In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 11, No. 515 ( 2019-10-23)
Abstract:
Cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. Here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (PCA), a metabolite found in green tea. We constructed multiple genetic control technologies that could toggle a PCA-responsive ON/OFF switch based on a transcriptional repressor from Streptomyces coelicolor . We demonstrated that PCA-controlled switches can be used for guide RNA expression–mediated control of the CRISPR-Cas9 systems for gene editing and epigenetic remodeling. We showed how these technologies could be used as implantable biocomputers in live mice to perform complex logic computations that integrated signals from multiple food metabolites. Last, we used our system to treat type 1 and type 2 diabetes in mice and cynomolgus monkeys. This biocompatible and versatile food phenolic acid–controlled transgenic device opens opportunities for dynamic interventions in gene- and cell-based precision medicine.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aav8826
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2019
