Batabyal Subrata, Gajjeraman Sivakumar, Tchedre Kissaou, Dibas Adnan, Wright Weldon, Mohanty Samarendra
Nanoscope Technologies, 1312 Brown Trail, Bedford, TX 76022, USA.
Mol Ther Methods Clin Dev. 2020 Apr 7;17:758-770. doi: 10.1016/j.omtm.2020.03.030. eCollection 2020 Jun 12.
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 as well as . NOD-mediated cell membrane-specific expression of MCOs in targeted retinal regions with photoreceptor degeneration will allow functional recovery in an ambient light environment.
将治疗性基因非病毒递送至视网膜的靶向区域对于恢复视网膜回路功能至关重要。虽然最近已使用聚焦超快激光束进行眼内分子递送，但它面临着克服眼睛像差并在视网膜细胞膜上保持紧密聚焦光斑这一重大技术挑战。此外，为了使附带损伤最小化并提高基因递送通量，我们将弱聚焦近红外（NIR）连续波（CW）或脉冲激光束照射到细胞上，其中强度通过与细胞膜结合的金纳米棒局部增强，以允许基因插入。通过改变曝光时间以及CW NIR光束的功率或脉冲NIR光束的能量，对纳米增强光学递送（NOD）进行了参数优化。使用这种NOD方法，编码多特征视蛋白（MCO）的治疗性基因被递送至退化视网膜的空间靶向区域以及……。在具有光感受器退化的靶向视网膜区域中，NOD介导的MCO细胞膜特异性表达将在环境光环境中实现功能恢复。
