Near-Infrared Laser-Based Spatially Targeted Nano-enhanced Optical Delivery of Therapeutic Genes to Degenerated Retina

• Published in: Molecular therapy. Methods & clinical development Vol. 17; pp. 758 - 770
• Main Authors: Batabyal, Subrata, Gajjeraman, Sivakumar, Tchedre, Kissaou, Dibas, Adnan, Wright, Weldon, Mohanty, Samarendra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-06-2020; American Society of Gene & Cell Therapy; Elsevier
• Subjects: dry-AMD therapy; laser gene delivery; multi-characteristic opsin; nano-enhanced optical delivery; nano-manipulation; non-viral delivery; optogenetics; photoreceptor degeneration; retinal gene therapy; spatially-targeted gene delivery; spatially-targeted gene delivery; dry-AMD therapy; retinal gene therapy; optogenetics; non-viral delivery; laser gene delivery; multi-characteristic opsin; nano-manipulation; photoreceptor degeneration; nano-enhanced optical delivery
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2020.03.030

Non-viral delivery of therapeutic genes into targeted areas of retina is essential for re-functionalizing the retinal circuitry. While a focused ultrafast laser beam has been recently used for intra-ocular delivery of molecules, it poses the significant technical challenge of overcoming aberrations of the eye and maintaining a tightly focused spot on the retinal cell membrane. Furthermore, to minimize collateral damage and increase the throughput of gene delivery, we introduced a weakly focused near-infrared (NIR) continuous wave (CW) or pulsed laser beam on to the cells wherein the intensity is locally enhanced by gold nanorods bound to the cell membranes to permit gene insertion. Parametric optimization of nano-enhanced optical delivery (NOD) was carried out by varying the exposure time, as well as the power of the CW NIR beam or the energy of the pulsed NIR beam. Using this NOD method, therapeutic genes encoding for multi-characteristic opsins (MCOs) were delivered to spatially targeted regions of degenerated retina ex vivo as well as in vivo. NOD-mediated cell membrane-specific expression of MCOs in targeted retinal regions with photoreceptor degeneration will allow functional recovery in an ambient light environment.
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Nanoscope researchers describe a non-viral method using nanotechnology and light for in vivo delivery of the therapeutic multi-characteristic opsin gene into the targeted area of a photoreceptor-degenerated retina. This delivery approach mitigates limitation associated with viral methods such as immunogenic reaction and allows spatially targeted delivery for treatment of geographic atrophies, as in dry-AMD.