Dual specificity antibodies using a double-stranded oligonucleotide bridge.
The covalent conjugation of oligonucleotides to antibody Fab' fragments was optimized by using oligonucleotides modified with a hexaethylene linker arm bearing three amino groups. One oligonucleotide was coupled to antibody of one specificity and a complementary oligonucleotide to antibody of a second specificity. The antibodies were then allowed to hybridize by base pairing of the complementary nucleotide sequences and the generation of bispecific antibody was analyzed on SDS-PAGE and confirmed using BIAcore analysis. The strategy of complementary oligonucleotide-linked bispecific molecules is not limited to antibodies but is applicable to linking any two molecules of different characteristics.
Chaudri
Z N
ZN
Department of Immunology, University College London, The Windeyer Institute for Medical Sciences, UK.
Bartlet-Jones
M
M
Panayotou
G
G
Klonisch
T
T
Roitt
I M
IM
Lund
T
T
Delves
P J
PJ
D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D015374:Biosensing Techniques; D004247:DNA / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D051379:Mice; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry*
D018033:Antibodies, Bispecific; D007140:Immunoglobulin Fab Fragments; D009841:Oligonucleotides; D004247:DNA