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GDNF Gene Delivery via a 2‑(Dimethylamino)ethyl Methacrylate Based Cyclized Knot Polymer for Neuronal Cell Applications
journal contribution
posted on 2013-04-17, 00:00 authored by B. Newland, M. Abu-Rub, M. Naughton, Y. Zheng, A. V. Pinoncely, E. Collin, E. Dowd, W. Wang, A. PanditNonviral genetic therapeutic intervention strategies
for neurological disorders hold great promise, but a lack of vector
efficacy, coupled with vector toxicity, continue to hinder progress.
Here we report the application of a newly developed class of polymer,
distinctly different from conventional branched polymers, as a transfection
agent for the delivery of glial cell line derived neurotrophic factor
(GDNF) encoding gene. This new 2-(dimethylamino)ethyl methacrylate
(DMAEMA) based cyclized knot polymer was studied for neuronal cell
transfection applications, in comparison to branched polyethyleneimine
(PEI). While showing a similar transfection profile over multiple
cell types, the cyclized knot polymer showed far lower toxicity. In
addition, transfection of Neu7 astrocytes with the GDNF encoding gene
was able to cause neurite outgrowth when cocultured with dorsal root
ganglia (DRGs). The cyclized knot polymer assessed here (PD-E 8%PEG),
synthesized via a simple one-pot reaction, was shown to have great
potential for neuronal gene therapy applications.
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DRGNeuronal Cell ApplicationsNonviraltransfection agentDMAEMAcell transfection applicationsneurotrophic factorvector efficacyPEIcause neurite outgrowthtransfection profileNeu 7 astrocytesvector toxicitycyclized knot polymerGDNF encoding geneencoding genedorsal root gangliaPEGGDNF Gene Deliveryintervention strategiescell typesCyclized Knot Polymerglial cell linegene therapy applications
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