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.
Trahtenherts
Alla
A
Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Israel.
Benhar
Itai
I
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry; D037263:Asialoglycoprotein Receptor / Q000737:chemistry* / Q000276:immunology*; D001212:Asialoglycoproteins / Q000737:chemistry; D001483:Base Sequence; D016923:Cell Death; D002470:Cell Survival; D016503:Drug Delivery Systems; D004705:Endocytosis; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry; D008099:Liver / Q000276:immunology; D008969:Molecular Sequence Data; D019151:Peptide Library; D011994:Recombinant Proteins / Q000737:chemistry
D000906:Antibodies; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D037181:Lectins, C-Type; D019151:Peptide Library; D011994:Recombinant Proteins