Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection
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Effective gene.pdf
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3.94 MB
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Author(s)
Chang, Ming-Fong
Hsieh, Jung-Hsien
Chiang, Hao
Kan, Hung-Wei
Huang, Cho-Min
Lin, Bo-Shiou
Miaw, Shi-Chuen
Pan, Chun-Liang
Chao, Chi-Chao
Hsieh, Sung-Tsang
Date Issued
October 2016
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Chang, Ming-Fong, Jung-Hsien Hsieh, Hao Chiang, Hung-Wei Kan, Cho-Min Huang, Luke Chellis, Bo-Shiou Lin, et al. “Effective Gene Expression in the Rat Dorsal Root Ganglia with a Non-Viral Vector Delivered via Spinal Nerve Injection.” Scientific Reports 6, no. 1 (October 2016).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Sloan School of Management
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/srep35612
