Development of AAV vectors for CF therapy

用于 CF 治疗的 AAV 载体的开发

基本信息

  • 批准号:
    10544549
  • 负责人:
  • 金额:
    $ 38.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-12-15 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

Abstract Cystic fibrosis (CF) is caused by mutations of the CF transmembrane conductance regulator (CFTR) gene. Airway disease is the leading cause of morbidity and mortality. Gene therapy offers a potential cure for CF. Among gene delivery vehicles, adeno-associated virus (AAV) vectors have demonstrated success in clinical trials. AAV vectors have also been tested in CF patients via airway delivery for gene addition but without measurable success perhaps due to physical airway barriers and inefficient transduction. Studies have shown that higher AAV transduction of airway epithelial cells occur via the basolateral membrane in vitro and our preliminary study demonstrated that systemic administration of AAV vectors induced much more efficient lung transduction than airway delivery in mice. These findings strongly suggest that AAV can transduce airway epithelial cells via systemic administration. The efficiency of AAV transduction in airway epithelial cells after systemic delivery of AAV vectors is usually restricted by the blood vascular barrier and a high prevalence of AAV neutralizing antibodies (Nabs). In this proposal, based on our previous studies, we will explore different strategies to develop novel AAV vectors using directed evolution and AAV virion specific binding peptides via phage display technology to increase AAV vector vascular permeability for enhanced transduction in airway epithelial cells and to evade Nabs after systemic administration. Finally, the novel approaches developed in this proposal will be used to deliver optimized CRISPR/Cas9 specific for CFTR del508 to CF mice and study the long-term phenotypic correction. The results generated from these studies will allow us to develop an effective approach to treat CF patients using AAV vector mediated gene delivery. .
摘要

项目成果

期刊论文数量(0)
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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Chengwen Li其他文献

Chengwen Li的其他文献

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{{ truncateString('Chengwen Li', 18)}}的其他基金

Novel strategy to block Nabs for AAV gene delivery
阻断 Nabs 进行 AAV 基因传递的新策略
  • 批准号:
    10570881
  • 财政年份:
    2022
  • 资助金额:
    $ 38.88万
  • 项目类别:
Novel strategy to block Nabs for AAV gene delivery
阻断 Nabs 进行 AAV 基因传递的新策略
  • 批准号:
    10416627
  • 财政年份:
    2022
  • 资助金额:
    $ 38.88万
  • 项目类别:
Rational design of AAV vectors with human hepatocyte tropism and neutralizing antibody evasion
具有人肝细胞趋向性和中和抗体逃避性的AAV载体的合理设计
  • 批准号:
    10546241
  • 财政年份:
    2022
  • 资助金额:
    $ 38.88万
  • 项目类别:
Development of AAV vectors for CF therapy
用于 CF 治疗的 AAV 载体的开发
  • 批准号:
    10117463
  • 财政年份:
    2020
  • 资助金额:
    $ 38.88万
  • 项目类别:
Develop humanized AAV vectors for liver targeting and neutralizing antibody evasion
开发用于肝脏靶向和中和抗体逃避的人源化 AAV 载体
  • 批准号:
    10079155
  • 财政年份:
    2020
  • 资助金额:
    $ 38.88万
  • 项目类别:
Development of AAV vectors for CF therapy
用于 CF 治疗的 AAV 载体的开发
  • 批准号:
    10319017
  • 财政年份:
    2020
  • 资助金额:
    $ 38.88万
  • 项目类别:
Novel strategy to block AAV neutralizing anitbody activity
阻止 AAV 中和抗体活性的新策略
  • 批准号:
    10080225
  • 财政年份:
    2020
  • 资助金额:
    $ 38.88万
  • 项目类别:
Optimization of AAV vector to deliver FVa for hemophilia with inhibitors
优化 AAV 载体以通过抑制剂递送血友病 FVa
  • 批准号:
    10372097
  • 财政年份:
    2019
  • 资助金额:
    $ 38.88万
  • 项目类别:
Enhance AAV Liver Transduction with Capsid Immune Evasion
通过衣壳免疫逃避增强 AAV 肝脏转导
  • 批准号:
    9098885
  • 财政年份:
    2016
  • 资助金额:
    $ 38.88万
  • 项目类别:
Enhance AAV Liver Transduction with Capsid Immune Evasion
通过衣壳免疫逃避增强 AAV 肝脏转导
  • 批准号:
    9893176
  • 财政年份:
    2016
  • 资助金额:
    $ 38.88万
  • 项目类别:

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  • 财政年份:
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