期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 134, 期 51, 页码 20601-20604出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja310585e
关键词
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资金
- MIUR (FIRB Futuro in Ricerca)
- Bill & Melinda Gates Foundation through the Grand Challenges Explorations [OPP1061203]
- International Research Staff Exchange Scheme (IRSES) grant under the Marie Curie Actions program
- National Institutes of Health [R01EB007689]
- Fonds de Recherche du Quebec Nature et Technologies (FRQNT)
- Marie Curie Outgoing Fellowship (IOF) [298491]
- Bill and Melinda Gates Foundation [OPP1061203] Funding Source: Bill and Melinda Gates Foundation
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 concentration with greater precision than that achieved using mutational approaches. Using these methods, we generate sets of aptamers varying significantly in target affinity and then combine them to recreate several of the mechanisms employed by nature to narrow or broaden the dynamic range of biological receptors. Such ability to finely control the affinity and dynamic range of aptamers may find many applications in synthetic biology, drug delivery, and targeted therapies, fields in which aptamers are of rapidly growing importance.
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