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

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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