Adaptable and scalable electroporation for cellular therapy
用于细胞治疗的适应性和可扩展的电穿孔
基本信息
- 批准号:10545845
- 负责人:
- 金额:$ 27.52万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptive Cell TransfersBenchmarkingBudgetsCRISPR/Cas technologyCell SurvivalCell TherapyCell physiologyCellsCellular biologyClinicalComplexDNADNA deliveryDevicesDiseaseElectroporationEnsureEnvironmentGenerationsGenesGeometryGreen Fluorescent ProteinsHumanInheritedJurkat CellsKnock-outLiquid substanceMessenger RNAMethodsModificationNucleic AcidsPerformancePhaseProcessProductionProteinsRNAReproducibilityResearchRibonucleoproteinsSamplingSystemT-LymphocyteTechnologyTherapeuticThinnessTransfectionTransposaseVaccinationValidationVariantViralViral Vectorchimeric antigen receptorchimeric antigen receptor T cellsclinically relevantclinically significantcost effectivedesigndrug discoveryelectric fieldexperiencefluid flowknock-downmRNA ExpressionmRNA deliverynovelplasmid DNAprogrammed cell death protein 1prototypereceptorstem cell therapytherapy developmenttransgene expressiontransposon/insertion elementtrend
项目摘要
Project Summary
Cellular therapies have demonstrated the potential to treat a variety of inherited and acquired
diseases, but the first generation of approved cell therapies rely on viral vectors for cellular
reprogramming. Viral vectors are recognized as a bottleneck in the development of these
therapies and other delivery methods, like electroporation, are being clinically investigated. To
address limitations in existing electroporation technology, CyteQuest is developing a simple,
scalable electroporation platform to optimize transfection parameters and deliver cargo
efficiently and reproducibly at high throughput. CyteQuest’s platform consists of a planar flow
chip with a thin slab geometry that ensures that cells are subject to a uniform electrical field for
reproducible electroporation. The flow cell geometry allows for seamless scaling to a high-
volume system for delivery at clinical scale. The key objectives of this proposal are to: (1)
demonstrate high-efficiency delivery of clinically relevant cargo including CRISPR/Cas9
ribonucleoprotein complexes to primary human T cells, and (2) construct a prototype large-
volume electroporation flow system compatible with the volumetric throughput required for
cellular therapy in a clinical setting. CyteQuest will demonstrate that the optimized
electroporation parameters of the small volume system can be used directly in the high-volume
system with less than 5% variation in the biomolecular delivery efficiency and cell viability. The
high-volume electroporation flow system can be manufactured in a process that is cost-effective
and robust. CyteQuest ultimately aims to use this novel platform in conjunction with
CRISPR/Cas9 technology as a therapeutic application for adoptive cell therapy.
项目摘要
细胞疗法已经证明了治疗各种遗传性和获得性疾病的潜力。
疾病,但第一代被批准的细胞疗法依赖于病毒载体的细胞
重新编程。病毒载体被认为是这些疾病发展的瓶颈。
治疗方法和其他给药方法,如电穿孔,正在进行临床研究。至
针对现有电穿孔技术的局限性,CyteQuest正在开发一种简单、
可扩展的电穿孔平台,用于优化转染参数和运送货物
在高吞吐量下高效且可重现。CyteQuest的平台由平面流组成
具有薄板几何结构的芯片,确保电池受到均匀电场的影响
可重复的电穿孔。流动单元的几何形状允许无缝缩放到一个高-
用于临床规模交付的体积系统。这项建议的主要目标是:(1)
展示临床相关货物的高效交付,包括CRISPR/CAS9
核糖核蛋白与原代人类T细胞的结合,以及(2)构建了一个大分子核糖核蛋白复合体。
体积电穿孔流动系统与所需的体积吞吐量相兼容
临床环境中的细胞治疗。CyteQuest将展示经过优化的
小体积系统的电穿孔参数可以直接用于大体积
生物分子递送效率和细胞活力的变化小于5%的系统。这个
可以以成本效益高的工艺制造大容量电穿孔流动系统
而且很健壮。CyteQuest最终的目标是将这一新颖的平台与
CRISPR/Cas9技术在过继细胞治疗中的应用
项目成果
期刊论文数量(2)
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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HAROLD G CRAIGHEAD其他文献
HAROLD G CRAIGHEAD的其他文献
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{{ truncateString('HAROLD G CRAIGHEAD', 18)}}的其他基金
Tools for Single Molecule and Single Cell Epigenomic Analysis
单分子和单细胞表观基因组分析工具
- 批准号:
8340779 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
Tools for Single Molecule and Single Cell Epigenomic Analysis
单分子和单细胞表观基因组分析工具
- 批准号:
8683212 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
Tools for Single Molecule and Single Cell Epigenomic Analysis
单分子和单细胞表观基因组分析工具
- 批准号:
8534233 - 财政年份:2012
- 资助金额:
$ 27.52万 - 项目类别:
In vivo Detection and Imaging of Epigenetic Histone Modifications and Modifying E
表观遗传组蛋白修饰和修饰 E 的体内检测和成像
- 批准号:
8269067 - 财政年份:2010
- 资助金额:
$ 27.52万 - 项目类别:
In vivo Detection and Imaging of Epigenetic Histone Modifications and Modifying E
表观遗传组蛋白修饰和修饰 E 的体内检测和成像
- 批准号:
8144800 - 财政年份:2010
- 资助金额:
$ 27.52万 - 项目类别:
In vivo Detection and Imaging of Epigenetic Histone Modifications and Modifying E
表观遗传组蛋白修饰和修饰 E 的体内检测和成像
- 批准号:
8471090 - 财政年份:2010
- 资助金额:
$ 27.52万 - 项目类别: