诱导剂
生物
转录因子
细胞
计算生物学
细胞生物学
癌症研究
遗传学
基因
作者
Chao Chen,Guiling Yu,Yujia Huang,Wenhui Cheng,Yuxuan Li,Yi Sun,Haifeng Ye,Tao Liu
标识
DOI:10.1038/s41589-021-00899-z
摘要
Inducer-triggered therapeutic protein expression from designer cells is a promising strategy for disease treatment. However, as most inducer systems harness transcriptional machineries, protein expression timeframes are unsuitable for many therapeutic applications. Here, we engineered a genetic code expansion-based therapeutic system, termed noncanonical amino acids (ncAAs)-triggered therapeutic switch (NATS), to achieve fast therapeutic protein expression in response to cognate ncAAs at the translational level. The NATS system showed response within 2 hours of triggering, whereas no signal was detected in a transcription-machinery-based system. Moreover, NATS system is compatible with transcriptional switches for multi-regulatory-layer control. Diabetic mice with microencapsulated cell implants harboring the NATS system could alleviate hyperglycemia within 90 min on oral delivery of ncAA. We also prepared ncAA-containing ‘cookies’ and achieved long-term glycemic control in diabetic mice implanted with NATS cells. Our proof-of-concept study demonstrates the use of NATS system for the design of next-generation cell-based therapies to achieve fast orally induced protein expression. The development of a genetic code expansion-based system enables fast protein expression in response to a noncanonical amino acid. The system was implanted into diabetic mice to rescue hyperglycemia with oral delivery of the amino acid.
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