title: In vitro selection of viral vectors with modified tropism: the adeno-associated virus display.
abstract: Improving the efficiency and specificity of gene vectors is critical for the success of gene therapy. In an effort to generate viral mutants with controlled tropism we produced a library of adeno-associated virus (AAV) clones with randomly modified capsids and used it for the selection of receptor-targeting mutants. After several rounds of selection on different cell lines that were resistant to infection by wild-type (wt) AAV, infectious mutants were harvested at high titers. These mutants transduced target cells with an up to 100-fold increased efficiency, in a receptor-specific manner and without interacting with the primary receptor for wt AAV. The results demonstrate for the first time that a combinatorial approach based on a eukaryotic virus library allows one to generate efficient, receptor-specific targeting vectors with desired tropism.
authors.affiliation: Genzentrum, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377, Munich, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Perabo
authors.forename: Hildegard
authors.initials: H
authors.lastname: Büning
authors.forename: David M
authors.initials: DM
authors.lastname: Kofler
authors.forename: Martin U
authors.initials: MU
authors.lastname: Ried
authors.forename: Anne
authors.initials: A
authors.lastname: Girod
authors.forename: Clemens M
authors.initials: CM
authors.lastname: Wendtner
authors.forename: Jörg
authors.initials: J
authors.lastname: Enssle
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
mesh_terms: D001483:Base Sequence; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D000229:Dependovirus / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015723:Gene Library; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000032:analysis*; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D014161:Transduction, Genetic; D018523:Tropism