{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(12)"],"submitter":["Ma Y"],"pubmed_abstract":["Despite significant progress in extracellular targeted protein degradation (eTPD), existing approaches rarely achieved tissue-specific drug accumulation while maintaining efficient systemic clearance, a critical challenge in treating bone disorders. In this study, we introduced GalNAc-Apc001, a novel aptamer-based lysosome-targeting chimera (LYTAC) that uniquely combined bone-specific retention with hepatocyte-mediated clearance through a spatiotemporally controlled mechanism. By conjugating a tri-N-acetylgalactosamine (GalNAc) moiety to a bone-homing sclerostin aptamer (Apc001), we engineered a bifunctional molecule capable of accumulating in bone via hydroxyapatite binding, capturing circulating sclerostin with high affinity and directing it to hepatocytes for ASGPR-mediated lysosomal de"],"journal":["JACS Au"],"pagination":["5973-5984"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12728634"],"repository":["biostudies-literature"],"pubmed_title":["Harnessing Bone-Liver Crosstalk: A Dual-Action LYTAC Approach for Bone-Specific Accumulation and Liver-Specific Protein Degradation in Bone Disorders."],"pmcid":["PMC12728634"],"pubmed_authors":["Zhang G","Pan Y","Yu S","Zhong C","Jiang H","Zhang H","Ma Y","Luo H","Lu A","Wang L","Yang X","Chen Z","Zhang Y","Amu G","Tao X","Zhang B","Yu Y"],"additional_accession":[]},"is_claimable":false,"name":"Harnessing Bone-Liver Crosstalk: A Dual-Action LYTAC Approach for Bone-Specific Accumulation and Liver-Specific Protein Degradation in Bone Disorders.","description":"Despite significant progress in extracellular targeted protein degradation (eTPD), existing approaches rarely achieved tissue-specific drug accumulation while maintaining efficient systemic clearance, a critical challenge in treating bone disorders. In this study, we introduced GalNAc-Apc001, a novel aptamer-based lysosome-targeting chimera (LYTAC) that uniquely combined bone-specific retention with hepatocyte-mediated clearance through a spatiotemporally controlled mechanism. By conjugating a tri-N-acetylgalactosamine (GalNAc) moiety to a bone-homing sclerostin aptamer (Apc001), we engineered a bifunctional molecule capable of accumulating in bone via hydroxyapatite binding, capturing circulating sclerostin with high affinity and directing it to hepatocytes for ASGPR-mediated lysosomal de","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-06T05:45:20.293Z","creation":"2026-05-26T03:12:29.959Z"},"accession":"S-EPMC12728634","cross_references":{"pubmed":["41450662"],"doi":["10.1021/jacsau.5c00827"]}}