Mutational profiling in human cells as an in vitro alternative to in vivo mutagenicity assessments

人体细胞突变分析作为体内致突变性评估的体外替代方案

• 批准号: 10696867
• 负责人: LESLIE RECIO
• 金额: $ 91.03万
• 依托单位: SCITOVATION, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-23 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10696867
• 关键词: Amendment; Animal Testing; Animals; Biological Assay; Cell Cycle; Cell Line; Cells; Chemicals; Chromosome abnormality; Client; Congenital Abnormality; Cosmetics; DNA; DNA Damage; Data; Detection; Development; Enzymes; European Union; Event; Food Additives; Gene Mutation; Genetic; Genome; Goals; Hazard Identification; Hepatocyte; Heritability; Human; Human Cell Line; Human Genome; In Vitro; Induced Mutation; Liver; Mammalian Cell; Measures; Metabolic; Methodology; Methods; Modeling; Mutagenicity Tests; Mutagens; Mutation; Mutation Fixation; Nature; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Poison; Public Health; Risk Assessment; Rodent; Sales; Scheme; Small Business Innovation Research Grant; System; Techniques; Test Result; Testing; Time; Toxic effect; Toxicity Tests; Toxicogenetics; Toxicology; Transgenic Organisms; Validation; Vision; analytical method; carcinogenesis; cost; daughter cell; dosimetry; drug candidate; environmental chemical; experimental study; follow-up; genotoxicity; improved; in vitro Assay; in vitro testing; in vivo; innovation; micronucleus; mutation assay; nervous system disorder; new technology; next generation; next generation sequencing; novel strategies; novel therapeutics; response; safety assessment; screening; success; transmission process; validation studies

PROJECT SUMMARY Mutations are heritable changes in the cellular genome and are key events in the induction of cancer, birth defects, and neurological diseases. The lack of a mutagenicity bioassay in human cells is a major data gap in the genetic toxicology test battery used by regulatory agencies for hazard identification and quantitative risk assessments. ScitoVation is developing a New Approach Methodologies (NAMs) combining human cells and Error Corrected Next Generation Sequencing as an in vitro alternative to current regulatory mammalian cell mutagenicity assessment using rodent cell lines, and as an in vitro alternative to in vivo mutation assays.

项目概要 突变是细胞基因组中的可遗传变化，是诱导癌症、出生的关键事件 缺陷和神经系统疾病。人类细胞中缺乏致突变性生物测定是一个主要的数据缺口 监管机构用于危险识别和定量风险的遗传毒理学测试电池 评估。 ScitoVation 正在开发一种新方法 (NAM)，将人体细胞与 纠错下一代测序作为当前调节哺乳动物细胞的体外替代品 使用啮齿动物细胞系进行致突变性评估，并作为体内突变测定的体外替代方法。