Vector Integration and Tracking

矢量积分和跟踪

基本信息

  • 批准号:
    8278891
  • 负责人:
  • 金额:
    $ 48.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-08-07 至 2017-07-31
  • 项目状态:
    已结题

项目摘要

The development of leukemia has been observed in 5 out of 19 SCID-Xl pafients treated by stem cell gene therapy. In all 5 pafients the development of leukemia was due to insertional mutagenesis, i.e. the retrovirus- mediated activafion of nearby proto-oncogenes. Thus, the careful study of integration sites and the contribufion of individual clones to repopulafion will be of crucial importance for all gene therapy studies, and the FDA has mandated the careful monitoring of retroviral integration sites in all clinical gene therapy studies. The Vector Integration and Tracking Core D will provide all projects a centralized facility to efficiently identify foamy virus (FV) vector integrafion sites in complex biological DNA samples from in vitro or in vivo studies. We will use recenfiy developed improved non-restricfion (nr)LAM-PCR. The core will be able to process a variety of samples from murine, dog, or human to generate DNA for shuttle vector or PCR- based methods. For nrLAM-PCR, as little as lOng of DNA can be used to carry out FV vector integrafion site amplificafion and extended processing in preparation for sequencing. The samples processed by Core D will be compafible with both Sanger-based sequencing for pilot experiments and new sequencing methodologies, such as pyrosequencing, for deep sequencing to identify all of the amplifiable FV vector integration sites in a given sample. Core D will also provide assistance to all projects to design primers specific to FV vector integrafion sites to allow for DNA-based real time (RT)-PCR tracking to assess the contribufion for individual clones that are deemed important for further invesfigation. In addifion, Core D will provide a centralized facility to analyze integrafion sites via a common gateway interface (CGI)-PERL web server. Current versions of the human (hg19), dog (canFam2) and mouse (mm9) genomes will be supported. The Core will also provide support to investigators through PERL programs to correlate FV vector integration sites with data from published databases including proto-oncogene TSS, microarray data and over- represented gene classes. The bioinformatics component will also generate random datasets for all three genomes, human, mouse and dog, to evaluate over-represented gene classes near vector proviruses. RELEVANCE: The focus of this PPG is to test the efficacy and safety of the most appropriate retrovirus vector system, FV vectors for the treatment of SCID-Xl. An indispensible aspect of retrovirus-based safety analysis is integration site profiling and characterization of the surrounding genomic elements. The specific aims of Core D will provide a careful standardized approach defining the safety of the current and improved FV vectors developed in Projects 1-3.
在19例接受干细胞基因治疗的SCID-Xl患者中,有5例发生了白血病

项目成果

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专利数量(0)

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BRIAN C BEARD其他文献

BRIAN C BEARD的其他文献

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{{ truncateString('BRIAN C BEARD', 18)}}的其他基金

Development and Safety Evaluation of Chemo-Protective Gene Therapy Vectors
化学保护性基因治疗载体的开发和安全性评价
  • 批准号:
    8136048
  • 财政年份:
    2007
  • 资助金额:
    $ 48.97万
  • 项目类别:
Development and Safety Evaluation of Chemo-Protective Gene Therapy Vectors
化学保护性基因治疗载体的开发和安全性评价
  • 批准号:
    7318585
  • 财政年份:
    2007
  • 资助金额:
    $ 48.97万
  • 项目类别:
Development and Safety Evaluation of Chemo-Protective Gene Therapy Vectors
化学保护性基因治疗载体的开发和安全性评价
  • 批准号:
    7497056
  • 财政年份:
    2007
  • 资助金额:
    $ 48.97万
  • 项目类别:
Development and Safety Evaluation of Chemo-Protective Gene Therapy Vectors
化学保护性基因治疗载体的开发和安全性评价
  • 批准号:
    7681219
  • 财政年份:
    2007
  • 资助金额:
    $ 48.97万
  • 项目类别:
Development and Safety Evaluation of Chemo-Protective Gene Therapy Vectors
化学保护性基因治疗载体的开发和安全性评价
  • 批准号:
    7905203
  • 财政年份:
    2007
  • 资助金额:
    $ 48.97万
  • 项目类别:
Vector Integration and Tracking
矢量积分和跟踪
  • 批准号:
    8567347
  • 财政年份:
  • 资助金额:
    $ 48.97万
  • 项目类别:
Vector Integration and Tracking
矢量积分和跟踪
  • 批准号:
    8712355
  • 财政年份:
  • 资助金额:
    $ 48.97万
  • 项目类别:
Vector Integration and Tracking
矢量积分和跟踪
  • 批准号:
    9117270
  • 财政年份:
  • 资助金额:
    $ 48.97万
  • 项目类别:
Vector Integration and Tracking
矢量积分和跟踪
  • 批准号:
    8897250
  • 财政年份:
  • 资助金额:
    $ 48.97万
  • 项目类别:

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