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

基本信息

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
项目类别：
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

项目摘要

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 - UValidate 平台的优化执行摘要：我们研究的总体目标是开发 UValidate™ 平台，能够测量化学物质的协同遗传毒性效应，特别是与紫外线照射相结合时，在第一阶段，平台已用于测量 FDA 批准的防晒霜组合的遗传毒性这项测试是为了回应越来越多的证据表明：防晒霜（含有多达六种活性成分的组合）正在渗入我们报告说，第一阶段的血流具有严重的脱靶效应。截至提交补充材料时，所有三个核心项目均已成功，并且已完成 90% 以上。 UValidate™ 系统在阿米莉亚现场正常运行并经过验证，可测试活性成分和在核心系统的开发过程中，相关化学品正在进行中。显然，LED UV-DNA 损伤诱导系统 (LUDIS) 具有额外的商业价值。 LUDIS 装置是一款全封闭、兼容培养箱、独立的基于 LED 的紫外线照射系统能够提供精确且极其可重复的 DNA 损伤水平（二聚体/光产物和/或氧化 DNA 损伤）对哺乳动物细胞的高通量开发。系统是项目早期遇到的技术问题的结果，特别是辐照使用基于细胞仪的 LED 每个 96 孔板需要数小时到数天的时间，这使得它与 LUDIS 旨在满足 UValidate™ 的高吞吐量要求。 96 孔板可在不到五分钟内测定紫外线（UVA1、UVA2 或 UVB）的遗传毒性水平 LUDIS 的潜在市场不仅限于皮肤护理，化妆品和光生物学实验室能够诱导精确、可重复的量。 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。目前，研究人员仅限于诱导多种形式。因此，LUDIS 单元解决了使用有毒化学品或辐射造成的 DNA 损伤的问题。 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量，此外，使用 LUDIS 代替。 DNA 损伤的化学诱导通过去除大部分 DNA 损伤来提高实验重现性实验误差的常见领域；稀释度和浓度的计算、化学代谢、化合物降解和溶解度问题。为了促进将 LUDIS 装置推向市场，我们创建了一个 I-CORPS 团队，其中包括 PI 和 CSO，Peter Sykora 博士 Sykora 博士是一位拥有 20 多年经验的 DNA 损伤和修复专家。经验和超过 25 篇与 DNA 损伤直接相关的同行评审出版物领域包括环境毒理学、线粒体 DNA 修复和年龄相关的神经退行性疾病。他还开发了包括CometChip™和Immuno-CometChip在内的技术他在华盛顿特区乔治敦大学讲授新兴分子技术。 Mark Chirikjian 先生是 LUDIS 平台并不断优化技术以实现更广泛应用的人。团队行业专家，Edvotek™ 现任首席执行官兼所有者，Edvotek™ 是一家教育科学公司，拥有令人印象深刻的长期财务记录，他是团队中不可或缺的一员。最后，Lucia Dussan 拥有原型制造和生产、物流和管理方面的专业知识。 Amelia Technologies 首席运营官，拥有质量控制和制造物流方面的专业知识。这些团队中的每一个都拥有著名的乔治城生物技术项目的硕士学位。成员明确表示能够投入完成 I-CORPS 计划所需的时间并热衷于参与该计划。应用程序 ID：934782 - UValidate 平台的优化