title: Generation of a chickenized catalytic anti-nucleic acid antibody by complementarity-determining region grafting.
abstract: In contrast to a number of studies on the humanization of non-human antibodies, the reshaping of a non-human antibody into a chicken antibody has never been attempted. Therefore, nothing is known about the animal species-dependent compatibility of the framework regions (FRs) that sustain the appropriate conformation of the complementarity-determining regions (CDRs). In this study, we attempted the reshaping of the variable domains of the mouse catalytic anti-nucleic acid antibody 3D8 (m3D8) into the FRs of a chicken antibody (“chickenization”) by CDR grafting, which is a common method for the humanization of antibodies. CDRs of the acceptor chicken antibody that showed a high homology to the FRs of m3D8 were replaced with those of m3D8, resulting in the chickenized antibody (ck3D8). ck3D8 retained the biochemical properties (DNA binding, DNA hydrolysis, and cellular internalizing activities) and three-dimensional structure of m3D8 and showed reduced immunogenicity in chickens. Our study demonstrates that CDR grafting can be applied to the chickenization of a mouse antibody, probably due to the interspecies compatibility of the FRs.
authors.forename: Jooho
authors.initials: J
authors.lastname: Roh
authors.forename: Sung June
authors.initials: SJ
authors.lastname: Byun
authors.forename: Youngsil
authors.initials: Y
authors.lastname: Seo
authors.forename: Minjae
authors.initials: M
authors.lastname: KIm
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Songmi
authors.initials: S
authors.lastname: Kim
authors.forename: Yuno
authors.initials: Y
authors.lastname: Lee
authors.forename: Keun Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Jin-Kyoo
authors.initials: JK
authors.lastname: Kim
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D002384:Catalysis; D002645:Chickens; D022801:Complementarity Determining Regions / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009696:Nucleic Acids / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; C016512:IgY; D007136:Immunoglobulins; D009696:Nucleic Acids; D057127:Single-Chain Antibodies