Mahameed Mohamed, Fussenegger Martin
ETH Zurich, Department of Biosystems Science and Engineering, Mattenstrasse 26, CH-4058 Basel, Switzerland.
University of Basel, Faculty of Life Science, 4001 Basel, Switzerland.
iScience. 2022 Jan 29;25(3):103834. doi: 10.1016/j.isci.2022.103834. eCollection 2022 Mar 18.
Synthetic biology has made it possible to engineer mammalian cells for on-demand delivery of therapeutic agents, providing therapeutic solutions for chronic or intractable diseases. Currently, most of the engineered therapeutic cells are regulated by the administration of exogenous inducers, but the need for repeated administration of these xenobiotics is problematic from the viewpoints of patients' compliance and quality of life, as well as possible side effects. Recently, synthetic biologists started to address these issues by constructing autonomous, closed-loop therapeutic cells, often referred to as designer cells. These cells are equipped with sensing modules that detect and link marker(s) of the target disease to signaling cascades that stimulate the secretion of specified therapeutic agents in a timely and quantitative manner, without the need of exogenous inducers. Here, we review recent work on designer cell engineering and their therapeutic applications, focusing on the molecular mechanisms and signaling pathways employed.
合成生物学使得对哺乳动物细胞进行工程改造以按需递送治疗剂成为可能，为慢性或难治性疾病提供了治疗方案。目前，大多数工程化治疗细胞受外源性诱导剂给药的调控，但从患者依从性和生活质量以及可能的副作用来看，重复给药这些异生物质存在问题。最近，合成生物学家开始通过构建自主的闭环治疗细胞（通常称为设计细胞）来解决这些问题。这些细胞配备了传感模块，可检测目标疾病的标志物并将其与信号级联反应相联系，从而及时、定量地刺激特定治疗剂的分泌，而无需外源性诱导剂。在此，我们综述了设计细胞工程及其治疗应用的近期研究工作，重点关注所采用的分子机制和信号通路。
