Speaker
Description
Gene regulation is a complex web across biological levels, and its intricacy often complicates pre- cise interventions, with off-target effects being a major hurdle. To transform this, we here propose a photoactivatable microRNA-based circuit that enables unmatched accuracy in gene targeting, po- tentially reducing off-target effects. Our approach leverages the concept of microRNAs (miRNAs) as frequency decoders, interpreting signal frequencies—such as oscillatory pulses—to regulate vi- tal cellular processes. We’ve recently shown that periodically expressed miRNAs can selectively repress targets within specific frequency ranges, creating bell-shaped response curves typical of true frequency decoders. Our model highlights the importance of miRNA-target interaction dy- namics in frequency-dependent repression, adding an orthogonal layer of specificity beyond mere sequence pairing. After introducing our theoretical results, we present a simple yet powerful cir- cuit in which a photoactivatable miRNA, whose expression can be periodically controlled by light, enables dynamic gene expression modulation in single cells.
