Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting.
Humanization of nonhuman antibodies (Abs) has been carried out mainly for Abs which bind to antigen without catalytic activity. Here we report humanization of mouse-originated 3D8 (m3D8) mAbs (scFv, VH, and VL) with DNA hydrolyzing catalytic activity by grafting the complementarity determining regions (CDRs) into the corresponding regions of a fixed human framework scaffold, generating humanized 3D8 (h3D8) Abs in the respective format of scFv, VH, and VL. h3D8 Abs retained comparable DNA binding and hydrolyzing activities to those of the corresponding m3D8 Abs. Our results suggest that CDRs of anti-DNA hydrolyzing Abs might possess the intrinsic properties of DNA binding and hydrolyzing activities.
Kim
Dong-Sik
DS
Department of Molecular Science and Technology, Ajou University, San 5, Woncheon-dong, Yeongtong-gu, Suwon 443-749, Republic of Korea.
Lee
Seung-Hyun
SH
Kim
Jeong-Sun
JS
Lee
Suk-Chan
SC
Kwon
Myung-Hee
MH
Kim
Yong-Sung
YS
D000595:Amino Acid Sequence; D000818:Animals; D017151:Antibodies, Catalytic / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D022801:Complementarity Determining Regions / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D004247:DNA / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D004247:DNA