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Molecular Therapy
Article . 2004 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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Molecular Therapy
Article
License: CC BY NC ND
Data sources: UnpayWall
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Molecular Therapy
Article . 2004
License: CC BY NC ND
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Nerve Growth Factor Receptor-Mediated Gene Transfer

Authors: Ma, N.; Wu, S.S.; Ma, Y.X.; Wang, X.; Zeng, J.; Tong, G.; Huang, Y.; +1 Authors

Nerve Growth Factor Receptor-Mediated Gene Transfer

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.

Country
Singapore
Keywords

Male, Recombinant Fusion Proteins, Amino Acid Motifs, Genetic Vectors, 610, Receptors, Nerve Growth Factor, Transfection, PC12 Cells, Nerve growth factor, Ganglia, Spinal, Drug Discovery, Nerve Growth Factor, Genetics, Animals, Gene delivery, Rats, Wistar, Receptor, trkA, Dorsal root ganglia, Molecular Biology, Pharmacology, Neurons, Gene Transfer Techniques, PC12 cells, Peptide Fragments, Rats, DNA-Binding Proteins, Organ Specificity, Molecular Medicine, Receptor, Plasmids, Protein Binding

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    14
    popularity
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
14
Average
Average
Top 10%
hybrid