Here we demonstrate multiple, complementary approaches by which to tune, extend, or
narrow the dynamic range of aptamer-based sensors. Specifically, we employ both distal-
site mutations and allosteric control to tune the affinity and dynamic range of a fluorescent
aptamer beacon. We show that allosteric control, achieved by using a set of easily designed
oligonucleotide inhibitors that competes against the folding of the aptamer, allows rational
fine-tuning of the affinity of our model aptamer across 3 orders of magnitude of target …