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.

项目总结/摘要： EF Therapeutics，Inc.专注于将专有/专利工艺添加到标准方法中， 电介导的DNA递送。这项研究旨在帮助创建一个设备， 制造合作伙伴，这将是商业上可行的使用在美国，并最终其余的 世界EF Therapeutics的存在是因为基因治疗尚未成为现实，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一般困难是，在体内递送基因的方法不容易。 vivo还没有达到期望的可靠性和控制水平。体内电穿孔是一种方法 在临床前研究中已经取得了成功。进行了这些研究 将该技术用于各种应用。总的来说，它们证明了 这种方法使其适用于任何组织。这些研究为大约130个临床研究铺平了道路。 在体内使用该技术的试验。因此，有明确的研究和临床应用， DNA递送方法。但是，该方法可以改进，因为它仍然缺乏 控制/可靠性。其中一个原因是，用于感应的电脉冲的特性 基于动物模型中的优化，DNA摄取对于特定组织类型通常是固定的。 在临床环境中，这些可能对类似组织几乎没有可翻译性，因为模型可能不 与人体组织相同此外，个体与个体之间存在差异。因此，使用 相同的电脉冲（或电剂量）将DNA输送到特定类型的组织是不可能的。 每次在该组织类型中使用该方法时都是最佳的。不幸的是，这是目前的状态， 条实时定制/调整电治疗的手段可以避免这个问题， 增加了该方法的效率/可靠性。现有技术的另一个问题是， 电穿孔影响细胞膜，并且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，因为它们会影响膜流动性。这 提出的目标是将一家名为EF Therapeutics的小企业向前推进一步， 将上述两个方面结合起来最终改善DNA递送。的基础 这项研究是初步的数据，表明在定制的情况下， 单独使用脉冲或适度的温度升高。研究计划包括确定和 验证最终将用于商业/临床器械的两个关键组件。第一个是 加热和控制目标组织中的温度的系统。第二种是测量组织的方法 脉动期间真实的阻抗。这项研究的完成将消除一个障碍， 目前正在进行的商业化。