mRNA Display-based Unnatural Protein Development

Development technologies such as unnatural amino acid mutation, unnatural cofactor engineering and computational design are producing proteins with novel functions. However, these proteins usually fail to meet performance targets. The combination of unnatural amino acid mutation and mRNA display technology has created new and useful proteins. CD BioSciences is committed to applying in vitro display technology to the field of protein research, and has accumulated rich experience in screening and guiding protein evolution over the years, which can provide customers with more flexible, fast and cost-effective non-natural protein development services.

Application of Non-natural Proteins

As an important biological macromolecule, protein is an essential material for all organisms to maintain structure and function. In natural state, 20 kinds of natural amino acids (NAAs) can produce natural proteins with diverse structures and functions, but these natural proteins can no longer meet the research needs of protein engineering and protein drug production and other fields, while the insertion of unnatural amino acids (UNAAs) with new side chain groups can endow proteins with new chemical properties, structures and functions, opening the door of new protein engineering, providing biological research Biotherapeutics and synthetic biology provide new approaches.

  • In the field of basic scientific research, some crosslinkable UNAAs have been embedded into proteins to characterize the ligand-receptor interactions between proteins and nucleic acids; It can enhance the optical and thermal stability of protein and be used to construct nanoswitches.
  • In the field of industrial production research, non-natural proteins can be used as new biopolymer materials, protein drugs and covalent macromolecule inhibitors, creating new opportunities for the development and production of material science and medical proteins, such as the synthesis of protein polymers, selenoprotein, phosphorylated protein and antibody-drug conjugates. Therefore, the synthesis of unnatural proteins embedded in UNAAs is a revolutionary step in the development of protein engineering.

Strategies for designing non-natural enzymes and binders.Fig. 1 Strategies for designing non-natural enzymes and binders. (Lechner H, et al., 2018)

Development Techniques of Non-natural Proteins

In the past, the development of non-natural proteins mainly depended on cell systems, but due to the complexity of intracellular metabolic pathways, the product yield was low and the purification steps were cumbersome; Moreover, some UNAAs are not easy to cross the cell membrane barrier and enter the cell, and produce cytotoxicity, thus limiting the efficiency of UNAAs insertion. Now, with the emergence and maturity of cell-free protein synthesis system, in vitro display technology combined with this system, such as mRNA display, can avoid the drawbacks of cell-based development, and has become one of the important means to develop non-natural proteins.

Our Services

The protein discovery platform built by CD BioSciences based on mRNA display technology can introduce non-natural amino acids into the randomly constructed library and further translate functional proteins in vitro. We provide global customers with one-stop service for the development of non-natural proteins. From the construction of DNA library to the verification of the final target molecule, no matter what type of protein: antibody, enzyme, modified protein, etc., you only need to provide project information, and our professional team will design and optimize the best solution to speed up your drug discovery or mechanism research cycle.

Service Features

  • One-stop Service: provide one-stop service from sequence design, transcription, translation, verification and purification.
  • High Throughput: a high-throughput platform for protein development to achieve standardized mass production.
  • High Efficiency: the advanced technology platform ensures the fastest delivery cycle.
  • High Standard: whole process standardized operation and risk control.

CD BioSciences has many years of project development experience in protein discovery. The protein discovery platform based on mRNA display technology can provide customers with services related to the development and screening of various unnatural proteins. If you are interested in our services, please contact us for more details.


  1. Lechner, H., Ferruz, N., & Höcker, B. (2018). Strategies for designing non-natural enzymes and binders. Current opinion in chemical biology, 47, 67–76.
For Research Use Only. Not For Clinical Use.

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