Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome

威斯科特-奥尔德里奇综合征的慢病毒基因治疗

基本信息

  • 批准号:
    7463332
  • 负责人:
  • 金额:
    $ 28.6万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-03-01 至 2013-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal seeks to develop an effective and safe pre-clinical model for gene therapy in Wiskott- Aldrich Syndrome (WAS). While transplantation using HLA-matched bone marrow can be curative for young WAS patients, the success rate falls precipitously with increasing age. Multiple lines of evidence document a strong selective advantage for WASP expressing hematopoeitic cell subsets suggesting that introduction of the normal WASP gene into hematopoietic stem cells (HSC) could provide a viable therapeutic alternative in disease management. While conceptually simple, development of a safe and effective strategy for WASP gene replacement requires extensive pre-clinical modeling in human and animal systems. This proposal takes advantage of combined expertise, and a network of important research and clinical collaborators, to establish a lentiviral delivery system for the definitive genetic treatment of WAS. We will test the hypotheses that: 1) WASP activity is crucial for both the generation of marginal zone (MZ) B cells and homeostasis of functional T-regulatory cells (TR); and that these observations help to explain the susceptibility to infection with encapsulated bacteria, and the high-incidence of autoimmunity in WAS patients, respectively. Further, we predict that LV gene therapy will rescue these key defects. 2) Lentiviral vectors containing a pan-hematopoeitic or selected lymphoid restricted promoters will lead to functional correction of lymphoid development, activation, and survival; platelet turnover; and immune function in vivo in an animal model of WAS. 3) Analysis of viral marking and expression in a non-human primate model will allow us to define the optimal vector for use in human clinical trials; and provide key data with regard to any potential toxicity of this vector and/or dysregulated WASP expression within HSC and their progeny. Our proposed studies will provide nearly all of the key expression, efficacy, and safety data required to move forward with a human gene therapy trial for WAS; and have a very high likelihood for translation into new therapies.
描述(由申请人提供):

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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David J Rawlings其他文献

Partially Mismatched Cord Blood Transplantation In X-Linked Immunodeficiencies • 44
部分不匹配的脐带血移植在 X 连锁免疫缺陷病中的应用•44
  • DOI:
    10.1203/00006450-199804001-00065
  • 发表时间:
    1998-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    E Richard Stiehm;Ulrike Ziegner;Sunisa Dovat;Mary Wakim;Maria Garcia-Lloret;Hans Ochs;Kerry Gallagher;Thomas Gross;David J Rawlings;Robert L Roberts;Stephen A Feig
  • 通讯作者:
    Stephen A Feig
An exemplum of XLA.
XLA 的一个例子。
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    8.6
  • 作者:
    L. Notarangelo;David J Rawlings;K. Sullivan
  • 通讯作者:
    K. Sullivan

David J Rawlings的其他文献

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{{ truncateString('David J Rawlings', 18)}}的其他基金

An integrated strategy to define the functional and synergistic impact of T1D causal variants
定义 T1D 因果变异的功能和协同影响的综合策略
  • 批准号:
    9227381
  • 财政年份:
    2016
  • 资助金额:
    $ 28.6万
  • 项目类别:
Lentiviral Gene Therapy of X-Linked Agammaglobulinemia
X连锁无丙种球蛋白血症的慢病毒基因治疗
  • 批准号:
    8825754
  • 财政年份:
    2014
  • 资助金额:
    $ 28.6万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8278876
  • 财政年份:
    2012
  • 资助金额:
    $ 28.6万
  • 项目类别:
Pre-clinical Modeling of Foamy Viral gene Therapy for Murine and Human SCID-X1
小鼠和人类 SCID-X1 泡沫病毒基因治疗的临床前模型
  • 批准号:
    8278864
  • 财政年份:
    2012
  • 资助金额:
    $ 28.6万
  • 项目类别:
B cell function and phenotype as predictors of therapeutic response to rituximab
B 细胞功能和表型作为利妥昔单抗治疗反应的预测因子
  • 批准号:
    8044994
  • 财政年份:
    2010
  • 资助金额:
    $ 28.6万
  • 项目类别:
Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
威斯科特-奥尔德里奇综合征的慢病毒基因治疗
  • 批准号:
    7576150
  • 财政年份:
    2008
  • 资助金额:
    $ 28.6万
  • 项目类别:
Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
威斯科特-奥尔德里奇综合征的慢病毒基因治疗
  • 批准号:
    8228037
  • 财政年份:
    2008
  • 资助金额:
    $ 28.6万
  • 项目类别:
Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
威斯科特-奥尔德里奇综合征的慢病毒基因治疗
  • 批准号:
    7772315
  • 财政年份:
    2008
  • 资助金额:
    $ 28.6万
  • 项目类别:
Lentiviral Gene Therapy for Wiskott-Aldrich Syndrome
威斯科特-奥尔德里奇综合征的慢病毒基因治疗
  • 批准号:
    8029506
  • 财政年份:
    2008
  • 资助金额:
    $ 28.6万
  • 项目类别:
Interdisciplinary Training in Genome Engineering (Component 10 of 11)TL1
基因组工程跨学科培训(第 10 部分,共 11 部分)TL1
  • 批准号:
    7503426
  • 财政年份:
    2007
  • 资助金额:
    $ 28.6万
  • 项目类别:
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