Human Parvovirus B19 Vectors: Mechanism of Transduction
人类细小病毒 B19 载体:转导机制
基本信息
- 批准号:7178444
- 负责人:
- 金额:$ 34.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-03-01 至 2009-02-28
- 项目状态:已结题
- 来源:
- 关键词:AdenovirusesAntigensAttentionBindingBiologyBlood typing procedureBone MarrowCapsidCell CommunicationCell Surface ReceptorsCell surfaceCellsClinical TrialsDataDependovirusDevelopmentDiseaseElementsErythrocytesErythroidErythroid CellsErythroid Progenitor CellsGene ExpressionGenomeHematopoieticHematopoietic SystemHematopoietic stem cellsHemoglobinopathiesHumanHuman Parvovirus B19HybridsInfectionIntegrin alpha5beta1IntegrinsKnowledgeLeadLightLiteratureMapsMediatingModelingMolecularNatureNumbersParvovirusPhaseProtocols documentationPublishingRangeRecombinant adeno-associated virus (rAAV)RecombinantsResearch PersonnelRetroviridaeSickle Cell AnemiaSignal TransductionSingle Stranded DNA VirusSpecificitySystemTechniquesTestingThalassemiaTranscendTranscriptional RegulationTransgenic MiceTropismVertebratesViralVirusVirus Receptorsbaseblood groupcell typegene therapygene transfer vectorimprovednovelnovel strategiesprogenitorpromotertissue tropismtranscription factortransgene expressionvector
项目摘要
DESCRIPTION (provided by applicant): Parvoviruses constitute a unique group of small, single-stranded DNA viruses that infect all vertebrates. One of the non-pathogenic human parvovirus, the adeno-associated virus 2 (AAV) has gained attention as a useful alternative to the more commonly used retrovirus- and adenovirus-based vectors in human gene therapy. In contrast to AAV, which possesses a broad host-range, the pathogenic human parvovirus B19 has been shown to have a remarkably narrow tissue-tropism for erythroid progenitor cells presumably because the virus uses the blood group P antigen as a cell surface receptor. We have developed recombinant human parvovirus B19 vectors in which recombinant AAV genomes are encapsidated in parvovirus B19 capsids. Although the viral titers obtained are low, using these hybrid vectors, we have demonstrated that P antigen alone is not sufficient to impart erythroid cell-specificity to parvovirus B19. We have proposed a "triple level of erythroid-specificity" model for parvovirus B19 infection in which P antigen is utilized as a primary receptor for virus binding, activated alpha5beta1 integrin as a cell surface co-receptor for viral entry, and a hitherto unknown cellular transcription factor for erythroid cell-specific expression from the viral promoter at map unit 6 (B19p6). Using a variety of molecular techniques and recombinant parvovirus vectors, we will test the following hypotheses: 1. The inclusion of appropriate transcriptional control elements and parvovirus B19 "packaging signal" wilt lead to improved titers of recombinant parvovirus B19 vectors; 2. Mature RBCs are utilized for systemic dissemination and efficient entry of parvovirus B19 into primary human hematopoietic cells in the erythroid lineage, and 3. A putative transcription factor, which is present only in primary human erythroid progenitor cells, mediates lineage-restricted gene expression from the parvovirus B19p6 promoter. The following three Specific Aims will be pursued: 1. Development of strategies to generate high-titer recombinant parvovirus B19 vectors. 2. Elucidation of underlying mechanisms of parvovirus B19 infection of primary human erythroid progenitor ceils. 3. Elucidation of recombinant parvovirus vector-mediated transduction of primary human hematopoietic stem cells and erythroid lineage-restricted gene expression, and characterization of the putative cellular transcription factor specific for the B19p6 promoter. The knowledge gained from these studies will shed light on parvovirus Bl9-host cell interactions, and will lead to further improvements in recombinant parvovirus B19 vectors for their potential use in human gene therapy.
描述(由申请方提供):细小病毒是一组独特的小单链DNA病毒,可感染所有脊椎动物。腺相关病毒2(腺相关病毒2)是一种非致病性人类细小病毒,作为人类基因治疗中更常用的逆转录病毒和腺病毒载体的有用替代品而受到关注。与具有广泛宿主范围的AAV相反,致病性人细小病毒B19已显示对红系祖细胞具有非常窄的组织嗜性,这大概是因为病毒使用血型P抗原作为细胞表面受体。我们已经开发了重组人细小病毒B19载体,其中重组AAV基因组被包裹在细小病毒B19衣壳中。虽然获得的病毒滴度低,使用这些杂合载体,我们已经证明,单独的P抗原是不足以赋予细小病毒B19的红系细胞特异性。我们已经提出了一个“三重水平的红细胞特异性”模型的细小病毒B19感染,其中P抗原被用作病毒结合的主要受体,激活的α 5 β 1整合素作为细胞表面的辅助受体的病毒进入,和迄今未知的细胞转录因子的红细胞特异性表达的病毒启动子在地图单位6(B19 p6)。利用各种分子技术和重组细小病毒载体,我们将测试以下假设:1。包含适当的转录控制元件和细小病毒B19“包装信号”将导致重组细小病毒B19载体的改进的滴度; 2.成熟的RBC用于系统传播和细小病毒B19有效进入红系中的原代人造血细胞,和3.一个假定的转录因子,这是目前只在原代人类红系祖细胞,介导的谱系限制性基因表达的细小病毒B19 p6启动子。将实现以下三个具体目标:1.开发产生高滴度重组细小病毒B19载体的策略。2.阐明细小病毒B19感染原代人红系祖细胞的潜在机制。3.重组细小病毒载体介导的原代人造血干细胞转导和红系限制性基因表达的阐明,以及对B19 p6启动子特异性的推定细胞转录因子的表征。从这些研究中获得的知识将揭示细小病毒B19-宿主细胞相互作用,并将导致重组细小病毒B19载体的进一步改进,以用于其在人类基因治疗中的潜在用途。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Arun Srivastava其他文献
Arun Srivastava的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Arun Srivastava', 18)}}的其他基金
Mechanism of Hepatocyte Transduction by AAV Vectors
AAV 载体转导肝细胞的机制
- 批准号:
7489003 - 财政年份:2007
- 资助金额:
$ 34.49万 - 项目类别:
Mechanism of Hepatocyte Transduction by AAV Vectors
AAV 载体转导肝细胞的机制
- 批准号:
7017369 - 财政年份:2005
- 资助金额:
$ 34.49万 - 项目类别:
Human Parvovirus B19 Vectors: Mechanism of Transduction
人类细小病毒 B19 载体:转导机制
- 批准号:
7024569 - 财政年份:2004
- 资助金额:
$ 34.49万 - 项目类别:
Human Parvovirus B19 Vectors: Mechanism of Transduction
人类细小病毒 B19 载体:转导机制
- 批准号:
6855770 - 财政年份:2004
- 资助金额:
$ 34.49万 - 项目类别:
Human Parvovirus B19 Vectors: Mechanism of Transduction
人类细小病毒 B19 载体:转导机制
- 批准号:
7391091 - 财政年份:2004
- 资助金额:
$ 34.49万 - 项目类别:
Human Parvovirus B19 Vectors: Mechanism of Transduction
人类细小病毒 B19 载体:转导机制
- 批准号:
6927575 - 财政年份:2004
- 资助金额:
$ 34.49万 - 项目类别:
Hematepoietic Stem Cell Transduction by AAV2 Vectors
AAV2 载体的造血干细胞转导
- 批准号:
6337984 - 财政年份:2001
- 资助金额:
$ 34.49万 - 项目类别:
Hematepoietic Stem Cell Transduction by AAV2 Vectors
AAV2 载体的造血干细胞转导
- 批准号:
6746916 - 财政年份:2001
- 资助金额:
$ 34.49万 - 项目类别:
Hematepoietic Stem Cell Transduction by AAV2 Vectors
AAV2 载体的造血干细胞转导
- 批准号:
6638693 - 财政年份:2001
- 资助金额:
$ 34.49万 - 项目类别:
相似国自然基金
Neo-antigens暴露对肾移植术后体液性排斥反应的影响及其机制研究
- 批准号:2022J011295
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
结核分枝杆菌持续感染期抗原(latency antigens)的重组BCG疫苗研究
- 批准号:30801055
- 批准年份:2008
- 资助金额:19.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Bovine herpesvirus 4 as a vaccine platform for African swine fever virus antigens in pigs
牛疱疹病毒 4 作为猪非洲猪瘟病毒抗原的疫苗平台
- 批准号:
BB/Y006224/1 - 财政年份:2024
- 资助金额:
$ 34.49万 - 项目类别:
Research Grant
Uncovering tumor specific antigens and vulnerabilities in ETP-acute lymphoblastic leukemia
揭示 ETP-急性淋巴细胞白血病的肿瘤特异性抗原和脆弱性
- 批准号:
480030 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Operating Grants
A novel vaccine approach combining mosquito salivary antigens and viral antigens to protect against Zika, chikungunya and other arboviral infections.
一种结合蚊子唾液抗原和病毒抗原的新型疫苗方法,可预防寨卡病毒、基孔肯雅热和其他虫媒病毒感染。
- 批准号:
10083718 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Small Business Research Initiative
Regulation of B cell responses to vaccines by long-term retention of antigens in germinal centres
通过在生发中心长期保留抗原来调节 B 细胞对疫苗的反应
- 批准号:
MR/X009254/1 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Research Grant
Adaptive Discrimination of Risk of Antigens in Immune Memory Dynamics
免疫记忆动态中抗原风险的适应性辨别
- 批准号:
22KJ1758 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Grant-in-Aid for JSPS Fellows
22-ICRAD Call 2 - Improving the diagnosis of tuberculosis in domestic ruminants through the use of new antigens and test platforms
22-ICRAD 呼吁 2 - 通过使用新抗原和测试平台改善家养反刍动物结核病的诊断
- 批准号:
BB/Y000927/1 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Research Grant
Protective immunity elicited by distinct polysaccharide antigens of classical and hypervirulent Klebsiella
经典和高毒力克雷伯氏菌的不同多糖抗原引发的保护性免疫
- 批准号:
10795212 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Integrative proteome analysis to harness humoral immune response against tumor antigens
综合蛋白质组分析利用针对肿瘤抗原的体液免疫反应
- 批准号:
23K18249 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Functionally distinct human CD4 T cell responses to novel evolutionarily selected M. tuberculosis antigens
功能独特的人类 CD4 T 细胞对新型进化选择的结核分枝杆菌抗原的反应
- 批准号:
10735075 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别:
Targeting T3SA proteins as protective antigens against Yersinia
将 T3SA 蛋白作为针对耶尔森氏菌的保护性抗原
- 批准号:
10645989 - 财政年份:2023
- 资助金额:
$ 34.49万 - 项目类别: