Optimization of the UValidate platform to measure genotoxicity associated with current problematic UV chemical blockers

优化 UValidate 平台以测量与当前有问题的紫外线化学阻断剂相关的遗传毒性

• 批准号: 10338776
• 负责人: DEAN ROSENTHAL
• 金额: $ 5.12万
• 依托单位: AMELIA TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10338776
• 关键词: Address; Aging; Amelia; Area; Biotechnology; Blood Circulation; Chemicals; Cosmetics; DNA Damage; DNA Repair; Development; Ecology; Exposure to; FDA approved; Goals; Hour; Incubators; Industry; Innovation Corps; Laboratories; Leeches; Logistics; Mammalian Cell; Measures; Metabolism; Mitochondrial DNA; Molecular; National Institute of Environmental Health Sciences; Oncology; Peer Review; Phase; Photobiology; Poison; Production; Publications; Quality Control; Radiation; Reporting; Reproducibility; Research; Research Personnel; Science; Site; Skin Care; Solubility; Sunscreening Agents; System; Technology; Testing; Time; Toxicology; Toxin; UV induced DNA damage; Ultraviolet B Radiation; United States National Institutes of Health; Universities; age related neurodegeneration; base; design; dimer; environmental toxicology; experience; exposed human population; genotoxicity; improved; irradiation; lectures; member; oxidative DNA damage; programs; prototype; response; skills; ultraviolet irradiation; wasting

Application ID: 934782 - Optimization of the UValidate platform Executive Summary: The overarching goal of our research was to develop the UValidate™ platform, able to measure the synergistic genotoxic-effect of chemicals particularly when combined with UV-irradiation. In Phase I, the platform has been used to measure the genotoxicity of combinations of FDA-approved sunscreen active ingredients. This testing was in response to a growing body of evidence suggesting that sunscreens (containing a combination of as many as six active ingredients) are leeching into the bloodstream having serious off-target effects. We report that the Phase I has been extremely successful and is greater than 90% complete. As of time of supplement submission, all three core- systems of UValidate™ are functional and validated at the Amelia site, testing of active ingredients and related chemicals is underway. During development of the core-systems, it became immediately apparent that the LED UV-DNA damage induction system (LUDIS) had additional commercial merit. The LUDIS unit is a fully enclosed, incubator compatible, stand-alone LED based UV-irradiation system that is able to deliver precise and extremely reproducible levels of DNA damage (dimer/ photoproduct and/or oxidative DNA damage) to mammalian cells in high throughput. Development of the LUDIS system is a result of technical problems encountered early in the project, specifically that irradiation using cytometer-based LEDs required hours to days per each 96-well plate making it incompatible with the high through-put requirement of UValidate™. Consequently, LUDIS was designed to deliver genotoxic levels of UV (UVA1, UVA2 or UVB) in less than five minutes with the 96-well format allowing for multiple simultaneous treatment regimes. The potential market for LUDIS goes beyond skin care, cosmetics and photobiology laboratories. With the ability to induce precise, reproducible amounts of DNA damage an important aspect in diverse fields including oncology, biomedicine, toxicology, environmental science and aging research. Currently, researchers are limited to inducing many forms of DNA damage using toxic chemicals or radiation. Hence, the LUDIS unit addresses core-initiatives of the NIH and NIEHS regarding increased experimental reproducibility and limiting human exposure to toxins, while concomitantly reducing the amount of toxic waste created. Further, using LUDIS instead of chemical induction of DNA damage improves experimental reproducibility by removing the most common areas of experimental error; calculation of dilutions and concentrations, chemical metabolism, compound degradation and solubility issues. To facilitate bringing the LUDIS unit to market we have created an I-CORPS teams that consists of the PI and CSO, Dr. Peter Sykora. Dr. Sykora is an expert in DNA damage and repair with over 20 years’ experience and more than 25 peer-reviewed publications relating directly to DNA damage in multiple fields including environmental toxicology, mitochondrial DNA repair and age-related neurodegeneration. He also has developed technologies including the CometChip™ and the Immuno-CometChip and lectures on emerging molecular technologies at Georgetown University, DC. He has developed the LUDIS platform and continues to optimize the technology for broader use. Mr. Mark Chirikjian is the team industry expert and current CEO and owner of Edvotek™, an educational science company that has an impressive decades long financial track record. He is an integral member of the team bring skills in prototype manufacture and production, logistics and management expertise. Finally, Lucia Dussan is the Amelia technologies COO, with expertise in quality control and manufacturing logistics. She comes to the team with a Masters in the prestigious Georgetown Biotechnology program. Each of these team members explicitly state that are able to devote the time needed to complete the I-CORPS program and are enthusiastic in their participation in the program. Application ID: 934782 - Optimization of the UValidate platform

应用程序ID：934782-UValify平台的优化 执行摘要： 我们研究的总体目标是开发UValify™平台，能够测量 协同遗传毒性--化学品的影响，特别是与紫外线辐射结合时。在第一阶段， 平台已经被用来测量FDA批准的防晒霜组合的遗传毒性 活性成分。这项测试是对越来越多的证据表明 防晒霜(含有多达六种有效成分的组合)正在渗入 血液有严重的偏离目标的影响。我们报告说，第一阶段已经非常 成功，并且已完成90%以上。截至提交补充材料的时间，所有三个核心- UVALIDATE™的系统在阿米莉亚现场运行和验证，测试有效成分和 相关化学品正在进行中。在核心系统的开发过程中，它立即成为 显然，LED UV-DNA损伤诱导系统(LUDIS)具有额外的商业价值。 LUDIS是一个完全封闭的、与孵化器兼容的、基于LED的独立紫外线照射系统 能够提供精确且极具重复性的DNA损伤水平(二聚体/感光产品 和/或氧化DNA损伤)。LUDIS的发展现状 系统是项目早期遇到的技术问题的结果，特别是辐射 使用基于细胞仪的LED，每个96孔板需要数小时到数天的时间，这使得它与 U VALIDATE™的高吞吐量要求。因此，LUDIS旨在提供 在不到五分钟的时间内达到紫外线(UVA1、UVA2或UVB)的遗传毒性水平，96孔格式允许 用于多种同时治疗方案。LUDIS的潜在市场不仅仅是护肤品， 化妆品和光生物学实验室。有能力诱导精确的、可重复性的 DNA损伤是肿瘤学、生物医学、毒理学等多个领域的一个重要方面， 环境科学和老龄化研究。目前，研究人员仅限于归纳出多种形式 使用有毒化学物质或辐射造成的DNA损伤。因此，LUDIS股处理以下核心举措： NIH和NIEHS关于提高实验重复性和限制人类接触 毒素，同时减少产生的有毒废物的数量。此外，使用LUDIS代替 化学诱导DNA损伤通过去除最大的 常见的实验误差领域：稀释度和浓度的计算、化学代谢、 化合物的降解和溶解问题。 为了促进将LUDIS单位推向市场，我们创建了一个i-Corps团队，由 派和CSO，Peter Sykora博士。Sykora博士是DNA损伤和修复方面的专家，有20多年的经验 与DNA损伤直接相关的经验和超过25篇同行评议的出版物 包括环境毒理学、线粒体DNA修复和与年龄相关的神经退行性变等领域。 他还开发了包括芯片™和免疫芯片在内的技术，并 乔治敦大学的新兴分子技术讲座。他开发出了 LUDIS平台，并继续优化该技术，以便更广泛地使用。马克·奇里克健先生是 团队行业专家、现任首席执行官兼教育科学公司Edvotek™的所有者 拥有令人印象深刻的长达数十年的财务记录。他是团队中不可或缺的一员带来技能 在样机制造和生产、物流和管理方面有专长。最后，露西娅·杜桑 Amelia Technologies首席运营官，在质量控制和制造物流方面拥有专业知识。她来了 在著名的乔治城生物技术项目中获得硕士学位的团队。这些队伍中的每一个 成员明确表示，能够投入完成i-Corps计划所需的时间 并对他们参与该计划充满热情。 应用程序ID：934782-UValify平台的优化