Engineering smart cells for arthritis therapy

摘要 该项目的主要目标将是应用基因组编辑技术的最新发展来生成 一种高度先进的“智能”组织工程结构，以细胞为基础，反馈控制基因 表达作为一种自动调节的药物或生长因子传递的手段。这一系统的一个重要进步是 这些细胞将被编程为自动调节其活动，以响应环境信号。至 设计这个调控系统，干细胞(Ipscs)的基因调控电路将被重新布线以形成 由外部刺激激活的受控反馈环路，但随后会产生受控和自动调节的 回应。这些细胞将被用来形成组织工程结构，用于体外和体内测试。这个 该项目最初的重点将是创造包含人造基因电路的设计干细胞 提供抗炎药物输送，以应对环境。这些细胞将被工程改造成 稳定的软骨结构将被植入作为治疗自身免疫性疾病的方法 风湿性关节炎等疾病。创造“智能”细胞，提供自动化、长期、 反馈控制药物疗法代表了再生医学和关节炎的变革性范式 心理治疗。

Abstract The primary aim of this project will be to apply recent development of genome editing technologies to generate a highly advanced “smart” tissue-engineered construct featuring cell-based, feedback control of gene expression as a means of autoregulated drug or growth factor delivery. An important advance of this system is that cells will be programmed to automatically regulate their activity in response to environmental signals. To engineer this regulatory system, the gene regulation circuitry of stem cells (iPSCs) will be rewired to form controlled feedback loops that are activated by external stimuli, but then induce a controlled and autoregulated response. These cells will be used to form tissue-engineered constructs for in vitro and in vivo testing. The initial focus of the project will be on the creation of designer stem cells that contain artificial gene circuits that provide anti-inflammatory drug delivery in response to the environment. These cells will be engineered into stable cartilage constructs that will be implanted as a therapeutic approach for the treatment of autoimmune diseases such as rheumatoid arthritis. The creation of “smart” cells that provide automated, long-term, feedback-controlled drug therapy represents a transformative paradigm for regenerative medicine and arthritis therapy.