Layer-specific nanophotonic delivery of therapeutic opsin-encoding genes into retina.
Layer-specific nanophotonic delivery of therapeutic opsin-encoding genes into retina.
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DOI：
10.1016/j.exer.2021.108444
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发表时间：
2021-04
影响因子：
3.4
通讯作者：
Mohanty, Samarendra
中科院分区：
文献类型：
--
作者：
Batabyal, Subrata;Kim, Sanghoon;Wright, Weldon;Mohanty, Samarendra
近年来，基因治疗已被证明是一种很有前途的治疗方法，用于治疗视觉障碍，通过替换无功能的基因或通过在视网膜细胞中引入光敏蛋白（视蛋白）作为人工光感受器。传统的基于病毒载体的基因递送方法通常面临着由于免疫遗传反应、非预期的非靶向递送、由于免疫排斥导致的重复重新给药的不可行性以及复杂的制造工艺而导致的限制，从而导致翻译成功的显著障碍。在这方面，非病毒递送提供了更安全、更简单和具有成本效益的替代方案。然而，大多数非病毒方法缺乏空间和/或细胞特异性，并受到低转染效率和细胞毒性的限制。在这里，我们提出了一种微创，非病毒和临床上可翻译的安全靶向基因递送方法，利用功能化的等离子体金纳米棒（fGNRs，靶向附着到感兴趣的器官的特定细胞类型）和空间靶向受控光照射。通过使用细胞特异性fGNR同时进行光照射，实现了视蛋白编码基因在双极和神经节细胞层中的靶向体内递送和表达。通过电生理学、光学相干断层扫描、眼内压和其他分析方法（共聚焦显微镜、免疫组织化学）检查了与使用fGNR和光照射转导视蛋白编码基因相关的安全性和毒性评价。基于光的非病毒视蛋白基因递送提供了基于病毒载体的基因递送的安全且有效的替代方案，并有望用于视网膜变性疾病的矫正性细胞特异性基因疗法。
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.
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影响因子：
4.2
作者：
Alexander, IE;Russell, DW;Miller, AD
通讯作者：
Miller, AD
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
DOI：
10.1523/jneurosci.2246-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Adamantidis AR;Tsai HC;Boutrel B;Zhang F;Stuber GD;Budygin EA;Touriño C;Bonci A;Deisseroth K;de Lecea L
通讯作者：
de Lecea L
影响因子：
64.5
作者：
BURRIDGE, K;FERAMISCO, JR
通讯作者：
FERAMISCO, JR
DOI：
10.1007/978-1-4939-7522-8_12
发表时间：
2018-01-01
期刊：
RETINAL GENE THERAPY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gaub, Benjamin M.;Berry, Michael H.;Flannery, John G.
通讯作者：
Flannery, John G.