Cell-free translation of peptides and proteins:from high throughput screening to clinical production

In the past decade, in vitro transcription/translation technologies have emerged as discovery tools for screening large protein expression libraries, for the selection of engineered polypeptide libraries, and as alternatives to conventional heterologous expression for protein production. Therapeutic proteins and peptides discovered using ribosome-based display methods that link genetic information to the encoded polypeptide generated by cell-free extracts, or purified translation components, are beginning to move forward into human clinical trials. This review details the significant progress in in vitro translation for novel protein and non-natural amino acid containing peptide discovery platforms, as well as advances in the clinical-scale production of therapeutic proteins using cell-free transcription/translation.

► Recent advances in cell-free translation display are reviewed
► Genetic code expansion yields peptides with small-molecule drug-like properties.
► Molecules identified by translation display are moving into clinical trials.
► Cell-free protein synthesis is an integrated platform for therapeutic development.