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Title: Nerve growth factor receptor-mediated gene transfer
Authors: Ma, N.
Wu, S.S.
Ma, Y.X.
Wang, X.
Zeng, J.
Tong, G.
Huang, Y.
Wang, S. 
Keywords: Dorsal root ganglia
Gene delivery
Nerve growth factor
PC12 cells
Issue Date: Feb-2004
Citation: Ma, N., Wu, S.S., Ma, Y.X., Wang, X., Zeng, J., Tong, G., Huang, Y., Wang, S. (2004-02). Nerve growth factor receptor-mediated gene transfer. Molecular Therapy 9 (2) : 270-281. ScholarBank@NUS Repository.
Abstract: One obstacle to effective gene therapies for neurological disorders lies in the cell-type diversity of the nervous system, making it difficult to direct gene delivery vectors to specific types of cells. To meet this challenge, we have developed a recombinant peptide-based gene delivery vector that targets nerve growth factor (NGF) receptors. The peptide comprises a cell-targeting domain derived from the NGF hairpin motif containing loops 1 and 2 linked to a DNA-binding domain composed of SPKR repeats. In PC12 cells, it activated the high-affinity NGF receptor, TrkA, and displayed NGF-like bioactivity by promoting neurite outgrowth and cell survival after serum deprivation. When combined with a low molecular weight of polyethylenimine (PEI), the peptide condensed plasmid DNA into nanoparticles that efficiently transferred exogenous genes into PC12 cells, enhancing reporter gene expression 5600-fold over peptide-free DNA/PEI complexes. Co-incubation with free NGF inhibited this effect. Furthermore, the peptide enhanced gene expression in NGF-receptor-rich rat primary cortex neurons but not glial cells. An in vivo experiment targeting TrkA-expressing dorsal root ganglia demonstrated that the peptide-containing complexes were 9- to 14-fold more efficient in transfection than controls. These properties make the chimeric peptide a promising gene delivery vector for targeting specific subtypes of neurons. Copyright © The American Society of Gene Therapy.
Source Title: Molecular Therapy
ISSN: 15250016
DOI: 10.1016/j.ymthe.2003.11.005
Appears in Collections:Staff Publications

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