Identification of impedance measurement devices, heating hardware, and operating parameters to augment instrumentation for a commercial in vivo electroporation system

识别阻抗测量装置、加热硬件和操作参数，以增强商业体内电穿孔系统的仪器

• 批准号: 10484502
• 负责人: RICHARD HELLER
• 金额: $ 22.58万
• 依托单位: EF THERAPEUTICS LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-17 至 2024-05-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484502
• 关键词: Address; Affect; Algorithms; Animal Model; Animals; Area; Biological; Businesses; Cancer Vaccines; Capital; Cell membrane; Cells; Characteristics; Clinic; Clinical; Clinical Trials; Communicable Diseases; Complex; Custom; DNA; DNA delivery; Data; Development; Devices; Dose; Electricity; Electrodes; Electroporation; Engineering; Feedback; Gene Delivery; Genes; Goals; Heating; Immune response; Immunotherapy; Individual; Intellectual Property; Lead; Legal patent; Manufacturer Name; Measurement; Measures; Mediating; Membrane Fluidity; Methods; Modeling; Names; Nature; Patients; Persons; Phase; Physiologic pulse; Process; Property; Public Health; Publishing; Research; Research Personnel; Rest; Skin; Small Business Technology Transfer Research; System; Technology; Temperature; Therapeutic; Therapeutic Uses; Time; Tissues; Vaccination; Variant; Work; base; clinical application; commercialization; cost; design; electric field; electric impedance; experimental study; gene therapy; human tissue; improved; in vivo; individual variation; instrument; instrumentation; phase 1 study; preclinical study; prototype; response; success; therapeutic DNA; translational barrier; uptake; voltage

PROJECT SUMMARY / ABSTRACT: EF Therapeutics, Inc is focused on adding proprietary/patented processes to the standard methods for electrically mediated DNA delivery. This study is designed to help create a device with our manufacturing partner that will be commercially viable for use in the US and eventually the rest of the world. EF Therapeutics exists because gene therapy is not yet a reality, but it is moving in the correct direction. One obstacle and general difficulty with gene delivery is that methods for delivering genes in vivo have not yet achieved a desired level of reliability and control. In vivo electroporation is a method for delivering DNA that has been successful in preclinical studies. These studies have been performed using the technology for a variety of applications. Collectively, they prove that the physical basis of the method makes it adaptable to any tissue. These studies paved the way for approximately 130 clinical trials that use the technology in vivo. Thus, there are clear research and clinical applications for this DNA delivery method. But, the method could be improved because it still suffers from lack of control/reliability. One reason for this is that the characteristics of the electric pulses used to induce DNA uptake are normally fixed for a particular tissue type based upon optimization in animal models. These may have little translatability to analogous tissues in clinical settings as models may not be identical to human tissues. In addition, there is variation from individual to individual. Thus, using the same electric pulses (or dose of electricity) to deliver DNA to a particular type of tissue is not likely to be optimal each time the method is used in that tissue type. Unfortunately, this is the current state of the art. A means of customizing/adapting electrical treatment in real-time could circumvent this issue and add to the efficiency/reliability of the method. Another issue with the state of the art is that in vivo electroporation affects cell membranes and has traditionally been performed at ambient temperature. Moderately increased temperatures could affect the results as they influence membrane fluidity. This goal proposed is to move a small business named EF Therapeutics one step forward in addressing these two aforementioned aspects in combination to ultimately improve DNA delivery. The basis for this study is preliminary data that indicate approximately 10-fold increases in delivery when customized pulses or moderate temperature increases are used alone. The research plan includes identifying and verifying two key components that will ultimately be used in a commercial/clinical device. The first is a system to heat and control temperature in target tissue. The second is a means for measuring tissue impedance in real time during pulsation. Completion of this study will remove an obstacle to commercialization that is currently in progress.

项目摘要/摘要： EF Therapeutics, Inc 致力于将专有/专利流程添加到标准方法中 电介导的 DNA 传递。这项研究旨在帮助我们创建一种设备 制造合作伙伴将在美国以及最终在其他国家/地区具有商业可行性 世界。 EF Therapeutics 的存在是因为基因疗法尚未成为现实，但它正在朝着正确的方向发展 方向。基因递送的一个障碍和普遍困难是在其中递送基因的方法 vivo 尚未达到理想的可靠性和控制水平。体内电穿孔是一种方法 用于提供在临床前研究中取得成功的 DNA。这些研究已经进行 将该技术用于各种应用。他们共同证明了 方法使其适用于任何组织。这些研究为大约 130 项临床研究铺平了道路。 使用该技术的体内试验。因此，该技术有明确的研究和临床应用 DNA 递送方法。但是，该方法还可以改进，因为它仍然缺乏 控制/可靠性。原因之一是用于感应的电脉冲的特性 根据动物模型的优化，特定组织类型的 DNA 摄取通常是固定的。 这些可能对临床环境中的类似组织几乎没有可转化性，因为模型可能不是 与人体组织相同。此外，个体与个体之间存在差异。因此，使用 使用相同的电脉冲（或电剂量）将 DNA 传递到特定类型的组织不太可能 每次在该组织类型中使用该方法时都是最佳的。不幸的是，这就是目前的状态 艺术。实时定制/调整电处理的方法可以避免这个问题 增加该方法的效率/可靠性。现有技术的另一个问题是体内 电穿孔影响细胞膜，传统上在环境温度下进行。 适度升高的温度可能会影响结果，因为它们会影响膜的流动性。这 提出的目标是推动一家名为 EF Therapeutics 的小企业在解决问题方面向前迈出一步 将上述两个方面结合起来，最终改善 DNA 递送。的基础 这项研究是初步数据，表明定制后交付量增加了大约 10 倍 单独使用脉冲或适度的温度升高。研究计划包括确定和 验证最终将在商业/临床设备中使用的两个关键组件。第一个是 系统加热和控制目标组织的温度。第二种是测量组织的手段 脉动期间实时阻抗。完成这项研究将消除一个障碍 目前正在进行商业化。