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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Chang MF,Hsieh JH,Chiang H,Kan HW,Huang CM,Chellis L,Lin BS,Miaw SC,Pan CL,Chao CC,Hsieh ST

doi

10.1038/srep35612

subject

Has Abstract

pub_date

2016-10-17 00:00:00

pages

35612

issn

2045-2322

pii

srep35612

journal_volume

6

pub_type

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