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

Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells. Love, Kasey S. et al., Cell Systems, Volume 0, Issue 0, 101269 DOI: 10.1016/j.cels.2025.101269

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 developed a single-transcript, microRNA-based incoherent feedforward loop called compact microRNA-mediated attenuator of noise and dosage (ComMAND).

ComMAND effectively sets levels of the clinically relevant transgenes frataxin (FXN) and fragile X messenger ribonucleoprotein 1 (Fmr1) within a narrow window.

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