Selective targeting of adenoviral vectors to neural precursor cells in the hippocampus of adult mice: New prospects for in situ gene therapy

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Anke Schmidt - , Universität Rostock (Autor:in)
  • Stefan J.P. Haas - , Universität Rostock (Autor:in)
  • Steve Hildebrandt - , Universität Rostock (Autor:in)
  • Johanna Scheibe - , Universität Rostock (Autor:in)
  • Birthe Eckhoff - , Universität Rostock (Autor:in)
  • Tomáş Racek - , Universität Rostock (Autor:in)
  • Gerd Kempermann - , Center for Regenerative Therapies Dresden (CRTD), Professur für Regenerationsgenomik (Autor:in)
  • Andreas Wree - , Universität Rostock (Autor:in)
  • Brigitte M. Pützer - , Universität Rostock, Biomedizinisches Forschungszentrum Rostock (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)2910-2918
Seitenumfang9
FachzeitschriftStem cells
Jahrgang25
Ausgabenummer11
PublikationsstatusVeröffentlicht - Nov. 2007
Peer-Review-StatusJa

Externe IDs

PubMed 17641242
ORCID /0000-0002-5304-4061/work/161408176

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Adenoviral vectors, Dentate gyrus, Gene therapy, Neural precursor/stem cells, Phage display, pNestin-green fluorescent protein transgenic mice