Synthetic closed-loop gene circuit for phenylalanine regulation.

ABSTRACT: Genetic programming of cells offers significant potential for developing next-generation cell-based therapies that detect and respond to signals within the patient's body to treat chronic diseases. Closed-loop systems designed to self-regulate in response to abnormal biomarker levels are particularly attractive for biomedical applications. In this study, we engineered PRO (phenylalanine regulation orchestration), a cell-autonomous genetic system capable of sensing and degrading elevated levels of phenylalanine, an essential amino acid that accumulates to pathological levels in patients with phenylketonuria (PKU). Central to this system is a transcriptional switch relying on the regulatory domain of human phenylalanine hydroxylase, which dimerizes in the presence of phenylalanine to reconst

SUBMITTER: Galvan S 

PROVIDER: S-EPMC12585910 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature