title: Selective targeting of adenoviral vectors to neural precursor cells in the hippocampus of adult mice: new prospects for in situ gene therapy.
abstract: The adult brain contains neural precursor cells (NPC) that are attracted to brain lesions, such as areas of neurodegeneration, ischemia, and cancer. This suggests that NPC engineered to promote lineage-specific differentiation or to express therapeutic genes might become a valuable tool for restorative cell therapy and for targeting therapeutic genes to diseased brain regions. Here we report the identification of NPC-specific ligands from phage display peptide libraries and show their potential to selectively direct adenovirus-mediated gene transfer to NPC in adult mice. Identified peptides mediated specific virus binding and internalization to cultured neurospheres. Importantly, peptide-mediated adenoviral vector infection was restricted to precursor cells in the hippocampal dentate gyrus of pNestin-green fluorescent protein transgenic or C57BL/6 mice. Our approach represents a novel method for specific manipulation of NPC in the adult brain and may have major implications for the use of precursor cells as therapeutic delivery vehicles in the central nervous system.
authors.affiliation: Department of Vector Technology and Experimental Gene Therapy, Biomedical Research Center, Schillingallee 69, D-18057 Rostock, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.forename: Stefan J-P
authors.initials: SJ
authors.lastname: Haas
authors.forename: Steve
authors.initials: S
authors.lastname: Hildebrandt
authors.forename: Johanna
authors.initials: J
authors.lastname: Scheibe
authors.forename: Birthe
authors.initials: B
authors.lastname: Eckhoff
authors.forename: Tomás
authors.initials: T
authors.lastname: Racek
authors.forename: Gerd
authors.initials: G
authors.lastname: Kempermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Pützer
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*