Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.

ABSTRACT: To realize the potential of engineered cells in therapeutic applications, transgenes must be expressed within the window of therapeutic efficacy. Differences in copy number and other sources of extrinsic noise generate variance in transgene expression and limit the performance of synthetic gene circuits. In a therapeutic context, supraphysiological expression of transgenes can compromise engineered phenotypes and lead to toxicity. To ensure a narrow range of transgene expression, we design and characterize Compact microRNA-Mediated Attenuator of Noise and Dosage (ComMAND), a single-transcript, microRNA-based incoherent feedforward loop. We experimentally tune the ComMAND output profile, and we model the system to explore additional tuning st

SUBMITTER: Love KS 

PROVIDER: S-EPMC11230401 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature