GOALI: Collaborative Research: Industrial Implementation of Smart Biopolymers for Purification of Biological Products
目标:合作研究:用于生物制品纯化的智能生物聚合物的工业实施
基本信息
- 批准号:1403724
- 负责人:
- 金额:$ 26.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-01 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Karande, Pankaj / Chen, Wilfred 1403697 / 1403724 Rensselaer Polytechnic Institute / University of Delaware The proposed project is a collaboration between industry (Bristol-Myers Squibb) and academia (Rensselaer Polytechnic Institute and University of Delaware) aimed at developing the next generation and state-of-art smart biopolymers system for the purification of protein therapeutics in industrial bioprocessing. There is a significant need and interest in the industry for the development of novel techniques for recovery of biological materials that are advantageous in terms of scale, cost, and ease-of-deployment compared to conventional chromatographic processes. The PIs propose to develop affinity precipitation processes that combine the selectivity of affinity chromatography along with the scalability and cost benefits of precipitation. This project will employ new classes of affinity peptides in concert with efficient smart biopolymers which can be induced to come in and out of solution with minor changes in salt and/or temperature. There is significant interest in the development of non-chromatographic affinity recovery processes for biological products. Affinity precipitation combines the selectivity of affinity chromatography along with the scalability and cost benefits of precipitation. In prior research supported by NSF the PIs have employed Elastin like polypeptides fused to the mAb binding Z domain (ELP-Z) to develop a scalable mAb affinity precipitation method. The proposed work builds upon the previous work to generate entirely new classes of smart biopolymer affinity reagents and evaluate their utility for the industrial purification of mAbs, FCfusions, and non-mAb biologics from inclusion body and pegylation processes. Their practical utility will be evaluated for large-scale protein purification in partnership with Bristol-Myers Squibb (BMS). This research will result in a flexible platform for large-scale purification of biological products. The first component of the proposed project will be a new approach for affinity precipitation of mAbs and Fc fusion proteins under milder operating conditions using ZELP-E2 nanocages. The second component of the project will develop novel peptide affinity ligands for two classes of non-mAb proteins provided by our industrial collaborator BMS. The affinity peptides will then be employed in affinity precipitation formats to selectively capture the products from challenging feed stocks such as refolded protein pools and post-pegylation reaction mixtures. This work brings together Co-PIs with diverse expertise in protein engineering, peptide affinity design, affinity precipitation and downstream bioprocessing to develop entirely new classes of affinity precipitation reagents (Z-ELP-E2 nanocages, ELPaffinity peptides, and polyvalent affinity capture E2-(xAPy-ELP)) which if successful may result in a new integrated platform that will greatly simplify the recovery and purification of biological products. The proposed research could have a dramatic impact on the affinity capture of a broad range of therapeutic products represented by monoclonal antibodies, fusion proteins, biologics from inclusion bodies, and pegylated proteins. The combination of these novel technologies could represent entirely new approaches for the downstream processing of biologics with significant long-term industrial impact. Success in this work could not only impact the processing of difficult to recover and synthetically modified biologics but may also establish new paradigms for the bioprocessing of a wide range of many new biologics in development. This collaboration between academia and industry will serve as a proof-of-concept study for the potential industrial implementation of this transformative technology for the purification of biological products. Mechanisms for impact on education via graduate, undergraduate and K12 inclusion in research opportunities are discussed. This proposed molecular level and macroscopic separations level training is highly sought after by the biotechnology industry.
Karande,Pankaj / Chen,Wilfred 1403697 / 1403724伦斯勒理工学院/特拉华州大学拟议的项目是工业界(百时美施贵宝)和学术界(伦斯勒理工学院和特拉华州大学)之间的合作,旨在开发下一代和最先进的智能生物聚合物系统,用于工业生物加工中蛋白质治疗剂的纯化。在工业中存在对开发用于回收生物材料的新技术的显著需求和兴趣,与常规色谱方法相比,该技术在规模、成本和易于部署方面是有利的。PI建议开发亲和沉淀工艺,将亲和色谱的选择性沿着沉淀的可扩展性和成本效益相结合。该项目将采用新型亲和肽与有效的智能生物聚合物相结合,这些生物聚合物可以通过盐和/或温度的微小变化被诱导进出溶液。人们对开发用于生物制品的非色谱亲和回收方法非常感兴趣。亲和沉淀结合了亲和色谱的选择性沿着沉淀的可扩展性和成本效益。在NSF支持的先前研究中,PI已经使用与mAb结合Z结构域(ELP-Z)融合的弹性蛋白样多肽开发了一种可扩展的mAb亲和沉淀方法。拟议的工作建立在以前的工作,以产生全新类别的智能生物聚合物亲和试剂,并评估其实用性的工业纯化的单克隆抗体,FCfusions,和非单克隆抗体生物制剂的包涵体和聚乙二醇化过程。将与百时美施贵宝公司(BMS)合作,对它们的实际效用进行大规模蛋白质纯化评估。这项研究将为生物产品的大规模纯化提供一个灵活的平台。拟议项目的第一个组成部分将是一种新的方法,用于在温和的操作条件下使用ZELP-E2纳米笼亲和沉淀mAb和Fc融合蛋白。该项目的第二部分将为我们的工业合作者BMS提供的两类非mAb蛋白开发新型肽亲和配体。然后,亲和肽将以亲和沉淀形式使用,以选择性地捕获来自挑战性原料如重折叠蛋白质池和聚乙二醇化后反应混合物的产物。这项工作汇集了在蛋白质工程,肽亲和设计,亲和沉淀和下游生物加工方面具有不同专业知识的Co-PI,以开发全新类别的亲和沉淀试剂(Z-ELP-E2纳米笼,ELP亲和肽和多价亲和捕获E2-(xAPy-ELP)),如果成功,可能会产生一个新的集成平台,大大简化生物产品的回收和纯化。拟议的研究可能会对以单克隆抗体、融合蛋白、包涵体生物制剂和聚乙二醇化蛋白为代表的广泛治疗产品的亲和捕获产生巨大影响。这些新技术的结合可能代表生物制品下游加工的全新方法,具有重大的长期工业影响。这项工作的成功不仅可以影响难以回收和合成改性生物制剂的加工,而且还可以为开发中的许多新生物制剂的生物加工建立新的范例。学术界和工业界之间的这种合作将作为一种概念验证研究,用于这种用于生物产品纯化的变革性技术的潜在工业实施。讨论了通过研究生、本科生和K12纳入研究机会对教育产生影响的机制。这种提出的分子水平和宏观分离水平的培训受到生物技术行业的高度追捧。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Rapid Quantification of Monoclonal Antibody Titer in Cell Culture Harvests by Antibody-Induced Z-ELP-E2 Nanoparticle Cross-Linking
通过抗体诱导的 Z-ELP-E2 纳米颗粒交联快速定量细胞培养收获物中的单克隆抗体滴度
- DOI:10.1021/acs.analchem.8b04083
- 发表时间:2018
- 期刊:
- 影响因子:7.4
- 作者:Swartz, Andrew R.;Chen, Wilfred
- 通讯作者:Chen, Wilfred
High-efficiency affinity precipitation of multiple industrial mAbs and Fc-fusion proteins from cell culture harvests using Z-ELP-E2 nanocages: SWARTZ et al.
使用 Z-ELP-E2 纳米笼对细胞培养收获物中的多种工业 mAb 和 Fc 融合蛋白进行高效亲和沉淀:SWARTZ 等人。
- DOI:10.1002/bit.26717
- 发表时间:2018
- 期刊:
- 影响因子:3.8
- 作者:Swartz, Andrew R.;Xu, Xuankuo;Traylor, Steven J.;Li, Zheng Jian;Chen, Wilfred
- 通讯作者:Chen, Wilfred
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Wilfred Chen其他文献
Functional assembly and characterization of a modular xylanosome for hemicellulose hydrolysis in yeast
用于酵母半纤维素水解的模块化木糖体的功能组装和表征
- DOI:
10.1002/bit.24609 - 发表时间:
2013 - 期刊:
- 影响因子:3.8
- 作者:
S. Srikrishnan;Wilfred Chen;N. D. Da Silva - 通讯作者:
N. D. Da Silva
Engineering a high‐affinity scaffold for non‐chromatographic protein purification via intein‐mediated cleavage
通过内含肽介导的切割设计用于非层析蛋白质纯化的高亲和力支架
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:3.8
- 作者:
Fang Liu;Shen;Bhawna Madan;Wilfred Chen - 通讯作者:
Wilfred Chen
Peptide-Delivered Molecular Beacons Poliovirus-Infected Cells via TAT Quantitative Detection of Use of Flow Cytometry for Rapid
通过 TAT 快速定量检测流式细胞仪对脊髓灰质炎病毒感染细胞进行肽递送分子信标
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
M. Yates;Wilfred Chen;D. Sivaraman;Hsiao;A. Mulchandani - 通讯作者:
A. Mulchandani
High‐efficiency affinity precipitation of multiple industrial mAbs and Fc‐fusion proteins from cell culture harvests using Z‐ELP‐E2 nanocages
使用 Z-ELP-E2 纳米笼对细胞培养物中的多种工业 mAb 和 Fc 融合蛋白进行高效亲和沉淀
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:3.8
- 作者:
A. Swartz;Xuankuo Xu;Steven J Traylor;Z. Li;Wilfred Chen - 通讯作者:
Wilfred Chen
Customizable Biopolymers for Heavy Metal Remediation
用于重金属修复的可定制生物聚合物
- DOI:
10.1007/s11051-005-5132-y - 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
J. Kostal;G. Prabhukumar;U. L. Lao;Alin Chen;M. Matsumoto;A. Mulchandani;Wilfred Chen - 通讯作者:
Wilfred Chen
Wilfred Chen的其他文献
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{{ truncateString('Wilfred Chen', 18)}}的其他基金
Collaborative Research: NSF/MCB: Repurposing metabolite-responsive aptamers for real-time sensing and dynamic control of Cas6-mediated metabolon assembly
合作研究:NSF/MCB:重新利用代谢物响应适体,用于 Cas6 介导的代谢物组装的实时传感和动态控制
- 批准号:
2317398 - 财政年份:2023
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Logic-gated pro-MMP activation for tumor-specific motility in nanocarriers
纳米载体中肿瘤特异性运动的逻辑门控 MMP 前体激活
- 批准号:
2220667 - 财政年份:2023
- 资助金额:
$ 26.9万 - 项目类别:
Continuing Grant
Collaborative Research: Synthetic methane fixation cascades based on engineered membrane vesicles for biofuel cell applications
合作研究:基于工程膜囊泡的合成甲烷固定级联,用于生物燃料电池应用
- 批准号:
2221893 - 财政年份:2022
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Rapid purification of recombinant proteins by protein nanoparticle crosslinking and light-responsive nanobodies
通过蛋白质纳米颗粒交联和光响应纳米抗体快速纯化重组蛋白
- 批准号:
2040749 - 财政年份:2021
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Collaborative Research: Synthetic CRISPR-Cas6 endonucleases for dynamic control of cellular phenotypes in yeast
合作研究:用于动态控制酵母细胞表型的合成 CRISPR-Cas6 核酸内切酶
- 批准号:
2013991 - 财政年份:2020
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Collaborative Research: Dynamic degradation of proteins by ubiquitination provides a novel therapeutic for controlling elevated protein levels
合作研究:通过泛素化动态降解蛋白质为控制蛋白质水平升高提供了一种新的治疗方法
- 批准号:
1803008 - 财政年份:2018
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Collaborative Research: Redirecting cellular metabolism via synthetic toehold-gated dCas9 regulators
合作研究:通过合成的门控 dCas9 调节器重定向细胞代谢
- 批准号:
1817675 - 财政年份:2018
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Biochemical and Molecular Engineering XX Conference
生化与分子工程XX会议
- 批准号:
1739060 - 财政年份:2017
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
Repurposing the CRISPR-Cas9 system for dynamic control of cellular metabolism
重新利用 CRISPR-Cas9 系统动态控制细胞代谢
- 批准号:
1615731 - 财政年份:2016
- 资助金额:
$ 26.9万 - 项目类别:
Continuing Grant
Collaborative Research: Advanced biomanufacturing of functional bionanoparticles for biomedical engineering applications
合作研究:用于生物医学工程应用的功能性生物纳米颗粒的先进生物制造
- 批准号:
1604925 - 财政年份:2016
- 资助金额:
$ 26.9万 - 项目类别:
Standard Grant
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