title: Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity.
abstract: Neural stem/progenitor cells (NSPCs) have the potential to self-renew and to generate all neural lineages as well as to repopulate damaged areas in the brain. Our previous targeting strategies have indicated precursor cell heterogeneity between different brain regions that warrants the development of NSPC-specific delivery vehicles. Here, we demonstrate a target-specific adenoviral vector system for the in vivo manipulation of progenitor cells in the subventricular zone of the adult mouse brain. For this purpose, we identified a series of peptide ligands via phage display. The peptide with the highest affinity, SNQLPQQ, was expressed in conjunction with a bispecific adaptor molecule. To verify the targeting potential of the specific peptide, green fluorescent protein-expressing Ad vectors were coupled with the adaptor molecule and injected into the subventricular region of adult mice by stereotaxic surgery. An efficient and selective transduction of NSPCs in the SVZ was achieved, whereas hippocampal NSPCs were negative. Our results offer an expeditious and simple tool to produce retargeted viral vectors for a specific and direct in vivo manipulation of these progenitor cells. This powerful technique provides an opportunity to develop innovative strategies and express therapeutic genes in specific types of neural progenitor cells to allow success in treatment of brain disorders.
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Reetz
authors.affiliation: Department of Anatomy, University of Rostock, Gertrudenstr. 9, 18057, Rostock, Germany.
authors.forename: Steve
authors.initials: S
authors.lastname: Hildebrandt
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.|INP Greifswald, F.-Hausdorff-Str. 2, 17489, Greifswald, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Meier
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany.
authors.forename: Ottmar
authors.initials: O
authors.lastname: Herchenröder
authors.affiliation: Department of Anatomy, University of Rostock, Gertrudenstr. 9, 18057, Rostock, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Gläser
authors.affiliation: Department of Anatomy, University of Rostock, Gertrudenstr. 9, 18057, Rostock, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Witt
authors.affiliation: Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany. brigitte.puetzer@med.uni-rostock.de.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Pützer
authors.affiliation: Department of Anatomy, University of Rostock, Gertrudenstr. 9, 18057, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D020547:Lateral Ventricles / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D011485:Protein Binding
keywords: Adenoviral gene delivery; Brain stem cell targeting; Heterogeneity; Neural stem cells; Peptide; Subventricular zone