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A glucose-blue light AND gate-controlled chemi-optogenetic cell-implanted therapy for treating type-1 diabetes in mice.
Li, Chi-Yu; Wu, Ting; Zhao, Xing-Jun; Yu, Cheng-Ping; Wang, Zi-Xue; Zhou, Xiao-Fang; Li, Shan-Ni; Li, Jia-Da.
Afiliação
  • Li CY; Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
  • Wu T; Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China.
  • Zhao XJ; Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China.
  • Yu CP; Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China.
  • Wang ZX; Furong Laboratory, Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
  • Zhou XF; Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China.
  • Li SN; Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China.
  • Li JD; Hunan International Scientific and Technological Cooperation Base of Animal Models for Human Disease, Changsha, China.
Front Bioeng Biotechnol ; 11: 1052607, 2023.
Article em En | MEDLINE | ID: mdl-36845170
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article