Institute of Biomaterials and Biomedical Engineering , University of Toronto , 164 College Street , Toronto , Ontario M5S 3G9 , Canada.
Edward S. Rogers, Sr. Department of Electrical and Computer Engineering , University of Toronto , 10 King's College Circle , Toronto , Ontario M5S 3G4 , Canada.
Biochemistry. 2019 Mar 19;58(11):1484-1491. doi: 10.1021/acs.biochem.8b01081. Epub 2018 Dec 5.
Breakthroughs in gene synthesis has allowed synthetic biologists the ability to design any DNA sequence of interest, enabling the possibility to create complex systems inside cells with novel functions to tackle problems in immunology. Synthetic immunology of mammalian cells expressing natural or synthetic genes can guide and induce immune responses in patients. Through recent developments in engineering chimeric receptors, it is now feasible to customize control over engineered cells to target the disease sites with specificity. These cells can avoid immune rejection if derived from expandable cell types (e.g., stem cells or T cells) and then can be grown in abundance before implantation. However, safety concerns of engineered cells in circulation necessitates the development of a wide range of mechanisms to kill cells after their therapeutic life ends. This therapeutic effect is still predominantly the secretion of therapeutic proteins, but novel therapeutic interventions have been explored by synthetic biologists. In the pursuit of engineering new cell functions for synthetic immunology, it is possible that many problems previously thought intractable may actually be possible.
基因合成的突破使合成生物学家能够设计任何感兴趣的 DNA 序列,从而有可能在细胞内创建具有新功能的复杂系统,以解决免疫学中的问题。表达天然或合成基因的哺乳动物细胞的合成免疫学可以指导和诱导患者的免疫反应。通过嵌合受体工程的最新进展,现在可以定制对工程细胞的控制,以特异性靶向疾病部位。如果这些细胞来自可扩增的细胞类型(例如干细胞或 T 细胞),则可以在植入前大量生长,从而避免免疫排斥。然而,循环中的工程细胞的安全性问题需要开发广泛的机制来在其治疗寿命结束后杀死细胞。这种治疗效果主要仍然是治疗性蛋白质的分泌,但合成生物学家已经探索了新的治疗干预措施。在为合成免疫学设计新的细胞功能时,以前认为难以解决的许多问题实际上可能是可行的。