Glaucoma Epigenetic Treatment with Light Activated CRISPR-dCas9

使用光激活 CRISPR-dCas9 进行青光眼表观遗传学治疗

• 批准号: 1948722
• 负责人: Le Qiu
• 金额: $ 60万
• 依托单位: Beth Israel Deaconess Medical Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1948722&HistoricalAwards=false
• 关键词: Glaucoma; Epigenetic; Treatment; Light; Activated

Glaucoma is the leading cause of irreversible blindness worldwide. Loss of vision in glaucoma is caused by the death of retinal neurons that convey visual information from the retina to the brain. Currently, there is no cure for glaucoma. In recent years it has become apparent that most forms of glaucoma are inherited and the genetic factors play a key role in its onset and development. Glaucoma-causative genes appear to be very promising therapeutic targets for glaucoma treatment. Recently, it has also been discovered that the loss of the retinal neuron function could not only be slowed down but could also be reversed. Thus, it seems hopeful that not only could the glaucoma’s progress be slowed down using genetic and epigenetic approaches, but it may also be possible to reverse its progression with retinal neuron and optic nerve axon regeneration.The investigators propose to develop a novel visible light activated CRISPR-dCas9 based epigenetic method for glaucoma treatment and the potential for vision restoration. CRISPR is a revolutionary new technology for versatile genome alterations but the high frequency of off-target activity induced by CRISPR at sites other than the intended on-target one is a major concern, especially for therapeutic and clinical applications. This problem could be solved with a light activatable version of CRISPR, which enables localized genetic alterations, limiting off-target activity only to the illuminated cells. They will develop and construct a new instrument for localized CRISPR activation with visible light. The proposed novel light activated CRISPR-dCas9 based epigenetic method for glaucoma treatment and vision restoration is transformative since the platform could have a profound impact on developing highly effective ophthalmic therapies for a wide range of retinal disorders.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

青光眼是全世界不可逆转失明的主要原因。青光眼患者的视力丧失是由将视觉信息从视网膜传递到大脑的视网膜神经元死亡引起的。目前，青光眼无法治愈。近年来，人们发现大多数形式的青光眼都是遗传性的，遗传因素在其发病和发展中起着关键作用。青光眼致病基因似乎是青光眼治疗非常有希望的治疗靶点。最近还发现，视网膜神经元功能的丧失不仅可以减缓，而且可以逆转。因此，不仅可以通过遗传和表观遗传方法减缓青光眼的进展，而且还可以通过视网膜神经元和视神经轴突再生来逆转青光眼的进展，这似乎是有希望的。研究人员建议开发一种新型可见光激活的基于 CRISPR-dCas9 的表观遗传方法，用于青光眼治疗和视力恢复的潜力。 CRISPR 是一种革命性的新技术，可用于多功能基因组改变，但 CRISPR 在预期的靶向位点以外的位点诱导的高频率脱靶活性是一个主要问题，特别是对于治疗和临床应用。这个问题可以通过光激活的 CRISPR 来解决，它可以实现局部基因改变，将脱靶活性限制在被照射的细胞上。他们将开发并构建一种利用可见光进行局部 CRISPR 激活的新仪器。拟议的基于光激活 CRISPR-dCas9 的新型表观遗传学方法用于青光眼治疗和视力恢复具有变革性，因为该平台可能对开发针对多种视网膜疾病的高效眼科疗法产生深远影响。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Rapid detection and identification of bacteria directly from whole blood with light scattering spectroscopy based biosensor

利用基于光散射光谱的生物传感器直接从全血中快速检测和鉴定细菌

• DOI: 10.1016/j.snb.2021.130489
• 发表时间: 2021
• 期刊: Sensors and Actuators B: Chemical
• 作者: Qiu, Le;Zhang, Lei;Horowitz, Gary L.;Turzhitsky, Vladimir;Coughlan, Mark F.;Glyavina, Maria;Khan, Umar;Zakharov, Yuri N.;Vitkin, Edward;Itzkan, Irving
• 通讯作者: Itzkan, Irving

C-CLASS microscopy allows the detection of nanoscale changes in chromatin structure

C-CLASS 显微镜可以检测染色质结构的纳米级变化

• DOI: 10.1117/12.2667044
• 发表时间: 2023
• 期刊: Proc. of SPIE
• 作者: Coughlan, Mark F.;Pettinato, Giuseppe;Glyavina, Maria M.;Zhang, Xuejun;Chen, Liming;Khan, Umar;Upputuri, Paul K.;Zakharov, Yuri N.;Zhang, Lei;Qiu, Le
• 通讯作者: Qiu, Le

Laser Scanning Microscope Based Digital Holography for biomedical application

基于激光扫描显微镜的数字全息术在生物医学应用中的应用

• DOI: 10.1364/dh.2023.htu5c.4
• 发表时间: 2023
• 期刊: pcAOP
• 作者: Zakharov, Iurii;Muravyeva, Maria;Perelman, Lev T.
• 通讯作者: Perelman, Lev T.

A portable light scattering system for detecting expelled droplets to assess Covid-19 transmission risk

便携式光散射系统，用于检测排出的液滴以评估 Covid-19 传播风险

• DOI: 10.1117/12.2608902
• 发表时间: 2022
• 期刊: Biomedical Applications of Light Scattering XII
• 作者: Coughlan, Mark F.;Sawhney, Mandeep S.;Pleskow, Douglas K.;Berzin, Tyler M.;Khan, Umar;Glyavina, Maria;Zhang, Xuejun;Chen, Liming;Upputuri, Paul K.;Sheil, Conor J.
• 通讯作者: Sheil, Conor J.

246.8: In Vivo Monitoring of Liver Organoids Differentiation Using Live-Screening-Optical Technologies

246.8：使用实时筛选光学技术体内监测肝脏类器官分化

• DOI: 10.1097/01.tp.0000886176.20263.10
• 发表时间: 2022
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Pettinato, Giuseppe;Coughlan, Mark F.;Zhang, Xuejun;Chen, Liming;Glyavina, Maria;Zakharov, Yuri N.;Zhang, Lei;Qiu, Le;Fisher, Robert A.;Perelman, Lev T.
• 通讯作者: Perelman, Lev T.