Improved functional recovery of injured spinal cords by efficient siRNA delivery using photomechanical waves

The formation of a glial scar after spinal cord injury (SCI) is one of the inhibitory factors for axonal regeneration. The cellular structure of a glial scar is mainly composed of reactive astrocytes that overexpress the intermediate filament (IF) proteins such as glial fibrillary acidic protein (GFAP) and vimentin. These proteins work as both physical and biochemical barriers for axonal growth in injured spinal cord. Thus, it would be an attractive strategy for the treatment of SCI to silence the over-expressed IF proteins. In the present study, we attempted to deliver small interfering RNAs (siRNAs) for GFAP and vimentin into injured spinal tissues in rats by applying photomechanical waves (PMWs) generated through expansion of intense laser-induced plasma. The treatment resulted in moderate silencing of the proteins at five days after SCI and decrease of the cavity area in the injured spinal tissue at three weeks after SCI. Moreover, we observed the significant functional recovery at five days after SCI when compared with those with SCI alone. These results demonstrate the efficacy of PMW-assisted gene therapy for SCI.