Charles River High Peak
TypePublic
IndustryBiotechnology
FoundedSheffield, UK (2008)
FoundersDr. Jim Freeth, Jo Soden
ProductsHuman Cell Microarray Screening (Service)
Number of employees
11-50
Websitewww.criver.com

Retrogenix is a biotechnology company based in the United Kingdom. Founded by Jim Freeth and Jo Soden in 2008, the company was acquired in April 2021 by Charles River Laboratories and is now known as the ‘High Peak’ site.

Research and development

The human Cell Microarray tool developed by Retrogenix utilises a library of expression vectors containing open reading frames (ORFs) encoding full-length human plasma membrane proteins, as well as a green fluorescent protein (GFP). Each vector is combined with a lipid, and the complexes are spotted in precise locations on specialized slides. Reverse transfection of human cells, which are grown on the microarray slides, results in over-expression of each membrane protein located over its respective vector spot. Expression of GFP acts as a control to ensure transfection efficiency and to confirm positioning of the spot co-ordinates. Putative receptor targets are identified by assessing gain-of-binding when a test ligand is applied to the cell microarrays. Further tests determine whether the receptor ‘hit’ is reproducible and to confirm specificity to the test ligand. Currently, more than 4,500 proteins are simultaneously expressed in the Cell Microarray system for individual screening.[1] The human expression system allows for correct folding and localisation at the surface of the cell and there are documented cases of biological interactions that are mediated by post-translational modifications being detected using the technology.[2]

Applications in medical research

The Cell Microarray technology identifies targets and receptors that are important in the understanding of normal biological and disease processes.[3] Diverse ligands can be screened using the technology which has led to the discovery of key receptors for malaria proteins[4] and targets that mediate virus binding to human cells.[5]

Target deconvolution

Cell Microarray screening identifies the receptors for biologic molecules that have been selected through phenotypic screening. Notably, in studies led by Medimmune, the technology identified disease-relevant cell surface antigens of promising phenotypic molecules [6] including the identification of TNFR2 as a potential target for cancer immunotherapy.

Off-target profiling

Cell Microarray off-target profiling assesses the specificity of ligands, either prior to clinical testing[7] or to uncover the mechanism of action for an observed adverse event or an unexpected pharmacokinetic profile.

Awards

Retrogenix has twice won the Queen's Awards for Enterprise. The first award was granted for innovation in 2015.[8] This was followed by an award for international trade in 2017.[9]

References

  1. ↑ Freeth, J. "Target Practice". European Biopharmaceutical Review. No. Winter 2014. Samedan Ltd.
  2. ↑ Salanti A, Clausen TM, Agerbæk M, Al Nakouzi N, Dahlbäck M, Oo HZ, Lee S, Gustavsson T, Rich JR, Hedberg BJ, Mao Y, Barington L, Pereira MA, LoBello J, Endo M, Fazli L, Soden J, Wang CK, Sander AF, Dagil R, Thrane S, Holst PJ, Meng L, Favero F, Weiss GJ, Nielsen MA, Freeth J, Nielsen TO, Zaia J, Tran NL, Trent J, Babcook JS, Theander TG, Sorensen PH, Daugaard M (2015). "Targeting human cancer by a glycosaminoglycan binding malaria protein". Cancer Cell. 28 (4): 500–514. doi:10.1016/j.ccell.2015.09.003. PMC 4790448. PMID 26461094.
  3. ↑ "Removing the receptor deconvolution bottleneck". Genetic Engineering and Biotechnology News. Vol. 33, no. 14. August 2013.
  4. ↑ Turner L, Lavstsen T, Berger SS, Wang CW, Petersen JE, Avril M, Brazier AJ, Freeth J, Jespersen JS, Nielsen MA, Magistrado P, Lusingu J, Smith JD, Higgins MK, Theander TG (2013). "Severe malaria is associated with parasite binding to endothelial protein C receptor". Nature. 498 (7455): 502–505. Bibcode:2013Natur.498..502T. doi:10.1038/nature12216. PMC 3870021. PMID 23739325.
  5. ↑ Sosnovtsev SV, Sandoval-Jaime C, Parra GI, Tin CM, Jones RW, Soden J, Barnes D, Freeth J, Smith AW, Green KY (2017). "Identification of human junctional adhesion molecule-1 as a functional receptor for the Hom-1 calicivirus on humans cells". mBio. 8 (1). doi:10.1128/mBio.00031-17. PMC 5312078. PMID 28196955.
  6. ↑ Sandercock AM, Rust S, Guillard S, Sachsenmeier KF, Holoweckyj N, Hay C, Flynn M, Huang Q, Yan K, Herpers B, Price LS, Soden J, Freeth J, Jermutus L, Hollingsworth R, Minter R (2015). "Identification of anti-tumour biologics using primary tumour models, 3-D phenotypic screening and image-based multi-parametric profiling". Molecular Cancer. 14: 147. doi:10.1186/s12943-015-0415-0. PMC 4521473. PMID 26227951.
  7. ↑ Peng H, Nerreter T, Chang J, Qi J, Li X, Karunadharma P, Martinez G, Fallahi M, Soden J, Freeth J, Beerli RR, Grawunder U, Hudecek M & Rader C (2017). "Mining naïve rabbit antibody repertoires by phage display for monoclonal antibodies of therapeutic utility". Journal of Molecular Biology. 429 (19): 2954–2973. doi:10.1016/j.jmb.2017.08.003. PMC 5610937. PMID 28818634.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ "Queen's Awards: Technical flair drives success in niche markets". Financial Times. 21 April 2015.
  9. ↑ "Second Queen's award for High Peak business". Buxton Advertiser. 21 July 2017.
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