In 1997, Roberts and Szostak showed that fusions between a synthetic mRNA and its encoded myc epitope could be enriched from a pool of random sequence mRNA-polypeptide fusions by immunoprecipitation.
Nine years later, Fukuda and colleagues chose mRNA display method for in vitro evolution of single-chain Fv (scFv) antibody fragments. They selected six different scFv mutants with five consensus mutations. However, kinetic analysis of these mutants showed that their antigen-specificity remained similar to that of the wild type. However, they have demonstrated that two of the five consensus mutations were within the complementarity determining regions (CDRs). And they concluded that mRNA display has the potential for rapid artificial evolution of high-affinity diagnostic and therapeutic antibodies by optimizing their CDRs.
Roberts and coworkers have demonstrated that unnatural peptide oligomers consisting of an N-substituted amino acid can be synthesized as mRNA-polypeptide fusions. N-substituted amino acid-containing peptides have been associated with good proteolytic stability and improved pharmacokinetic properties. This work indicates that mRNA display technology has the potential for selecting drug-like peptides for therapeutic usage resistant to proteolysis.