去唾液酸糖蛋白受体
化学
效力
寡核苷酸
凝集素
结合
生物化学
配体(生物化学)
受体
分子生物学
立体化学
肝细胞
体外
基因
生物
数学分析
数学
作者
Garth A. Kinberger,Thazha P. Prakash,Jinghua Yu,Guillermo Vasquez,Audrey Low,Alfred E. Chappell,Karsten Schmidt,Heather Murray,Hans Gaus,Eric E. Swayze,Punit P. Seth
标识
DOI:10.1016/j.bmcl.2016.05.084
摘要
Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10-fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)—a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5–10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency.
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