Aptamer‐LYTACs for Targeted Degradation of Extracellular and Membrane Proteins. (20th February 2023)

• Record Type: Journal Article
• Authors: Wu, Yuqi; Lin, Bingqian; Lu, Yinzhu; Li, Liang; Deng, Kunyue; Zhang, Suhui; Zhang, Huiming; Yang, Chaoyong; Zhu, Zhi
• Is Part Of: Angewandte Chemie. Volume 135:Number 15(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-20
• Subjects: Aptamers -- Extracellular Proteins -- LYTACs -- Membrane Proteins -- Targeted Degradation; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202218106
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Recently, lysosome targeting chimeras (LYTACs) have emerged as a promising technology that expands the scope of targeted protein degradation to extracellular targets. However, the preparation of chimeras by conjugation of the antibody and trivalent N‐acetylgalactosamine (tri‐GalNAc) is a complex and time‐consuming process. The large uncertainty in number and position and the large molecular weights of the chimeras result in low internalization efficiency. To circumvent these problems, we developed the first aptamer‐based LYTAC (Apt‐LYTAC) to realize liver‐cell‐specific degradation of extracellular and membrane proteins by conjugating aptamers to tri‐GalNAc. Taking advantage of the facile synthesis and low molecular weight of the aptamer, the Apt‐LYTACs can efficiently and quickly degrade the extracellular protein PDGF and the membrane protein PTK7 through a lysosomal degradation pathway. We anticipate that the novel Apt‐LYTACs will expand the usage of aptamers and provide a new dimension for targeted protein degradation. Abstract : Aptamer‐LYTACs have been developed by conjugating aptamers to tri‐GalNAc to realize liver‐cell‐specific degradation of extracellular and membrane proteins. This platform can efficiently and quickly degrade the extracellular protein PDGF and the membrane protein PTK7 through the lysosomal degradation pathway, providing a new method for targeted protein degradation.