COSMIX uses mRNA display technology, which is a technique for generating and identifying new peptides with tailored functions. The in vitro process initially creates vast numbers of peptide molecules. Then, improvements of known peptide function are directed by evolutionary pressure and repeated rounds of selection cycles.
The revolutionary process involves modifying the RNA molecule used for the production of peptide by in vitro translation in a way that it chemically binds to the synthesized peptide.

The technology involves the use of covalently linked mRNA-peptide fusions as a simple and stable method for linking the genetic information (genotype) to the function of the corresponding protein (phenotype).

Initially mRNA is modified by attaching a DNA linker carrying a puromycin-like moiety at its end. This is accomplished by a template-directed cross-link of a synthetic oligonucleotide bearing a 3'-terminal Puromycin-like MHA residue.
After readthrough of the open reading frame of the message the Puromycin-like MHA acceptor moiety is recognized by the ribosome and incorporated into the nascent polypeptide chain to generate the mRNA-peptide-fusion.

Starting off with mRNA-peptide fusions libraries with a variability of up to 100,000 billion candidates immobilized targets are contacted with the libraries, washed and the binding candidates are recovered by subsequent reverse transcription and PCR amplification.
This allows the selection step to be repeated and by raising the stringency of the desired criteria during multiple rounds of selection, peptides with high affinities to the specified target can be enriched, cloned and sequenced.
The selected peptides can then be produced synthetically. Usually 6–10 selection rounds are performed to enrich high affinity peptide binders with (sub) nanomolar affinities.