Editing Alveolar Progenitor Cells for Correction of Monogenic Disease

编辑肺泡祖细胞以纠正单基因疾病

基本信息

  • 批准号:
    10198995
  • 负责人:
  • 金额:
    $ 125.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-09-23 至 2023-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Interstitial Lung Diseases (ILDs), represent a large group of chronic pulmonary disorders that are common causes of morbidity and mortality of both children and adults worldwide. Alveolar dysfunction, pulmonary fibrosis, and vascular remodeling associated with chronic ILDs lead to progressive respiratory failure for which they are few effective therapies. Both genetic and environmental factors underlie the pathogenesis of ILDs; including smoking, air pollution, and chronic inflammation and genetic disorders. Mutations in genes regulating surfactant homeostasis or alveolar type 2 (AT2) cell function or survival includes ABCA3, SFTPB, SFTPC, SFTPA, Telomerase (and related genes) that cause respiratory failure in neonates, children, and older individuals. Our PCTC Consortium seeks to develop novel strategies designed to use CRISPR/CAS9 gene editing for lung progenitor cells for correction of a prototypic Childhood Interstitial Lung Diseases (CHILD) disorder that disrupts pulmonary surfactant homeostasis (ABCA3 deficiency) that leads to fatal infantile lung disease. Mutations in in the ABCA3 gene disrupts surfactant lipid and protein production gene causing severe respiratory dysfunction after birth or chronic lung disease in infancy. We will apply CRISPR/CAS9 mediated gene editing to correct ABCA3 in alveolar progenitor cells as disease targets applicable to other genetic and acquired disorders affecting AT2 cells and their progenitors. The identification, targeting and gene editing of alveolar AT2 cells and their progenitors will be widely applicable for the treatment of both genetic and acquired diseases of the peripheral lung in the future.
项目摘要 间质性肺疾病(ILD)代表一大组慢性肺部疾病, 是全世界儿童和成人发病和死亡的共同原因。肺泡功能障碍, 肺纤维化和与慢性ILD相关的血管重塑导致进行性呼吸道疾病, 失败,他们是很少有效的治疗方法。遗传和环境因素都是导致 ILD的发病机制;包括吸烟、空气污染、慢性炎症和遗传性疾病。 调节表面活性物质稳态或肺泡2型(AT 2)细胞功能或存活的基因突变包括 引起新生儿呼吸衰竭的ABCA 3、SFTPB、SFTPC、SFTPA、端粒酶(及相关基因), 儿童和老年人。我们的PCTC联盟寻求开发新的策略, CRISPR/CAS9基因编辑肺祖细胞以纠正原型儿童间质性肺 疾病(儿童):破坏肺表面活性物质稳态(ABCA 3缺乏症),导致 致命的婴儿肺病ABCA 3基因突变破坏表面活性剂脂质和蛋白质的产生 基因导致出生后严重呼吸功能障碍或婴儿期慢性肺病。我们将应用 CRISPR/CAS9介导的基因编辑以纠正肺泡祖细胞中的ABCA 3作为疾病靶点 适用于影响AT 2细胞及其祖细胞的其他遗传性和获得性疾病。身份证明, 肺泡AT 2细胞及其祖细胞的靶向和基因编辑将广泛适用于治疗 遗传性和获得性周围性肺疾病的研究。

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Darrell N. Kotton其他文献

Patient-Specific Inducible Pluripotent Stem Cells Reveal Mechanism of Personalized Therapy for an Inherited Cardiac Arrhythmia
  • DOI:
    10.1016/j.bpj.2011.11.2947
  • 发表时间:
    2012-01-31
  • 期刊:
  • 影响因子:
  • 作者:
    Kai Wang;Cecile Terrenoire;Kevin J. Sampson;Vivek Lyer;Kelvin W. Chan Tung;Jonathan Lu;Wendy Chung;Robert H. Pass;Gordon Keller;Darrell N. Kotton;Robert S. Kass
  • 通讯作者:
    Robert S. Kass
Derivation of transplantable human thyroid follicular epithelial cells from induced pluripotent stem cells
  • DOI:
    10.1016/j.stemcr.2024.10.004
  • 发表时间:
    2024-12-10
  • 期刊:
  • 影响因子:
  • 作者:
    Hendrik J. Undeutsch;Alberto Posabella;Andrea B. Alber;Pushpinder S. Bawa;Carlos Villacorta-Martin;Feiya Wang;Laertis Ikonomou;Darrell N. Kotton;Anthony N. Hollenberg
  • 通讯作者:
    Anthony N. Hollenberg
The COPD GWAS gene emADGRG6/em instructs function and injury response in human iPSC-derived type II alveolar epithelial cells
慢性阻塞性肺疾病全基因组关联研究基因 emADGRG6/em 指导人诱导多能干细胞来源的 II 型肺泡上皮细胞的功能和损伤反应
  • DOI:
    10.1016/j.ajhg.2023.08.017
  • 发表时间:
    2023-10-05
  • 期刊:
  • 影响因子:
    8.100
  • 作者:
    Rhiannon B. Werder;Kayleigh A. Berthiaume;Carly Merritt;Marissa Gallagher;Carlos Villacorta-Martin;Feiya Wang;Pushpinder Bawa;Vidhi Malik;Shawn M. Lyons;Maria C. Basil;Edward E. Morrisey;Darrell N. Kotton;Xiaobo Zhou;Michael H. Cho;Andrew A. Wilson
  • 通讯作者:
    Andrew A. Wilson
Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels
新生基质沉积有助于在合成水凝胶中由聚集体形成肺泡类器官
  • DOI:
    10.1016/j.stemcr.2024.11.006
  • 发表时间:
    2025-01-14
  • 期刊:
  • 影响因子:
    5.100
  • 作者:
    Madeline K. Eiken;Charlie J. Childs;Lindy K. Brastrom;Tristan Frum;Eleanor M. Plaster;Donia W. Ahmed;Ryan C. Spencer;Orren Shachaf;Suzanne Pfeiffer;Justin E. Levine;Konstantinos-Dionysios Alysandratos;Darrell N. Kotton;Jason R. Spence;Claudia Loebel
  • 通讯作者:
    Claudia Loebel
Lung stem cells
  • DOI:
    10.1007/s00441-007-0479-2
  • 发表时间:
    2007-09-06
  • 期刊:
  • 影响因子:
    2.900
  • 作者:
    Darrell N. Kotton;Alan Fine
  • 通讯作者:
    Alan Fine

Darrell N. Kotton的其他文献

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{{ truncateString('Darrell N. Kotton', 18)}}的其他基金

Developing a patient-specific organoid model of pulmonary fibrosis using iPSCs
使用 iPSC 开发患者特异性肺纤维化类器官模型
  • 批准号:
    10026360
  • 财政年份:
    2020
  • 资助金额:
    $ 125.83万
  • 项目类别:
Developing a patient-specific organoid model of pulmonary fibrosis using iPSCs
使用 iPSC 开发患者特异性肺纤维化类器官模型
  • 批准号:
    10318560
  • 财政年份:
    2020
  • 资助金额:
    $ 125.83万
  • 项目类别:
Developing a patient-specific organoid model of pulmonary fibrosis using iPSCs
使用 iPSC 开发患者特异性肺纤维化类器官模型
  • 批准号:
    10525231
  • 财政年份:
    2020
  • 资助金额:
    $ 125.83万
  • 项目类别:
Editing Alveolar Progenitor Cells for Correction of Monogenic Disease
编辑肺泡祖细胞以纠正单基因疾病
  • 批准号:
    10417109
  • 财政年份:
    2016
  • 资助金额:
    $ 125.83万
  • 项目类别:
NRSA Training Core
NRSA 培训核心
  • 批准号:
    10615243
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:
Epigenenomic and transcriptomic networks in normal and defective lung development
正常和有缺陷的肺发育中的表观基因组和转录组网络
  • 批准号:
    9144829
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:
NRSA Training Core
NRSA 培训核心
  • 批准号:
    10400208
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:
Epigenenomic and transcriptomic networks in normal and defective lung development
正常和有缺陷的肺发育中的表观基因组和转录组网络
  • 批准号:
    8927909
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:
Boston University Clinical and Translational Science Institute
波士顿大学临床与转化科学研究所
  • 批准号:
    9261614
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:
Boston University Clinical and Translational Science Institute
波士顿大学临床与转化科学研究所
  • 批准号:
    9126634
  • 财政年份:
    2015
  • 资助金额:
    $ 125.83万
  • 项目类别:

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