Abstract
In recent time, gene therapy has proven to be a promising remedial approach for treating visual disorders either by replacement of nonfunctioning gene(s) or by introduction of light sensitive proteins (opsins) as artificial photoreceptors in retinal cells. Conventional viral vector-based gene delivery method is often confronted with limitations due to immunogenetic reaction, unintended non-targeted delivery, non-feasibility of repeated re-dosing due to immunorejection, and complicated manufacturing process, leading to significant roadblock in translational success. In this regard, non-viral delivery provides a safer, simpler and cost-effective alternative. However, most of the non-viral approaches lack spatial and/or cellular specificity and limited by low transfection efficacy and cytotoxicity. Here, we present a minimally invasive, non-viral and clinically translatable safe targeted gene delivery method utilizing functionalized plasmonic gold nanorods (fGNRs, targeted to attach to specific cell types of the organ of interest) and spatially targeted controlled light irradiation. Targeted in-vivo delivery and expression of opsin-encoding gene in bipolar and ganglion cell layers were achieved by use of cell specific fGNRs concurrent with light irradiation. Evaluation of safety and toxicity associated with the transduction of opsin-encoding genes by use of fGNRs and light irradiation were examined by electrophysiology, Optical coherence tomography, intra-ocular pressure and other analytical methods (confocal microscopy, immunohistochemistry). The non-viral light-based opsin-gene delivery provides a safe and effective alternative to viral-vector based gene delivery and holds promise for corrective cell-specific gene therapies for retinal degenerative diseases.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.