Novel Strategies for Development of a Multiplexed Test with Expanded Content for Spinal Muscular Atrophy

开发具有扩展内容的脊髓性肌萎缩症多重测试的新策略

基本信息

  • 批准号:
    9909806
  • 负责人:
  • 金额:
    $ 18.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-30 至 2021-08-31
  • 项目状态:
    已结题

项目摘要

Summary The overall goal of this project is to develop a cost-effective multiplexed diagnostic test for spinal muscular atrophy (SMA) to rapidly and accurately analyze multiple classes of disease-causing, disease-modifying DNA variants, and carrier status markers. Ultimately, the proposed test will have a far-reaching impact by expanding the identification and stratification of patients who may benefit from new treatments, and by improving the detection of SMA carriers. The proposed test will detect an expanded panel of variants that are not assessed by conventional testing. The broader content is important because age of onset, disease severity and progression correlations with the nature of the SMN1 mutations, and the compensatory and modifying effects of SMN2 and other genes. The expanded SMA test will not only extend the molecular testing to benefit more prospective parents and patients with atypical symptoms including adult onset cases, but will also address SMA testing needs of underserved populations. The expanded SMA test panel will build upon Asuragen’s AmplideX® PCR/CE SMN1/2 Kit (RUO and CE- IVD) and take advantage of a novel strategy Multiplexed & Efficient Resolution of Genetic Elements (MERGE)- PCR to assess: 1) copy number variants (CNVs) of SMN1 and SMN2, 2) pathogenic mutations in SMN1, 3) disease-modifying mutations, and 4) silent carrier markers. We will also incorporate a novel gene-tagged genotyping strategy to determine whether a mutation is in the SMN1 or SMN2 gene. The specific aims are: Aim 1. Design and optimize individual assays for a unified multiplex MERGE-PCR/CE test to detect multiple classes of disease-causing, disease-modifying DNA variants and carrier markers. Aim 2. Develop algorithms to support assay signal deconvolution and enable accurate genotype classification of CNV, SNV, and INDEL signals from multiple fluorophore channels. Aim 3. Develop and verify a single-tube multiplex PCR-based test. In Phase II, we will advance the technology into a cGMP kit development process, enable market-ready software for automatic variant calling, and develop controls and standards for an in vitro diagnostic product. The project will benefit from Asuragen’s years of experience optimizing multiplexing PCR chemistries to develop and commercialize high-performance diagnostic PCR/CE assays.
总结 该项目的总体目标是开发一种具有成本效益的脊髓肌肉萎缩症的多重诊断测试。 萎缩(SMA),以快速准确地分析多种类型的致病,疾病修饰DNA 变体和携带者状态标记。最终,拟议中的测试将通过扩大 对可能受益于新治疗的患者进行识别和分层,并通过改善 SMA载波的检测。拟议的测试将检测一组扩展的变体,这些变体不是由 常规测试。更广泛的内容是重要的,因为发病年龄,疾病严重程度和进展 与SMN 1突变性质的相关性,以及SMN 2和 其他基因扩展的SMA检测不仅将扩展分子检测, 父母和有非典型症状的患者,包括成人发病病例,但也将解决SMA检测 服务不足人群的需求。 扩展的SMA检测板将建立在Asuragen的AmplideX® PCR/CE SMN 1/2试剂盒(RUO和CE- IVD),并利用一种新的策略多路复用和有效的遗传元件解析(MERGE)- PCR评估:1)SMN 1和SMN 2的拷贝数变体(CNV),2)SMN 1中的致病性突变,3) 疾病修饰突变,和4)沉默携带者标记。我们还将整合一种新的基因标记 基因分型策略,以确定突变是否在SMN 1或SMN 2基因中。具体目标是: 目标1。设计并优化单一检测试剂盒,以实现统一的多重MERGE-PCR/CE检测, 致病、致病修饰DNA变异和携带者标记的种类。 目标二。开发算法以支持检测信号去卷积,并实现对基因型的准确分类。 来自多个荧光团通道的CNV、SNV和INDEL信号。 目标3。开发并验证基于单管多重PCR的检测。 在第二阶段,我们将把该技术推进到cGMP试剂盒开发过程中,使市场准备就绪, 用于自动变异识别软件,以及开发用于体外诊断产品的控制和标准。的 该项目将受益于Asuragen多年来优化多重PCR化学的经验, 商业化高性能诊断PCR/CE检测。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Huiping Zhu其他文献

Huiping Zhu的其他文献

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{{ truncateString('Huiping Zhu', 18)}}的其他基金

Genetic Susceptibility of Neural Tube Defects: Diabetes/Obesity-related Genes
神经管缺陷的遗传易感性:糖尿病/肥胖相关基因
  • 批准号:
    8136806
  • 财政年份:
    2009
  • 资助金额:
    $ 18.24万
  • 项目类别:
Genetic Susceptibility of Neural Tube Defects: Diabetes/Obesity-related Genes
神经管缺陷的遗传易感性:糖尿病/肥胖相关基因
  • 批准号:
    7826729
  • 财政年份:
    2009
  • 资助金额:
    $ 18.24万
  • 项目类别:
Genetic Susceptibility of Neural Tube Defects: Diabetes/Obesity-related Genes
神经管缺陷的遗传易感性:糖尿病/肥胖相关基因
  • 批准号:
    7660839
  • 财政年份:
    2009
  • 资助金额:
    $ 18.24万
  • 项目类别:

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