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Targeted nonviral delivery vehicles to neural progenitor cells in the mouse subventricular zone

Paper ID Volume ID Publish Year Pages File Format Full-Text
8696 602 2010 8 PDF Available
Title
Targeted nonviral delivery vehicles to neural progenitor cells in the mouse subventricular zone
Abstract

Targeted gene therapy can potentially minimize undesirable off-target toxicity due to specific delivery. Neuron-specific gene delivery in the central nervous system is challenging because neurons are non-dividing and also outnumbered by glial cells. One approach is to transfect dividing neural stem and progenitor cells (NSCs and NPCs, respectively). In this work, we demonstrate cell-specific gene delivery to NPCs in the brains of adult mice using a peptide-modified polymeric vector. Tet1, a 12-amino acid peptide which has been shown to bind specifically to neuronal cells, was utilized as a neuronal targeting ligand. The cationic polymer polyethylenimine (PEI) was covalently modified with polyethylene glycol (PEG) for in vivo salt stability and Tet1 for neuron targeting to yield a Tet1–PEG–PEI conjugate. When plasmid DNA encoding the reporter gene luciferase was complexed with Tet1–PEG–PEI and delivered in vivo via an injection into the lateral ventricle, Tet1–PEG–PEI complexes mediated increased luciferase expression levels in brain tissue when compared to unmodified PEI–PEG complexes. In addition, cells transfected by Tet1–PEG–PEI complexes were found to be exclusively adult NPCs whereas untargeted PEG–PEI complexes were found to transfect a heterogenous population of cells. Thus, we have demonstrated targeted, nonviral delivery of nucleic acids to adult NPCs using the Tet1 targeting ligand. These materials could potentially be used to deliver therapeutic genes for the treatment of neurodegenerative diseases.

Keywords
Gene therapy; Nanoparticle; Peptide
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Targeted nonviral delivery vehicles to neural progenitor cells in the mouse subventricular zone
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 8, March 2010, Pages 2417–2424
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us