Apt-clean: Aptamer-mediated cleavage of extracellular antigen, a new strategy for the inhibition of membrane protein functions

13 October 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Recently, targeted protein degradation (TPD) has attracted much attention as a powerful strategy for effective inhibition of disease-related proteins. However, development of ligands with high affinity and specificity for a target protein is still a demanding task and poses a particular challenge for designing TPD therapeutics. In this work, we report a novel TPD strategy called aptamer-mediated cleavage of extracellular antigen (Apt-clean), where oligonucleotide-based affinity agents are used for selective recruitment of proteases to target membrane proteins. Our data demonstrate that Apt-clean induces selective degradation of the target protein both in vitro and in cellulo. In addition, potential of Apt-clean was demonstrated through the inhibition of a tumor-related growth factor signaling. This novel TPD modality may serve as an efficient and flexible strategy for targeting membrane proteins.

Keywords

Aptamers
Targeted protein degradation

Supplementary materials

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Supplementary information
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Supporting figures, Material methods, Sequence information.
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