NSF Award
1058591
This Small Business Innovation Research (SBIR) Phase II project proposes to develop a high-throughput assay incorporating 3-D skin models capable of accurately identifying and characterizing DNA damage. There is an urgent need for improved genotoxicity assays for safety screening in drug development. The process by which drug compounds are usually screened is expensive, time-consuming, and often does not provide an accurate depiction of in vivo behavior. Phase I of this project developed a full-thickness skin model that can be used in a range of toxicological assays. Phase II will address the limitations of current genotoxicity assays by incorporating fluorescent reporter constructs into the 96-well skin model to create an assay that is high-throughput and accurately distinguishes between classes of genotoxins. <br/><br/>The broader impacts of this research are to develop a genotoxicity screen that is more informative, accurate, and high-throughput than existing alternatives. Development of accurate in vitro assays not only reduces the need for animal testing, but can also reduce the risk to patients included in clinical trials by providing better predictions of the human response. Toxicity has become one of the leading reasons for product failure during drug development. The ability for this assay to identify and eliminate harmful compounds earlier in the development process could significantly reduce the costs and accelerate the timeline of drug development. In addition to these direct contributions for drug and chemical screening, the mechanistic data provided by this assay will provide a valuable tool for basic science research into DNA damage.
