A Parallel High-Throughput Pharmacogenetic Profiling Assay for Clinical Use

临床应用的并行高通量药物遗传学分析测定

• 批准号: 7617859
• 负责人: Gao Chen
• 金额: $ 37.97万
• 依托单位: MAXWELL SENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617859
• 关键词: Affect; Agonist; Alleles; Automation; Behavior; Binding; Biological; Biological Assay; Buffers; CYP2A7 gene; Categories; Cessation of life; Chemistry; Clinical; Code; Computer software; Computers; Custom; Cytochrome P450; DNA; DNA Sequence; Data; Databases; Detection; Development; Diagnostic; Digit structure; Dimensions; Discrimination; Disease susceptibility; Dose; Drug Delivery Systems; Drug Design; Ensure; Enzymes; Evaluation; Family; Figs - dietary; Fluorescence; Future; Gene Amplification; Gene Proteins; Gene Targeting; Genes; Genetic; Genetic Variation; Genomics; Genotype; Goals; Hand; Haplotypes; Healthcare Industry; Human Genome; Immobilization; Individual; Inherited; Knowledge; Label; Lighting; Liquid substance; Literature; Magnetism; Medical; Medicine; Metabolism; Microfluidics; Miniaturization; Modeling; Molecular; Molecular Profiling; North America; Nucleic Acids; Oligonucleotides; Operative Surgical Procedures; Optics; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Pharmacologic Substance; Pharmacology; Phase; Plasma; Polymorphism Analysis; Population; Primer Extension; Process; Production; Property; Proteins; Pump; Reaction; Reader; Reading; Reagent; Research; Risk; Sampling; Scanning; Semiconductors; Sensitivity and Specificity; Signal Transduction; Single Nucleotide Polymorphism; Solutions; Specificity; Speed; Surface; Susceptibility Gene; System; Technology; Testing; Therapeutic; Time; Transducers; Treatment Protocols; Tube; Variant; Vial device; Width; Work; base; carboxyl group; chemical property; clinical application; clinically relevant; cost; density; design; design and construction; detector; digital; disorder prevention; disorder risk; drug development; drug discovery; drug metabolism; environmental chemical; flexibility; genetic profiling; improved; inosine triphosphatase; interest; light intensity; magnetic beads; nano; new technology; novel; novel strategies; patient population; pharmacogenetic testing; prototype; receptor; research study; response; sensor; small molecule

DESCRIPTION (provided by applicant): A Parallel High Throughput Pharmacogenetic Profiling Assay for Clinical Use Pharmacogenomic studies have already identified a number of genes whose SNP genotypes or haplotypes correlate with different individual drug responses, other metabolic processes or disease susceptibility. Thus the ability to determine genotypes quickly and accurately for medically relevant regions is critical to understanding the effects of an individual's genetic profile on these processes, and to the development of predictive, preventative and personalized medicine. Maxwell Sensors Inc. proposes to develop Barcode Etched Assayable Micro Bead (BEAM bead) technology, which combines digital barcoded beads and molecular chemistry for a pharmacogenetic SNP genotyping assay, which can be used for the high throughput molecular profiling of individuals. The digital BEAM beads are paramagnetic and are fabricated by photolithography to have thousands of identification codes and can be functionalized with nucleic acids, proteins or other small molecules to carry out large multiplexed assays in homogeneous or heterogeneous media. Genotyping using BEAM beads offers the advantages of flexibility, high throughput, easy fabrication, low cost mass production, and all in one reaction in small volumes. During Phase I of the project, we have successfully (1) fabricated 10 digit BEAM beads, allowing 1,024 (=210) unique codes, making it the most highly multiplexed barcode magnetic bead in the world; (2) designed and constructed a microfluidic transducer and fluorescence detector to decode and detect fluorescence one by one; (3) developed multiplex PCR for P450 (CYP2A7), KCNA5 and ITPase, and bead hybridization; and (4) evaluated the SNP genotyping assay using multiplex PCR amplified sequences. Phase II work will focus on optimization of the BEAM bead platform for clinical applications, design and integration of BEAM system, design of standard and custom SNP panels for genotyping SNPs relevant to drug responses, and development of multiplex PCR for target gene amplification and SBE hybridization.

描述（由申请人提供）：用于临床应用的平行高通量药物遗传学分析试验药物基因组学研究已经鉴定了许多基因，其SNP基因型或单倍型与不同的个体药物反应、其他代谢过程或疾病易感性相关。因此，快速准确地确定医学相关区域的基因型的能力对于理解个体的遗传谱对这些过程的影响以及预测性、预防性和个性化医学的发展至关重要。麦克斯韦传感器公司提出开发条形码蚀刻可测定微珠（BEAM微珠）技术，该技术将数字条形码微珠和分子化学结合用于药物遗传学SNP基因分型测定，可用于个体的高通量分子谱分析。数字BEAM微珠是顺磁性的，通过光刻法制造，具有数千个识别码，可以用核酸、蛋白质或其他小分子进行功能化，以在均质或非均质介质中进行大型多重测定。使用BEAM珠粒的基因分型提供了灵活性、高通量、易于制造、低成本大规模生产和小体积的一次反应的优点。在项目的第一阶段，我们成功地（1）制作了10位BEAM磁珠，允许1，024（=210）个唯一代码，使其成为世界上最高度复用的条形码磁珠;（2）设计并构建了微流控传感器和荧光检测器，以逐个解码和检测荧光;（3）建立了P450（CYP 2A 7）、KCNA 5和ITR的多重PCR和微珠杂交技术;（4）对多重PCR扩增的SNP基因分型方法进行了评价。第二阶段的工作将集中在优化BEAM珠平台的临床应用，设计和整合BEAM系统，设计标准和定制SNP面板的基因分型SNP相关的药物反应，并开发多重PCR的目标基因扩增和SBE杂交。