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Newland, B,Abu-Rub, M,Naughton, M,Zheng, Y,Pinoncely, AV,Collin, E,Dowd, E,Wang, W,Pandit, A
Acs Chemical Neuroscience
GDNF Gene Delivery via a 2-(Dimethylamino)ethyl Methacrylate Based Cyclized Knot Polymer for Neuronal Cell Applications
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Deactivation enhanced atom transfer radical polymerization (DE-ATRP) glial cell line-derived neurotrophic factor (GDNF) DMAEMA transfection astrocytes dorsal root ganglia NEUROTROPHIC FACTOR PARKINSON INFUSION VECTORS THERAPY DEGRADATION LACTOFERRIN DOPAMINE DISEASE SYSTEM
Nonviral 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.
DOI 10.1021/cn4000023
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