title: GDNF gene delivery via a 2-(dimethylamino)ethyl methacrylate based cyclized knot polymer for neuronal cell applications.
abstract: 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.
authors: Network of Excellence for Functional Biomaterials (NFB), National University of Ireland, Galway, Ireland.
authors: B
authors: B
authors: Newland
authors: M
authors: M
authors: Abu-Rub
authors: M
authors: M
authors: Naughton
authors: Y
authors: Y
authors: Zheng
authors: A V
authors: AV
authors: Pinoncely
authors: E
authors: E
authors: Collin
authors: E
authors: E
authors: Dowd
authors: W
authors: W
authors: Wang
authors: A
authors: A
authors: Pandit
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D018014:Gene Transfer Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000235:genetics*; D006801:Humans; D008689:Methacrylates / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011108:Polymers / Q000008:administration & dosage*
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008689:Methacrylates; D011108:Polymers; C049840:2-(dimethylamino)ethyl methacrylate
references: Mov Disord. 2006 Feb;21(2):136-41
references: 16470786
references: Gene Ther. 1998 May;5(5):712-7
references: 9797878
references: Nat Rev Genet. 2003 May;4(5):346-58
references: 12728277
references: Methods Mol Med. 2001;65:253-84
references: 21318759
references: Nanoscale. 2010 Dec;2(12):2718-23
references: 20835447
references: Mol Ther. 2009 Apr;17(4):641-50
references: 19223866
references: Chem Commun (Camb). 2012 Jan 14;48(4):585-7
references: 22113516
references: Brain Res. 1995 Feb 20;672(1-2):104-11
references: 7749731
references: Eur J Neurosci. 1998 Jan;10(1):57-63
references: 9753113
references: J Am Chem Soc. 2011 Aug 24;133(33):13130-7
references: 21744868
references: Chem Commun (Camb). 2010 Jul 14;46(26):4698-700
references: 20514386
references: J Cell Sci. 1994 Jun;107 ( Pt 6):1687-95
references: 7962209
references: Hum Gene Ther. 1996 Oct 20;7(16):1947-54
references: 8930654
references: Eur J Pharm Biopharm. 2012 Nov;82(3):465-74
references: 22952108
references: J Neurosci. 1997 Sep 15;17(18):7111-8
references: 9278545
references: Nat Med. 2003 May;9(5):589-95
references: 12669033
references: Ann Neurol. 2006 Mar;59(3):459-66
references: 16429411
references: J Gene Med. 2008 Mar;10(3):306-15
references: 18085726
references: J Gene Med. 2009 Sep;11(9):754-63
references: 19554623
references: ACS Chem Neurosci. 2012 Oct 17;3(10):744-52
references: 23077718
references: J Neurosurg. 2005 Feb;102(2):216-22
references: 15739547
references: Curr Protoc Neurosci. 2006 Aug;Chapter 3:Unit 3.19
references: 18428634
references: Science. 1993 May 21;260(5111):1130-2
references: 8493557
references: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8935-9
references: 7568047
references: Biomaterials. 2008 Jan;29(2):238-46
references: 17935779
references: Eur J Neurosci. 2002 Feb;15(4):589-601
references: 11886440
references: J Am Chem Soc. 2012 Mar 14;134(10):4782-9
references: 22353186
references: J Am Chem Soc. 2012 Oct 10;134(40):16554-7
references: 23013485
references: Biomaterials. 2011 Aug;32(23):5402-10
references: 21536325
references: J Neurol Sci. 1973 Dec;20(4):415-55
references: 4272516
references: Biomaterials. 2013 Mar;34(8):2130-41
references: 23245921
references: Neurosurg Focus. 2006 May 15;20(5):E1
references: 16711657