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Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity

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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.

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Acknowledgments

The authors thank Anja Stoll for her excellent technical assistance and Bhavani Kowtharapu for cloning lentiviral vectors. This work was supported by the German Research Foundation (DFG) grant PU 188/8-1, WR 20/2-1 and Research funding provided by the Medical Faculty of Rostock University (FORUN program).

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Anke Schmidt

    Present address: INP Greifswald, F.-Hausdorff-Str. 2, 17489, Greifswald, Germany

Authors and Affiliations

  1. Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Schillingallee 69, 18057, Rostock, Germany

    Julia Reetz, Anke Schmidt, Claudia Meier, Ottmar Herchenröder & Brigitte M. Pützer

  2. Department of Anatomy, University of Rostock, Gertrudenstr. 9, 18057, Rostock, Germany

    Steve Hildebrandt, Anne Gläser, Martin Witt & Andreas Wree

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  1. Julia Reetz
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Corresponding author

Correspondence to Brigitte M. Pützer.

Additional information

J. Reetz, S. Hildebrandt, B. M. Pützer, and A. Wree contributed equally to this work.

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Reetz, J., Hildebrandt, S., Schmidt, A. et al. Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity. Brain Struct Funct 221, 2049–2059 (2016). https://doi.org/10.1007/s00429-015-1025-8

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  • DOI: https://doi.org/10.1007/s00429-015-1025-8

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