Remote-Control Mechano-Genetics and Epigenetics for Live Cell Manipulation

用于活细胞操作的远程控制机械遗传学和表观遗传学

• 批准号: 9765353
• 负责人: Yingxiao Wang
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765353
• 关键词: Biochemical; Biological; Biological Process; Biological Sciences; Biology; Biosensing Techniques; Biosensor; Calcium Signaling; Cell physiology; Cells; Communities; Coupled; Development; Dreams; Engineering; Epigenetic Process; Event; Feedback; Fluorescence Resonance Energy Transfer; Gene Activation; Gene Expression; Genes; Genetic; Genetic Engineering; Genetic Programming; Genetic Transduction; Genomics; Guide RNA; Imagery; Lead; Mechanics; Medical; Membrane; Methods; Microbubbles; Molecular; One-Step dentin bonding system; Optics; Organism; Output; Proteins; Reading; Regulation; Reporter Genes; Resolution; Science; Signal Transduction; Technology; Therapeutic; Time; Tissues; Transcription Coactivator; Ultrasonic Transducer; Ultrasonic wave; Ultrasonics; Ultrasonography; base; biomedical scientist; cellular engineering; clinical application; design; digital; engineered T cells; epigenetic regulation; experience; live cell imaging; mechanical force; meter; nuclease; optogenetics; pressure; prototype; remote control; sensor; spatiotemporal; tool; tumor

Remote-Control Mechano-Genetics and Epigenetics for Live Cell Manipulation It has been a long held dream for biomedical scientists to dynamically and precisely manipulate molecular activities and cellular functions in distance. Our project aims to bring this dream one step closer to reality, by engineering cellular mechano-sensors to convert the remote ultrasonic signal into intracellular molecular signals, and by engineering genetic transduction modules (GTMs) to relay the molecular signals into dynamically and precisely controlled genetic and epigenetic signals. This remote-controlled mechano- genetics/epigenetics (ReCoM) technology should allow the live cell engineering and manipulation with high spatiotemporal resolution. Our team has ample experience in ultrasound, biosensing, live cell imaging, and molecular and cellular engineering technologies. We have already engineered a prototype ultrasound- activatable cell. Here we propose to systematically develop and optimize the modularized ReCoM technology in three steps: (1) Optimize mechano-sensors that can receive ultrasonic signals via micro-bubbles and convert them into intracellular biochemical signals; (2) Engineer GTMs to relay these specific molecular signals to genetic outputs; (3) Encode the GTMs with locus-specific genetic and epigenetic modulators to allow the remote, dynamic, and precise control of cellular function and fate. This approach should allow the remote-controlled genetic and epigenetic activation in live cells with a high spatiotemporal precision in a non- invasive manner for therapeutic applications. The method should also provide a general approach to dynamically control molecular and cellular functions for biological studies and clinical applications.

用于活细胞操作的远程控制机械遗传学和表观遗传学 动态、精确地操纵分子是生物医学科学家长期以来的梦想 远距离活动和细胞功能。我们的项目旨在使这一梦想更接近现实，通过 工程细胞机械传感器将远程超声波信号转换为细胞内分子 信号，并通过工程遗传转导模块（GTM）将分子信号传递到 动态且精确控制的遗传和表观遗传信号。这种遥控机械 遗传学/表观遗传学（ReCoM）技术应该允许活细胞工程和操作具有高 时空分辨率。我们的团队在超声、生物传感、活细胞成像和 分子和细胞工程技术。我们已经设计了一个超声波原型- 可激活细胞。在此我们提出系统化开发和优化模块化ReCoM技术 分三个步骤：（1）优化机械传感器，可以通过微泡接收超声波信号 将它们转化为细胞内生化信号； (2) 设计 GTM 来传递这些特定的分子 遗传输出信号； (3) 用位点特异性遗传和表观遗传调节剂对 GTM 进行编码 允许远程、动态和精确地控制细胞功能和命运。这种方法应该允许 远程控制活细胞中的遗传和表观遗传激活，在非非环境条件下具有高时空精度 用于治疗应用的侵入方式。该方法还应该提供一个通用方法 动态控制分子和细胞功能，用于生物学研究和临床应用。