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.
Aptamers. 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.