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Genetic-code-expanded Cell-based Therapy for Treating Diabetes in Mice by Chao Chen; Guiling Yu; Yujia Huang; Wenhui Cheng; Yuxuan Li; Yi Sun; Haifeng Ye; Tao Liu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Genetic-code-expanded Cell-based Therapy for Treating Diabetes in Mice about?

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.

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Author

Chao Chen; Guiling Yu; Yujia Huang; Wenhui Cheng; Yuxuan Li; Yi Sun; Haifeng Ye; Tao Liu

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)