What still needs to be achieved?
At present, peptide display technologies are limited to the largescale screening of soluble recombinant targets or target fragments. This either misses significant target classes such as membrane bound proteins or results in their screening under non-native conditions which may limit the relevancy of any hits obtained.
The screening of cell-surface targets presents a significant hurdle for all display technologies. Yeast, bacteria and phage display suffer from non-specific interactions with cells while mRNA display has problems due to the instability of the mRNA. Furthermore, direct screening of peptide libraries for a functional cellular response would require peptides at sufficient concentrations to elicit a response from target, something not possible when only presenting a single copy of the peptide with mRNA or 5 to 7 copies with phage display. However, when using display platforms that present high copy numbers of peptide functional cell screening becomes a realistic prospect.
Cell based functional screening models can have a significant impact on peptide display technologies and peptide therapeutic discovery by deconvoluting specific and nonspecific binders or functional from non-functional binders at the primary screening step, resulting in significant time and cost savings.