A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1052607/full |
| _version_ | 1811167270350618624 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Chi-Yu Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T16:06:30Z |
| format | Article |
| id | doaj.art-e662e5e7abab44f89d5189bbff77ed8f |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-10T16:06:30Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-e662e5e7abab44f89d5189bbff77ed8f2023-02-10T05:16:53ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-02-011110.3389/fbioe.2023.10526071052607A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in miceChi-Yu Li0Chi-Yu Li1Chi-Yu Li2Chi-Yu Li3Ting Wu4Ting Wu5Ting Wu6Ting Wu7Xing-Jun Zhao8Xing-Jun Zhao9Xing-Jun Zhao10Xing-Jun Zhao11Cheng-Ping Yu12Cheng-Ping Yu13Cheng-Ping Yu14Cheng-Ping Yu15Zi-Xue Wang16Zi-Xue Wang17Zi-Xue Wang18Zi-Xue Wang19Xiao-Fang Zhou20Xiao-Fang Zhou21Xiao-Fang Zhou22Xiao-Fang Zhou23Shan-Ni Li24Shan-Ni Li25Shan-Ni Li26Shan-Ni Li27Jia-Da Li28Jia-Da Li29Jia-Da Li30Jia-Da Li31Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaFurong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, ChinaHunan Key Laboratory of Medical Genetics, Central South University, Changsha, ChinaHunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, ChinaExogenous 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.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1052607/fulltype-1 diabetesoptogeneticchemigeneticAND gatecell-implanted therapy |
| spellingShingle | 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 A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice Frontiers in Bioengineering and Biotechnology type-1 diabetes optogenetic chemigenetic AND gate cell-implanted therapy |
| title | A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice |
| title_full | A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice |
| title_fullStr | A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice |
| title_full_unstemmed | A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice |
| title_short | A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice |
| title_sort | glucose blue light and gate controlled chemi optogenetic cell implanted therapy for treating type 1 diabetes in mice |
| topic | type-1 diabetes optogenetic chemigenetic AND gate cell-implanted therapy |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1052607/full |
| work_keys_str_mv | AT chiyuli aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali aglucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chiyuli glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT tingwu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xingjunzhao glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT chengpingyu glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT zixuewang glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT xiaofangzhou glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT shannili glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice AT jiadali glucosebluelightandgatecontrolledchemioptogeneticcellimplantedtherapyfortreatingtype1diabetesinmice |