Highest Quality Protein Library : Retrogenix

Highest quality protein library

A more comprehensive screen

Human cell microarray technology has long been the leading tool for discovering primary receptors and assessing potential off-target binding against expressed human proteins. Over a decade of continual development has ensured that the Retrogenix library is of the highest quality. Initially representing only plasma membrane monomers, the Retrogenix library now, uniquely, includes cell surface heterodimers as well as secreted proteins that have been identified as key off-targets for screening through our close collaborations with toxicology teams at leading pharmaceutical companies. Our rigorous bioinformatics approach ensures that miscategorised proteins are always excluded from our library, safeguarding the specificity of our results and providing clients with the confidence that real targets will discovered and won’t be masked by a raft of false positives.

Building the best

After >10 years of expansion and refinement, the Retrogenix cell microarray libraries now have >6,200 proteins for screening. This is the largest set of plasma membrane and secreted proteins expressed in human cells. As data from our specificity screens are frequently used to support IND / BLA submissions it is crucial that we always ensure our technology retains its high success rates as our capabilities continue to grow. The high degree of confidence that clients have when assessing the specificity of a novel biotherapeutic or cell therapy using Retrogenix has allowed many of them to move away from tissue cross reactivity studies altogether. Currently >86% of high confidence plasma membrane proteins are included in the Retrogenix platform, providing excellent coverage across the major sub-classes of cell surface proteins.

Graph of plasma membrane coverage

Tethering ‘secreted’ proteins

As secreted proteins are not naturally localised on the cell surface, novel cDNA constructs have been developed which result in expression of ‘secreted’ proteins fused to inert transmembrane and intracellular domains. As these proteins are tethered to the membrane, binding can be detected using the same workflow as the plasma membrane library. Our bioinformatics collaboration on this project resulted in a ‘high confidence’ list of secreted proteins being generated, for priority inclusion in the library. Of these, >90% are now expressed in the Retrogenix collection, with more under development. Retrogenix continues to innovate and develop its technology to broaden the applications of its platform and provide valuable data that informs both Discovery and safety assessment.

Graph of secreted proteins

Unique to Retrogenix:

Interactions with heterodimers

Retrogenix’s cell microarrary technology has been optimised to allow co-expression of multiple protein subunits, allowing interactions with heterodimeric proteins to be more readily detected. Over 370+ plasma membrane receptor complexes are now expressed within the platform. Read our integrin & CD3 interactions case study to find out more.

Heterodimers – download poster

Screening the secretome

Extensive testing and validation work has confirmed that binding of known ligand:secreted protein pairs can be identified consistently using Retrogenix. Screening for off-target interactions against proteins that are usually secreted from the cell is a unique feature of the Retrogenix platform. See our poster for more details.

Secreted library – download poster

Find out how our specificity screening data are used in IND / BLA submissions

Regulatory submissions

…working with you was exactly like working with an experienced and knowledgeable scientific collaborator. We had the same types of discussions and strategic planning sessions and I felt confident throughout that we were addressing the issues in the best way possible. It was fun and if I see the opportunity we would do this again.

Professor Mark Kahn, University of Pennsylvania

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