The clinical potential of optogenetic interrogation of pathogenesis.
The clinical potential of optogenetic interrogation of pathogenesis.
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DOI：
10.1002/ctm2.1243
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发表时间：
2023-05
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
基于视蛋白的光遗传学已经成为一种利用光来控制蛋白质构象的强大生物医学工具。这种能力最初被证明可以控制穿过细胞膜的离子流动，从而能够精确控制神经元或肌肉细胞等可兴奋细胞的动作电位。光遗传学的进一步发展融合了更多种类的可光激活蛋白质，并导致了对生物过程的灵活控制，如基因表达和信号转导，以及光学显微镜中常用的光源，如LED或激光。得益于精确的基因靶向特异性和卓越的时空分辨率，光遗传学为研究健康和疾病的生理和病理机制提供了新的生物学见解。最近，由于方便的光线进入眼睛，它的临床潜力已经开始被利用，特别是在治疗失明方面。这项工作总结了目前临床试验的进展，并简要概述了常用的光激活蛋白的基本结构和光物理。我们重点介绍了最近的成就，如嵌合抗原受体的光遗传控制，CRISPR-Cas系统，基因表达，以及细胞器动力学。我们讨论了当前光遗传研究面临的概念创新和技术挑战。在这样做的过程中，我们提供了一个框架，展示了光遗传学在生物医学研究中日益增长的应用，并可能为基于这一使能技术的新型精确医学战略提供信息。基于视蛋白和无视蛋白的光遗传学利用光来调节膜电导和蛋白质与蛋白质的相互作用。临床试验的重点是治疗由于光线容易传递而导致的失明。蛋白质工程改善了可光激活蛋白质的光物理和生物相容性。无视蛋白的光遗传学扩展了临床应用，如嵌合抗原受体(CAR)和基于规则间隔短回文重复序列(CRISPR)的基因组工程和转录调控。
Opsin‐based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye. This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR‐Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research. In doing so, we provide a framework that showcases ever‐growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology. Opsin‐based and opsin‐free optogenetics employs light to modulate membrane conductance and protein‐protein interaction. Clinical trials focus on treating blindness due to the easy delivery of light. Protein engineering improves the photophysics and biocompatibility of photoactivatable proteins. Opsin‐free optogenetics expands clinical applications such as the chimeric antigen receptor (CAR) and clustered regularly interspaced short palindromic repeats (CRISPR)‐based genomic engineering and transcriptional regulation.
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影响因子：
3.6
作者：
Baskar R;Lee KA;Yeo R;Yeoh KW
通讯作者：
Yeoh KW
影响因子：
4.6
作者：
Senova S;Poupon C;Dauguet J;Stewart HJ;Dugué GP;Jan C;Hosomi K;Ralph GS;Barnes L;Drouot X;Pouzat C;Mangin JF;Pain F;Doignon I;Aron-Badin R;Brouillet E;Boyden ES;Mitrophanous KA;Hantraye P;Palfi S
通讯作者：
Palfi S
DOI：
10.1016/j.pbiomolbio.2014.07.001
发表时间：
2014-08
影响因子：
3.8
作者：
Ambrosi CM;Klimas A;Yu J;Entcheva E
通讯作者：
Entcheva E
影响因子：
25
作者：
Banghart, M;Borges, K;Kramer, RH
通讯作者：
Kramer, RH
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K