Apt-clean: aptamer-mediated cleavage of extracellular antigens for the inhibition of membrane protein functions. (3rd January 2023)

• Record Type: Journal Article
• Authors: Hoshiyama, Junya; Okada, Yuga; Cho, Seojung; Ueki, Ryosuke; Sando, Shinsuke
• Is Part Of: Biomaterials science. Volume 11:Number 2(2023)
• Page Start: 445
• Page End: 449
• Publication Date: 2023-01-03
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d2bm01695h
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A novel TPD strategy called aptamer-mediated cleavage of extracellular antigen (Apt-clean) induces selective degradation of the target membrane protein. 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, the potential of Apt-clean was demonstrated through the inhibition of tumor-related growth factor signaling. This novel TPD modality may serve as an efficient and flexible strategy for targeting membrane proteins.