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

基本信息

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
项目类别：
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

项目摘要

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）：用于临床用途的并行高通量药物遗传学分析测定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了解个体基因谱对这些过程的影响以及预测、预防和个性化医学的发展至关重要。 Maxwell Sensors Inc. 提议开发条形码蚀刻可检测微珠 (BEAM bead) 技术，该技术将数字条形码珠和分子化学结合起来，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分析。数字 BEAM 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，以在均质或异质介质中进行大型多重检测。使用 BEAM 微珠进行基因分型具有灵活性、高通量、易于制造、低成本大规模生产以及小批量一次反应等优点。在该项目的第一阶段，我们成功地（1）制造了10位BEAM磁珠，允许1,024（= 210）个独特的代码，使其成为世界上最高度复用的条形码磁珠； (2)设计构建了微流控换能器和荧光检测器，对荧光进行一一解码和检测； (3) 开发了P450 (CYP2A7)、KCNA5和ITPase的多重PCR，以及珠杂交； (4) 使用多重 PCR 扩增序列评估 SNP 基因分型测定。 II 期工作将重点关注用于临床应用的 BEAM 微珠平台的优化、BEAM 系统的设计和集成、用于对与药物反应相关的 SNP 进行基因分型的标准和定制 SNP 面板的设计，以及用于目标基因扩增和 SBE 杂交的多重 PCR 的开发。