Programmed aptamer target chain reaction (ATCR) for smart therapeutic inhibitor development
CHEMICAL ENGINEERING JOURNAL(2024)
摘要
Drug misdosing is a common cause of adverse effects. We first developed an aptamer target chain reaction (ATCR), which relies on a bivalent aptamer (HDTB-2) engineered with a sufficiently short spacer to continuously bind the target molecules, subsequently forming an aptamer target chain (ATC). ATCR is an universal, size-tunable, highly controllable, isothermal, self-assembly, and enzyme -free method for biomaterial formation. Through selecting aptamers with appropriate binding affinities, HDTB-2 inhibits target molecules only at the upregulated level and keeps it free at a healthy level to minimize the side effects due to misdosing. The design is applied as a smart anticoagulant, which exhibited stronger protection against misdosing and inhibition effects than commercial anticoagulants, due to the effective binding and enclosure of target molecules induced by the formation of bulky ATC. The efficacy and exceptional side effect management capability were further validated by a series of in vitro and in vivo experiments. To the best of our knowledge, this is the first report of a universal, non-covalently linked nucleic acidbiomolecule chain self-assembly method and a drug development technology that equips active pharmaceutical ingredients (API) with self-regulatory capability for smart management of the side effects.
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