DIMA recombinant protein expression system

     One of the key requirements for antibody development is to utilize the protein immunogens that best mimic the native state of the target protein. Most of the druggable targets for antibody-based therapy are membrane proteins, which are notoriously hard to express. DIMA has created the multiple solutions for the membrane protein production. The human proteins are produced using human cell line, HEK293, secretion expression system, so that they can have a good chance to keep their native formation and modifications. 

      To find the best production strategy, we individually study and design expression construct for every membrane protein target.
     For the single transmembrane protein, we use the well-designed ECD fraction to mimic its functional domain.
     For the full length multi-transmembrane proteins, such as GPCR and Claudin series proteins, we invested heavily on new expression and extraction technologies, and developed 5 different solutions to help with different targets.  

DIMA recombinant protein expression system

Two Solutions for Transmembrane Proteins

Extra Cellular Domain (ECD) Protein

Currently almost all the therapeutic antibody drugs target on extra-cellular domain of human membrane proteins or secreted protein molecules. It is challenging and sometimes impossible to express and purify full length transmembrane proteins in native conformation.

The ECD-Fc fusion protein is normally used to overcome this issue especially for the single transmembrane druggable targets.

DIMA constructed over 1000 expression plasmids for different ECD-Fc fusion proteins and used HEK293 mammalian expression system for production.

This not only ensure the authentic posttranslational modifications from mammalian cells, but also have a high chance of obtaining proteins in good solubility and correct folding under standard buffer system.

Multiplpass Transmembrane Protein (MTP) 

For multi-pass transmembrane proteins (MTPs), DIMA Biotech developed 5 different platforms that can be grouped in 2 categories:

  1. Native cell membrane but not pure proteins include Membrane Nanoparticles (MNPs), exosome (EXO) and Virus-like particles (VLPs).
  2. Pure proteins include Detergent and Nanodisc platforms.

All platforms are based on the mammalian expression systems and prepare full-length MTPs in soluble protein products with native conformation and activity. They can be used for the development of highly specific therapies targeting previously intractable targets such as ion channels and transporter.

Platform Flow

Gene Synthesis

Expression Vector Construction

Test Expression

Scale Up Production And Purification

Quality Evaluation And Functional Test

Key advantages

1. Mammalian expression system with authentic posttranslational modifications
2. Serum free medium culturing system: minimize host cell contamination
3. Custom protein and large batch production available

Key applications

1. Native immunogens for therapeutic antibody drug development
2. Native ligand and receptor identification
3. Therapeutic drug In Vitro functional test
4. In Vitro protein functional test
5. Cell based assays