Applications of ribosome display to antibody drug discovery.
Ribosome display is a polymerase chain reaction-based in vitro display technology that is well suited to the selection and evolution of high affinity antibodies. Both eukaryotic and prokaryotic translation systems have been applied to ribosome display, and the technology's utility has been demonstrated in the antibody isolation process. In particular, ribosome display lends itself to the evolution of functional characteristics, such as potency, of lead candidate antibodies to provide therapeutic antibodies. Large libraries (10(12)) can be rapidly constructed, antibodies selected, and sequence space extensively explored by targeted mutagenesis techniques or by random mutagenesis throughout the antibody sequence. Using such approaches in ribosome display systems lead antibodies derived from phage display or from immunised animals have been improved > 1000-fold in potency within 6 months. This review will discuss the technology and give an insight into how ribosome display is being applied to the antibody lead discovery and optimisation processes.
Groves
Maria A T
MA
Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge, CB16GH, UK.
Osbourn
Jane K
JK
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000235:genetics*; D015723:Gene Library; D006801:Humans; D012270:Ribosomes / Q000235:genetics*; D013678:Technology, Pharmaceutical / Q000379:methods*
D000906:Antibodies