal Cord Using Recombinant Adenoviral Vectors

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Recombinant adenoviral (Ad) vectors are derived from human adenoviruses: nonenveloped, encapsidated linear, double-stranded DNA viruses that commonly cause respiratory and gastrointestinal infections. Forty-three different human adenovirus serotypes have been characterized (1 ). Details about production of recombinant Ad vectors are given in Chapter 1 . Ad vectors in widespread use are derived from human Ad serotypes 2 and 5 (Ad2 and Ad5), Ad5 being more common for applications in the central nervous system (CNS). Ad5 replication-impaired vectors most often contain deletions in the E1 and E3 regions, with transgenes driven by a variety of promoters including viral promoters, and those that are neuron-specific (2 ). Recently fiber-modified and “gutless” Ad vectors, and those based on canine adenovirus serotype 2, have been developed for use in brain (3 9 ).
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