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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Anke Schmidt - , University of Rostock (Author)
  • Stefan J.P. Haas - , University of Rostock (Author)
  • Steve Hildebrandt - , University of Rostock (Author)
  • Johanna Scheibe - , University of Rostock (Author)
  • Birthe Eckhoff - , University of Rostock (Author)
  • Tomáş Racek - , University of Rostock (Author)
  • Gerd Kempermann - , Center for Regenerative Therapies Dresden, Chair of Genomics of Regeneration (Author)
  • Andreas Wree - , University of Rostock (Author)
  • Brigitte M. Pützer - , University of Rostock, Biomedical Research Center Rostock (Author)

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

Original languageEnglish
Pages (from-to)2910-2918
Number of pages9
JournalStem cells
Volume25
Issue number11
Publication statusPublished - Nov 2007
Peer-reviewedYes

External IDs

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

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

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