Light-enabled gene control for cardiac applications

用于心脏应用的光基因控制

• 批准号: 1705645
• 负责人: Emilia Entcheva
• 金额: $ 36.09万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1705645&HistoricalAwards=false
• 关键词: Light; enabled; gene; control; cardiac

This project will demonstrate that light-enabled gene patterning can control the human cardiac pacemaker region. Light-enabled inhibition of key culprit regions implicated in atrial fibrillation will be investigated. Exciting preliminary results on automated high-throughput all optical cardiac electrophysiology platforms using optogenetics was demonstrated and will be employed. This project builds upon the PI's optogenetic work in optical control of cardiomyocyte function by incorporating gene editing tools (CRISPR) to allow optical manipulation of gene expression. The optical localization, using CRISPR action, will be used to modify local gene expression in cardiac tissue constructs. The proposal covers unexplored territory in cardiac pacing and has significant transformative potential.

该项目将证明，光激活基因模式可以控制人类心脏起搏器区域。心房颤动涉及的关键罪魁祸首区域的光激活抑制将被调查。在使用光遗传学的自动化高通量全光学心脏电生理平台上展示了令人兴奋的初步结果，并将被采用。该项目建立在PI在心肌细胞功能光学控制方面的光遗传学工作基础上，通过结合基因编辑工具（CRISPR）来允许基因表达的光学操作。利用CRISPR作用的光学定位将用于修饰心脏组织结构中的局部基因表达。该提案涵盖了心脏起搏的未开发领域，具有重大的变革潜力。

项目成果

Optical Interrogation of Sympathetic Neuronal Effects on Macroscopic Cardiomyocyte Network Dynamics

• DOI: 10.1016/j.isci.2020.101334
• 发表时间: 2020-07-24
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Burton, Rebecca-Ann B.;Tomek, Jakub;Bub, Gil
• 通讯作者: Bub, Gil

Protein and mRNA Quantification in Small Samples of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in 96-Well Microplates.

• DOI: 10.1007/978-1-0716-2261-2_2
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)

Adeno-Associated Virus Mediated Gene Delivery: Implications for Scalable in vitro and in vivo Cardiac Optogenetic Models

• DOI: 10.3389/fphys.2019.00168
• 发表时间: 2019-03-05
• 期刊: FRONTIERS IN PHYSIOLOGY
• 影响因子: 4
• 作者: Ambrosil, Christina M.;Sadanandal, Gouri;Entcheva, Emilia
• 通讯作者: Entcheva, Emilia