Twist-Biosensor: Novel single molecule microarray technology for DNA genotyping

Twist-Biosensor：用于 DNA 基因分型的新型单分子微阵列技术

• 批准号: 8455286
• 负责人: Alfredo Andres Celedon
• 金额: $ 15.33万
• 依托单位: SCANOGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-16 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455286
• 关键词: Alleles; Automobile Driving; Biological Markers; Biosensor; Blood; Blood specimen; CYP2C19 gene; Copy Number Polymorphism; Cytochrome P-450 CYP2D6; DNA; DNA Microarray Chip; Detection; Development; Devices; Drug Prescriptions; Drug usage; Enzyme Gene; Enzymes; Equipment; Event; Genes; Genetic; Genetic Markers; Genetic Variation; Genetic screening method; Genomics; Genotype; Hour; Human; Human Genetics; Label; Legal patent; Link; Measures; Medical; Medicine; Microarray Analysis; Mutation; Noise; Oligonucleotides; Patients; Pharmaceutical Preparations; Phase; Polymorphism Analysis; Positioning Attribute; Process; Reproducibility; Research Personnel; Sampling; Sensitivity and Specificity; Single Nucleotide Polymorphism; Stress; Techniques; Technology; Testing; Time; Training; United States Food and Drug Administration; base; clinical practice; cost; drug metabolism; genome wide association study; genotyping technology; new technology; novel; pharmacogenetic testing; prototype; public health relevance; rapid detection; response; single molecule; synthetic construct

DESCRIPTION (provided by applicant): The availability of human genomic information and its variability is allowing researchers to identify the genetic variations responsible for patients' different responses to treatment.1-3 In order to deliver the benefits of personalized medicine to the clinical practice, it is necessary to have accurate genotyping techniques capable of determining multiple genetic markers. The existing Food and Drug Administration (FDA)-approved pharmacogenetics tests require long processing times or have limited multiplexability. Here, we propose the development of rapid and multiplex pharmacogenetic tests based on Twist-Biosensor technology. Twist-Biosensor is a novel microarray technology for oligonucleotide detection based on single molecule DNA hybridization and supercoiling. In this technique, the hybridized targets are subjected to disrupting torsional stress which allows for rapid detection of multiple Single Nucleotide Polymorphisms (SNPs) with extremely low background noise using a simple device. Our overall aim is to demonstrate that devices based on the Twist-Biosensor technology can make personalized medicine more readily available to patients by genotyping several SNPs in a single chip within three hours from sample to results. Our approach will be to build and characterize a prototype device able to genotype three SNPs of the CYP2D6 gene, which is the most prevalent genomic biomarker found on drug labels. About 13% of patients in the U.S. receive prescription drugs metabolized by the CYP2D6 enzyme.4 Aim 1 focuses on fast detection of a single CYP2D6 mutation. Aim 2 focuses on fast multiple CYP2D6 SNP detection in small blood samples.

描述（由申请人提供）：人类基因组信息及其变异性的可用性使研究人员能够识别导致患者对治疗的不同反应的遗传变异。1 -3为了将个性化药物的益处提供给临床实践，有必要拥有能够确定多种遗传标记的准确基因分型技术。现有的食品和药物管理局（FDA）批准的药物遗传学测试需要很长的处理时间或具有有限的多重性。在这里，我们提出了快速和多重药物遗传学测试的基础上扭转生物传感器技术的发展。Twist-Biosensor是一种基于单分子DNA杂交和超螺旋的寡核苷酸检测芯片技术。在该技术中，杂交的靶标经受破坏性扭转应力，这允许使用简单的装置以极低的背景噪声快速检测多个单核苷酸多态性（SNP）。我们的总体目标是证明基于Twist-Biosensor技术的设备可以通过在单个芯片中对几个SNP进行基因分型，在从样本到结果的三个小时内使患者更容易获得个性化药物。我们的方法将是建立和表征一个原型设备，能够对CYP 2D 6基因的三个SNP进行基因分型，这是药物标签上发现的最普遍的基因组生物标志物。美国约有13%的患者接受由CYP 2D 6酶代谢的处方药。4目标1侧重于快速检测单个CYP 2D 6突变。目的2：在少量血液样本中快速检测多种CYP 2D 6 SNP。