Frontiers in Bioengineering and Biotechnology (Feb 2023)
A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice
- Chi-Yu Li,
- Chi-Yu Li,
- Chi-Yu Li,
- Chi-Yu Li,
- Ting Wu,
- Ting Wu,
- Ting Wu,
- Ting Wu,
- Xing-Jun Zhao,
- Xing-Jun Zhao,
- Xing-Jun Zhao,
- Xing-Jun Zhao,
- Cheng-Ping Yu,
- Cheng-Ping Yu,
- Cheng-Ping Yu,
- Cheng-Ping Yu,
- Zi-Xue Wang,
- Zi-Xue Wang,
- Zi-Xue Wang,
- Zi-Xue Wang,
- Xiao-Fang Zhou,
- Xiao-Fang Zhou,
- Xiao-Fang Zhou,
- Xiao-Fang Zhou,
- Shan-Ni Li,
- Shan-Ni Li,
- Shan-Ni Li,
- Shan-Ni Li,
- Jia-Da Li,
- Jia-Da Li,
- Jia-Da Li,
- Jia-Da Li
Affiliations
- Chi-Yu Li
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Chi-Yu Li
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Chi-Yu Li
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Chi-Yu Li
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Ting Wu
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Ting Wu
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Ting Wu
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Ting Wu
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Xing-Jun Zhao
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Xing-Jun Zhao
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Xing-Jun Zhao
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Xing-Jun Zhao
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Cheng-Ping Yu
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Cheng-Ping Yu
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Cheng-Ping Yu
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Cheng-Ping Yu
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Zi-Xue Wang
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Zi-Xue Wang
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Zi-Xue Wang
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Zi-Xue Wang
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Xiao-Fang Zhou
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Xiao-Fang Zhou
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Xiao-Fang Zhou
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Xiao-Fang Zhou
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Shan-Ni Li
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Shan-Ni Li
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Shan-Ni Li
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Shan-Ni Li
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- Jia-Da Li
- Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China
- Jia-Da Li
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China
- Jia-Da Li
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
- Jia-Da Li
- Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China
- DOI
- https://doi.org/10.3389/fbioe.2023.1052607
- Journal volume & issue
-
Vol. 11
Abstract
Exogenous insulin therapy is the mainstay treatment for Type-1 diabetes (T1D) caused by insulin deficiency. A fine-tuned insulin supply system is important to maintain the glucose homeostasis. In this study, we present a designed cell system that produces insulin under an AND gate control, which is triggered only in the presence of both high glucose and blue light illumination. The glucose-sensitive GIP promoter induces the expression of GI-Gal4 protein, which forms a complex with LOV-VP16 in the presence of blue light. The GI-Gal4:LOV-VP16 complex then promotes the expression of UAS-promoter-driven insulin. We transfected these components into HEK293T cells, and demonstrated the insulin was secreted under the AND gate control. Furthermore, we showed the capacity of the engineered cells to improve the blood glucose homeostasis through implantation subcutaneously into Type-1 diabetes mice.
Keywords
