Ribosome display for improved biotherapeutic molecules.
Ribosome display presents an innovative in vitro technology for the rapid isolation and evolution of high-affinity peptides or proteins. Displayed proteins are bound to and recovered from target molecules in multiple rounds of selection in order to enrich for specific binding proteins. No transformation step is necessary, which could lead to a loss of library diversity. A cycle of display and selection can be performed in one day, enabling the existing gene repertoire to be rapidly scanned. Proteins isolated from the panning rounds can be further modified through random or directed molecular evolution for affinity maturation, as well as selected for characteristics such as protein stability, folding and functional activity. Recently, the field of display technologies has become more prominent due to the generation of new scaffolds for ribosome display, isolation of high-affinity human antibodies by phage display, and their implementation in the discovery of novel protein-protein interactions. Applications for this technology extend into the broad field of antibody engineering, proteomics, and synthetic enzymes for diagnostics and therapeutics in cancer, autoimmune and infectious diseases, neurodegenerative diseases and inflammatory disorders. This review highlights the role of ribosome display in drug discovery, discusses advantages and disadvantages of the system, and attempts to predict the future impact of ribosome display technology on the development of novel engineered biopharmaceutical products for biological therapies.
Rothe
Achim
A
CSIRO Molecular and Health Technologies, 343 Royal Parade, Parkville, Victoria 3052, Australia.
Hosse
Ralf J
RJ
Power
Barbara E
BE
D000818:Animals; D000906:Antibodies; D001691:Biological Therapy / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019143:Evolution, Molecular; D015723:Gene Library; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000473:pathology; D019151:Peptide Library; D011485:Protein Binding; D014176:Protein Biosynthesis; D017510:Protein Folding; D012269:Ribosomal Proteins / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
D000906:Antibodies; D018076:DNA, Complementary; D019151:Peptide Library; D012269:Ribosomal Proteins