Renewable antibodies to secreted proteins and single and multi-pass cell surface

针对分泌蛋白以及单次和多次细胞表面的可再生抗体

基本信息

  • 批准号:
    8702409
  • 负责人:
  • 金额:
    $ 40.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-24 至 2019-08-31
  • 项目状态:
    已结题

项目摘要

Antibodies for research and therapy Antibodies (Abs) are essential reagents for determining how proteins function under normal or pathophysiological conditions. Uses include quantifying proteins, identifying the temporal and spatial pattern of expression in cells and tissue, and identifying interacting partners. Such studies require Abs of high specificity that function in assays including Western blotting, immunoprecipitation, immunohistochemistry (IHC) and in vivo imaging. Over half the human proteome is not annotated, and functional Abs are not reliably available for these proteins. Where monoclonal or polyclonal Abs are commercially available, a high proportion show either poor specificity or fail to recognize their targets (1-5). For example, a recent editorial by Michel et al. highlighted the lack of target specificity for 49 Abs against 19 subtypes of GPCRs (6). An additional problem is lot-to-lot variability in Ab specificity, including monoclonal Abs (mAbs) made via hybridoma technology, resulting in inconsistent assay results (4). The purpose of TR&D Project One is to develop high throughput scalable technologies to generate widely available, renewable, validated and standardized sets of Ab reagents (rAbs) to a portion of the secretome consisting of plasma membrane and extracellular proteins. One key aspect of the technology that will be developed is that where possible, the expensive, time consuming and tedious task of antigen generation and purification will be bypassed by displaying the antigen at high levels on the surface of eukaryotic cells, including yeast, and mammalian cell lines. Antigens expressed on mammalian cells or yeast will be used for selection of phage Abs, as well as for validation and characterization. The use of phage display bypasses the low throughput, time consuming, and expensive immunization of animals to generate polyclonal Abs or the use of hybridoma technology to generate mAbs. Moreover, the Ab genes are cloned, the rAbs are forever renewable and can easily be formatted for expression as Ab fragments or traditional mAbs with any Fc. While we will primarily generate rAbs to a subset of the secretome in this Project (the extracellular portions of plasma membrane and extracellular proteins), this approach should be applicable to many or all of the secreted proteins, 20-40% of the proteome.
用于研究和治疗的抗体抗体(Abs)是确定蛋白质在正常或病理生理条件下如何发挥作用的基本试剂。用途包括定量蛋白质,识别细胞和组织中表达的时间和空间模式,以及识别相互作用的伙伴。此类研究需要具有高特异性的抗体,能够在Western blotting、免疫沉淀、免疫组织化学(IHC)和体内成像等检测中发挥作用。超过一半的人类蛋白质组没有被注释,而且这些蛋白质的功能性抗体也不可靠。在市面上可以买到的单克隆或多克隆抗体中,有很大一部分要么特异性差,要么不能识别它们的靶标(1-5)。例如,Michel等人最近的一篇社论强调了49种抗体对19种gpcr亚型缺乏靶向特异性(6)。另一个问题是,包括通过杂交瘤技术制备的单克隆抗体(mab)在内,抗体特异性的批次间可变性导致检测结果不一致(4)。

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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James D. Marks其他文献

Predictors of All-Cause 30-Day Readmissions in Patients with Heart Failure at an Urban Safety Net Hospital: The Importance of Social Determinants of Health and Mental Health
  • DOI:
    10.1016/j.ajmo.2023.100060
  • 发表时间:
    2023-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Alexandra B. Steverson;Paul J. Marano;Caren Chen;Yifei Ma;Rachel J. Stern;Jean Feng;Efstathios D. Gennatas;James D. Marks;Matthew S. Durstenfeld;Jonathan D. Davis;Priscilla Y. Hsue;Lucas S. Zier
  • 通讯作者:
    Lucas S. Zier
Factors affecting perioperative pulmonary function in acute respiratory failure.
急性呼吸衰竭围手术期肺功能影响因素
  • DOI:
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    9.6
  • 作者:
    Diane R. Biery;Diane R. Biery;James D. Marks;James D. Marks;A. Schapera;A. Schapera;M. Autry;M. Autry;R. M. Schlobohm;R. M. Schlobohm;Jeffrey A. Katz;Jeffrey A. Katz
  • 通讯作者:
    Jeffrey A. Katz
Mass spectral analysis of a protein complex using single-chain antibodies selected on a peptide target: applications to functional genomics.
使用针对肽靶标选择的单链抗体对蛋白质复合物进行质谱分析:在功能基因组学中的应用。
  • DOI:
    10.1006/jmbi.2000.4070
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    5.6
  • 作者:
    Robert W. Siegel;Beth Allen;P. Pavlík;James D. Marks;Andrew Bradbury;Andrew Bradbury
  • 通讯作者:
    Andrew Bradbury
Internalizing antibodies and targeted cancer therapy: direct selection from phage display libraries.
内化抗体和靶向癌症治疗:从噬菌体展示库中直接选择。

James D. Marks的其他文献

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{{ truncateString('James D. Marks', 18)}}的其他基金

Antibody Research Technology Center
抗体研究技术中心
  • 批准号:
    8666864
  • 财政年份:
    2014
  • 资助金额:
    $ 40.94万
  • 项目类别:
Generation of therapeutic antibodies to serotype F botulism
针对血清型 F 肉毒杆菌中毒的治疗性抗体的产生
  • 批准号:
    8608996
  • 财政年份:
    2013
  • 资助金额:
    $ 40.94万
  • 项目类别:
Generation of therapeutic antibodies to serotype F botulism
针对血清型 F 肉毒杆菌中毒的治疗性抗体的产生
  • 批准号:
    8996674
  • 财政年份:
    2013
  • 资助金额:
    $ 40.94万
  • 项目类别:
Generation of therapeutic antibodies to serotype F botulism
针对血清型 F 肉毒杆菌中毒的治疗性抗体的产生
  • 批准号:
    8790945
  • 财政年份:
    2013
  • 资助金额:
    $ 40.94万
  • 项目类别:
Generation of therapeutic antibodies to serotype F botulism
针对血清型 F 肉毒杆菌中毒的治疗性抗体的产生
  • 批准号:
    8474647
  • 财政年份:
    2013
  • 资助金额:
    $ 40.94万
  • 项目类别:
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapy
用于肉毒杆菌神经毒素中毒治疗的三特异性单克隆抗体
  • 批准号:
    8469825
  • 财政年份:
    2012
  • 资助金额:
    $ 40.94万
  • 项目类别:
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapy
用于肉毒杆菌神经毒素中毒治疗的三特异性单克隆抗体
  • 批准号:
    8367214
  • 财政年份:
    2012
  • 资助金额:
    $ 40.94万
  • 项目类别:
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapy
用于肉毒杆菌神经毒素中毒治疗的三特异性单克隆抗体
  • 批准号:
    8875583
  • 财政年份:
    2012
  • 资助金额:
    $ 40.94万
  • 项目类别:
Trispecific monoclonal antibody for botulinum neurotoxin intoxication therapy
用于肉毒杆菌神经毒素中毒治疗的三特异性单克隆抗体
  • 批准号:
    8839870
  • 财政年份:
    2012
  • 资助金额:
    $ 40.94万
  • 项目类别:
Development of botulinum neurotoxin immunotherapy, serotypes C, D, F, and G
肉毒杆菌神经毒素免疫疗法(血清型 C、D、F 和 G)的开发
  • 批准号:
    8547992
  • 财政年份:
    2012
  • 资助金额:
    $ 40.94万
  • 项目类别:

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阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
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