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.


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.


Targeted protein degradation

Supplementary materials

Supplementary information
Supporting figures, Material methods, Sequence information.


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