title: Engineering the AAV capsid to optimize vector-host-interactions.
abstract: Adeno-associated viral (AAV) vectors are the most widely used delivery system for in vivo gene therapy. Vectors developed from natural AAV isolates achieved clinical benefit for a number of patients suffering from monogenetic disorders. However, high vector doses were required and the presence of pre-existing neutralizing antibodies precluded a number of patients from participation. Further challenges are related to AAV's tropism that lacks cell type selectivity resulting in off-target transduction. Conversely, specific cell types representing important targets for gene therapy like stem cells or endothelial cells show low permissiveness. To overcome these limitations, elegant rational design- as well as directed evolution-based strategies were developed to optimize various steps of AAV's host interaction. These efforts resulted in next generation vectors with enhanced capabilities, that is increased efficiency of cell transduction, targeted transduction of previously non-permissive cell types, escape from antibody neutralization and off-target free in vivo delivery of vector genomes. These important achievements are expected to improve current and pave the way towards novel AAV-based applications in gene therapy and regenerative medicine.
authors: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany; Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Sites Bonn-Cologne and Hannover-Braunschweig, Germany; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany. Electronic address: buening.hildegard@mh-hannover.de.
authors: Hildegard
authors: H
authors: Büning
authors: Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Sites Bonn-Cologne and Hannover-Braunschweig, Germany; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors: Anke
authors: A
authors: Huber
authors: Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Sites Bonn-Cologne and Hannover-Braunschweig, Germany; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors: Liang
authors: L
authors: Zhang
authors: Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), Partner Sites Bonn-Cologne and Hannover-Braunschweig, Germany; Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany.
authors: Nadja
authors: N
authors: Meumann
authors: University Cancer Center Leipzig (UCCL), Leipzig, Germany.
authors: Ulrich
authors: U
authors: Hacker
mesh_terms: D000818:Animals; D002213:Capsid; D002467:Cell Nucleus / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D054884:Host-Pathogen Interactions; D006801:Humans