An Internalizing Antibody Specific for the Human Asialoglycoprotein Receptor

The liver possesses a variety of characteristics that make this organ a very attractive target for gene and drug delivery. The asialoglycoprotein receptor (ASGPR) is a heterodimeric liver-specific C-type lectin that mediates endocytosis and degradation of desialylated glycoproteins and is considered a preferable target for liver-specific drug delivery. Asialoglycoprotein-coupled, galactosylated, or anti-ASGPR antibody-targeted molecules may be used to deliver pharmaceutical agents to the liver. Here we present a new anti-ASGPR single-chain antibody (scFv) that was isolated from the synthetic human "Ronit-1" antibody phage display library. This scFv (B11) was shown to bind the recombinant and native forms of the ASGPR and could also facilitate ASGPR specific internalization of a B11-PE38KDEL immunotoxin and cause cell death. Thus, this newly isolated antibody can serve as a targeting moiety for ASGPR-directed drug delivery.