title: Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection.
abstract: Delivering gene constructs into the dorsal root ganglia (DRG) is a powerful but challenging therapeutic strategy for sensory disorders affecting the DRG and their peripheral processes. The current delivery methods of direct intra-DRG injection and intrathecal injection have several disadvantages, including potential injury to DRG neurons and low transfection efficiency, respectively. This study aimed to develop a spinal nerve injection strategy to deliver polyethylenimine mixed with plasmid (PEI/DNA polyplexes) containing green fluorescent protein (GFP). Using this spinal nerve injection approach, PEI/DNA polyplexes were delivered to DRG neurons without nerve injury. Within one week of the delivery, GFP expression was detected in 82.8% ± 1.70% of DRG neurons, comparable to the levels obtained by intra-DRG injection (81.3% ± 5.1%, p = 0.82) but much higher than those obtained by intrathecal injection. The degree of GFP expression by neurofilament(+) and peripherin(+) DRG neurons was similar. The safety of this approach was documented by the absence of injury marker expression, including activation transcription factor 3 and ionized calcium binding adaptor molecule 1 for neurons and glia, respectively, as well as the absence of behavioral changes. These results demonstrated the efficacy and safety of delivering PEI/DNA polyplexes to DRG neurons via spinal nerve injection.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Chang
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Departments of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jung-Hsien
authors.initials: JH
authors.lastname: Hsieh
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Hao
authors.initials: H
authors.lastname: Chiang
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Kan
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Cho-Min
authors.initials: CM
authors.lastname: Huang
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Chellis
authors.affiliation: Department of Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Bo-Shiou
authors.initials: BS
authors.lastname: Lin
authors.affiliation: Department of Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Shi-Chuen
authors.initials: SC
authors.lastname: Miaw
authors.affiliation: Department of Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, No. 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Pan
authors.affiliation: Departments of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Department of Graduate Institute of Brain and Mind Science, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.|Departments of Clinical Center for Neuroscience and Behavior, National Taiwan University Hospital, Taipei, Taiwan.|Department of Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D007278:Injections, Spinal / Q000379:methods*; D010957:Plasmids / Q000008:administration & dosage; D011094:Polyethyleneimine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves
chemical_list: D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine