HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 2007-0238v1 25/11/2910    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schmidt, A. Articles by Pützer, B. M. Search for Related Content PubMed PubMed Citation Articles by Schmidt, A. Articles by Pützer, B. M.

TECHNOLOGY DEVELOPMENT

Selective Targeting of Adenoviral Vectors to Neural Precursor Cells in the Hippocampus of Adult Mice: New Prospects for In Situ Gene Therapy

Anke Schmidt^a, Stefan J.-P. Haas^b, Steve Hildebrandt^a, Johanna Scheibe^a, Birthe Eckhoff^b, Tomá Racek^a, Gerd Kempermann^c, Andreas Wree^b, Brigitte M. Pützer^a

^aDepartment of Vectorology and Experimental Gene Therapy, Biomedical Research Center, and
^bInstitute of Anatomy, University of Rostock, Rostock, Germany;
^cCenter for Regenerative Therapies, Dresden, Germany

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

Correspondence: Brigitte M. Pützer, Ph.D., M.D., Department of Vector Technology and Experimental Gene Therapy, Biomedical Research Center, Schillingallee 69, D-18057 Rostock, Germany. Telephone: 49-381-4945066; Fax: 49-381-4945062; e-mail: brigitte.puetzer{at}med.uni-rostock.de

Received on March 30, 2007; accepted for publication on July 9, 2007.

First published online in STEM CELLS EXPRESS  July 19, 2007.


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.

Disclosure of potential conflicts of interest is found at the end of this article.