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Engineering living therapeutics with synthetic biology
Nature Reviews Drug Discovery ( IF 122.7 ) Pub Date : 2021-10-06 , DOI: 10.1038/s41573-021-00285-3
Andres Cubillos-Ruiz 1, 2 , Tingxi Guo 3, 4 , Anna Sokolovska 5 , Paul F Miller 6 , James J Collins 1, 2 , Timothy K Lu 3, 4 , Jose M Lora 7
Affiliation  

The steadfast advance of the synthetic biology field has enabled scientists to use genetically engineered cells, instead of small molecules or biologics, as the basis for the development of novel therapeutics. Cells endowed with synthetic gene circuits can control the localization, timing and dosage of therapeutic activities in response to specific disease biomarkers and thus represent a powerful new weapon in the fight against disease. Here, we conceptualize how synthetic biology approaches can be applied to programme living cells with therapeutic functions and discuss the advantages that they offer over conventional therapies in terms of flexibility, specificity and predictability, as well as challenges for their development. We present notable advances in the creation of engineered cells that harbour synthetic gene circuits capable of biological sensing and computation of signals derived from intracellular or extracellular biomarkers. We categorize and describe these developments based on the cell scaffold (human or microbial) and the site at which the engineered cell exerts its therapeutic function within its human host. The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine that holds great promise for the development of effective treatments for a wide variety of human diseases.



中文翻译:

用合成生物学设计活体疗法

合成生物学领域的稳步发展使科学家能够使用基因工程细胞,而不是小分子或生物制剂,作为开发新疗法的基础。具有合成基因回路的细胞可以控制针对特定疾病生物标志物的治疗活动的定位、时间和剂量,从而成为对抗疾病的强大新武器。在这里,我们概念化了如何将合成生物学方法应用于对具有治疗功能的活细胞进行编程,并讨论它们在灵活性、特异性和可预测性方面相对于传统疗法的优势,以及它们的发展面临的挑战。我们展示了在创建具有合成基因电路的工程细胞方面的显着进展,这些合成基因电路能够生物传感和计算源自细胞内或细胞外生物标志物的信号。我们根据细胞支架(人类或微生物)和工程细胞在其人类宿主内发挥其治疗功能的位点对这些发展进行分类和描述。使用合成生物学设计基于细胞的疗法是医学中一种快速发展的策略,它为开发各种人类疾病的有效疗法带来了巨大希望。我们根据细胞支架(人类或微生物)和工程细胞在其人类宿主内发挥其治疗功能的位点对这些发展进行分类和描述。使用合成生物学设计基于细胞的疗法是医学中一种快速发展的策略,它为开发各种人类疾病的有效疗法带来了巨大希望。我们根据细胞支架(人类或微生物)和工程细胞在其人类宿主内发挥其治疗功能的位点对这些发展进行分类和描述。使用合成生物学设计基于细胞的疗法是医学中一种快速发展的策略,它为开发各种人类疾病的有效疗法带来了巨大希望。

更新日期:2021-10-06
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