Microfluidic platform for gene delivery into the T-cells

用于将基因传递至 T 细胞的微流体平台

• 批准号: 10011520
• 负责人: Miguel CALERO-GARCIA
• 金额: $ 28.47万
• 依托单位: CELLFE INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011520
• 关键词: Ablation; Biological Assay; Blood Cells; CD19 gene; CD8-Positive T-Lymphocytes; CD8B1 gene; CRISPR/Cas technology; Cell Line; Cell Survival; Cell Volumes; Cells; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Convection; Coupled; DNA; DNA delivery; Data; Device Designs; Devices; Disease; Electroporation; Event; Formulation; Gene Delivery; Gene Expression Profile; Gene-Modified; Genes; Genetic; Genome; Goals; Gold; Grant; Height; Hematologic Neoplasms; Human; Ice; Immunologic Receptors; Interleukin-2; Investigation; Investments; Knock-in; Knock-out; Length; Life; Mechanics; Microfluidic Microchips; Microfluidics; Mission; Modification; Nonhomologous DNA End Joining; Nucleic Acids; Patients; Peripheral Blood Mononuclear Cell; Phase; Plasmids; Process; Protocols documentation; Reagent; Recovery; Reporter Genes; Reporting; Ribonucleoproteins; Route; Savings; Series; Side; T cell therapy; T-Cell Receptor; T-Lymphocyte; TNF gene; Technology; Testing; Therapeutic; Transfection; Transgenes; Viral Vector; allogeneic disease; cell type; chimeric antigen receptor T cells; cost; cost efficient; cytokine; cytotoxic; engineered T cells; gene therapy; genotoxicity; graft vs host disease; in vitro testing; plasmid DNA; prototype; repaired; scale up; success; therapeutic gene

Project Summary Ex vivo genetic m odif ication of blood cells has proven transf orm ational in the treatm ent of hem atologic disorders, most notably the hematologic malignancies using CAR-T or TCR-T cells. Despite considerable investment and some clinical success, gene-modified T cell therapy manufacturing remains costly and inefficient. New delivery technologies are needed to serve this growing market and facilitate access to T cell therapies. The mission of CellFE is to simplify manufacturing of life-saving ex vivo gene therapies using our unique, rapid and efficient capability to deliver gene modifying cargo to patient’s cells. The goal of this project is to test, optimize and scale up a proprietary technology that relies on microfluidic transfection by mechanical manipulation (“mechanotransfection”) to engineer T cells to express transgenes, and simultaneously knock out immune receptors such as T cell receptor (TCR). While the focus of this project is strictly on gene modification of T cells, our platform technology has the potential to impact all ex vivo gene therapy applications, including other blood cells amenable to CAR technology.

项目摘要 血细胞的离体遗传修饰已被证明在血液学病症的治疗中具有转基因作用， 最值得注意的是使用CAR-T或TCR-T细胞的血液恶性肿瘤。尽管投资巨大， 尽管取得了一些临床成功，但基因修饰的T细胞疗法制造仍然成本高昂且效率低下。新的交付 需要技术来服务于这个不断增长的市场，并促进获得T细胞疗法。的使命 CellFE将利用我们独特、快速和高效的技术， 将基因修饰货物递送到患者细胞的能力。 该项目的目标是测试，优化和扩大依赖于微流体的专有技术 通过机械操作转染（“机械转染”）以工程化T细胞以表达转基因，和 同时敲除免疫受体如T细胞受体（TCR）。虽然这个项目的重点是 严格地说，在T细胞的基因修饰上，我们的平台技术具有影响所有离体基因的潜力。 治疗应用，包括适用于CAR技术的其他血细胞。