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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 FROM AUTHOR]

In their Communication (e202218106), Zhi Zhu et al. report the development of aptamer-LYTACs (lysosome targeting chimeras) for the efficient degradation of the platelet-derived growth factor and the membrane protein PTK7 through the lysosomal degradation pathway. Aptamers, Extracellular Proteins, LYTACs, Membrane Proteins, Targeted Degradation Keywords: Aptamers; Extracellular Proteins; LYTACs; Membrane Proteins; Targeted Degradation EN Aptamers Extracellular Proteins LYTACs Membrane Proteins Targeted Degradation 1 1 1 03/29/23 20230403 NES 230403 B Aptamers b . [Extracted from the article]