SBIR Phase II: An Innovative Full-Thickness Human Skin Model for Increased Throughput Screening in Drug Discovery

SBIR II 期：创新的全层人体皮肤模型，可提高药物发现中的筛选通量

• 批准号: 1058591
• 负责人: Kenneth Gratz
• 金额: $ 49.99万
• 依托单位: Stratatech Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-15 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1058591&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Innovative; Full

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. 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.

这个小型企业创新研究（SBIR）第二阶段项目提出开发一种高通量检测方法，该方法结合了能够准确识别和表征DNA损伤的3-D皮肤模型。目前迫切需要改进的遗传毒性检测方法用于药物开发中的安全性筛选。筛选药物化合物的方法通常是昂贵的、耗时的，并且通常不能提供对体内行为的准确描述。该项目的第一阶段开发了一种可用于一系列毒理学测定的全层皮肤模型。II期将通过将荧光报告构建体并入96孔皮肤模型中来解决当前遗传毒性测定的局限性，以创建高通量并准确区分遗传毒素类别的测定。这项研究的更广泛的影响是开发一种比现有替代品信息更丰富，更准确，更高通量的遗传毒性筛选。 开发准确的体外检测方法不仅可以减少对动物试验的需求，还可以通过更好地预测人体反应来降低临床试验中患者的风险。毒性已成为药物开发过程中产品失败的主要原因之一。这种检测在开发过程中早期识别和消除有害化合物的能力可以显著降低成本并加快药物开发的时间轴。除了这些药物和化学筛选的直接贡献外，该测定提供的机制数据将为DNA损伤的基础科学研究提供有价值的工具。