Science & Insights

@article{Diaz2025,

title = {SARS-CoV-2 spike peptide analysis reveals a highly conserved region that elicits potentially pathogenic autoantibodies: implications to pan-coronavirus vaccine development},

author = {Marilyn Diaz and Zbignew Mikulski and Dan Leaman and Angel Gandarilla and Nathalia Da Silva and Annie Verkoczy and Jinsong Zhang and Laurent Verkoczy},

url = {https://trenzyme.com/protein-production-services/custom-protein-expression-service/, ➥Custom Protein Expression Service

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doi = {10.3389/fimmu.2025.1488388},

issn = {1664-3224},

year  = {2025},

date = {2025-02-25},

urldate = {2025-02-25},

journal = {Front. Immunol.},

volume = {16},

publisher = {Frontiers Media SA},

abstract = {The SARS-CoV-2 pandemic, while subsiding, continues to plague the world as new variants emerge. Millions have died, and millions more battle with the debilitating symptoms of a clinical entity known as long Covid. The biggest challenge remains combating an ever-changing variant landscape that threatens immune evasion from vaccine and prior infection-generated immunity. In addition, the sequelae of symptoms associated with long Covid almost certainly point to multiple pathologies that range from direct damage to organs during infection to a potential role for infection-induced autoreactive antibodies in promoting autoimmune-like conditions in these patients. In this study, a peptide scan of the SARS-CoV-2 spike protein was done to detect novel, highly conserved linear epitopes that do not elicit autoantibodies. We identified eight predicted linear epitopes capable of eliciting anti-spike IgG antibodies. Immunizations alternating peptide conjugated to KLH with the full trimer yielded the highest antibody levels, but homologous immunization with some of the peptides also yielded high levels when an additional immunization step was added. Of all regions tested, the stem helix adjacent to the heptad repeat 2 (HR2) region also elicited high levels of autoreactive antibodies to known autoantigens in common systemic autoimmune disorders such as lupus and scleroderma and may contribute to the long Covid syndrome seen in some patients. Implications to vaccine design are discussed.},

keywords = {P2020-022, P2020-029, SARS-CoV-2},

pubstate = {published},

tppubtype = {article}

}

@article{Vázquez-Díaz2025,

title = {Dual-Mode Immunosensor for Antibody Detection: Harnessing the Versatility of Antibody-Based Nanozymes across Optical and Electrochemical Platforms},

author = {Silvia Vázquez-Díaz and Laura Saa and David Otaegui and Valeri Pavlov and Asis Palazón and Aitziber L. Cortajarena},

url = {https://trenzyme.com/protein-production-services/custom-protein-expression-service/, ➥Custom Protein Expression Service

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doi = {10.1021/acs.analchem.4c05317},

issn = {1520-6882},

year  = {2025},

date = {2025-02-18},

urldate = {2025-02-18},

journal = {Anal. Chem.},

volume = {97},

number = {6},

pages = {3361--3370},

publisher = {American Chemical Society (ACS)},

abstract = {In the early years of the 21st century, numerous viral infectious diseases have proliferated, prompting intensified efforts to devise more effective diagnostic methods. In response, various biosensors have emerged with the aim of overcoming the constraints of conventional diagnostic techniques. Nanomaterial-based biosensors have revolutionized conventional approaches, significantly enhancing biosensor performance and effectively tackling these challenges. A diverse array of nanoparticles and nanomaterials has been systematically synthesized, engineered, and employed to augment the functionalities of biosensors. This work capitalizes on the properties of gold–platinum bimetallic nanoclusters (NCs) embedded in the structure of an immunoglobulin (IgG) (Au/Pt NCs-IgG), unveiling a novel double strategy for the detection of antibodies that leverages both their catalytic NC scaffold and the biorecognition element. The detection mechanism revealed the unique oxidase-like properties of Au/Pt NCs-IgG. This distinctive property, in addition to previously reported peroxidase-like activity, positions Au/Pt NCs-IgG as an effective probe in both optical and electrochemical sandwich enzyme-linked immunosorbent assays, facilitating their incorporation in different sensor frameworks and their utilization across various applications. As a study case, anti-SARS-CoV-2 antibodies (anti-RBD IgG antibodies) were employed as the target analyte. A linear detection range was found between 0.5 and 100 ng/mL for optical immunosensors and 50–300 ng/mL for electrochemical immunosensors. The validation of the immunosensor in clinical samples demonstrated its promising diagnostic value. The significantly differential signal obtained between positive and negative clinical samples underscores the suitability of both sensors for point-of-care diagnostic applications.},

keywords = {Au/Pt NCs-IgG, P2020-001, P2020-100, SARS-CoV-2},

pubstate = {published},

tppubtype = {article}

}

@article{Mosca2025,

title = {Standardization of hemoglobin A2 and hemoglobin F: Achievements and perspectives},

author = {Andrea Mosca and Cristian-Gabriel Arsene and Renata Paleari and Patricia Kaiser and Kees Harteveld and Yvonne Daniel and Chie Amano and Atsushi Murakami and Guy Auclair},

url = {https://trenzyme.com/protein-production-services/custom-protein-expression-service/, ➥Custom Protein Expression Service

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doi = {10.1016/j.cca.2024.120087},

issn = {0009-8981},

year  = {2025},

date = {2025-02-00},

urldate = {2025-02-00},

journal = {Clinica Chimica Acta},

volume = {567},

publisher = {Elsevier BV},

abstract = {The establishment of reference systems for the standardization of hemoglobin A2 (HbA2) and fetal hemoglobin (HbF), both critical for improving diagnostic accuracy in conditions such as β-thalassemia and sickle cell disease, are described. Efforts were led by the IFCC and other groups to address and reduce the variability in laboratory measurements of these hemoglobins. This document outlines the production of certified reference materials (CRMs) for HbA2 and the development of a reference measurement procedure using isotope dilution mass spectrometry. Similarly, standardizing HbF is essential for supporting diagnostic and therapeutic strategies, particularly in managing sickle cell disease. HbF levels can predict disease outcomes and guide treatment plans. Significant challenges remain in achieving consistent measurement across laboratories, and the process for standardization for this minor hemoglobin has just begun. We are confident that the implementation of these reference systems will provide improved accuracy and traceability in the future.},

keywords = {HbA2, HbF, P2020-193, P2020-199},

pubstate = {published},

tppubtype = {article}

}

@article{Hoffmann2024,

title = {Discovery of Carbonic Anhydrase 9 as a Novel CLEC2 Ligand in a Cellular Interactome Screen},

author = {Sebastian Hoffmann and Benedict-Tilman Berger and Liane Rosalie Lucas and Felix Schiele and John Edward Park},

url = {https://trenzyme.com/protein-production-services/custom-protein-expression-service/, ➥Custom Protein Expression Service},

doi = {10.3390/cells13242083},

issn = {2073-4409},

year  = {2024},

date = {2024-12-00},

urldate = {2024-12-00},

journal = {Cells},

volume = {13},

number = {24},

publisher = {MDPI AG},

abstract = {Membrane proteins, especially extracellular domains, are key therapeutic targets due to their role in cell communication and associations. Yet, their functions and interactions often remain unclear. This study presents a general method to discover interactions of membrane proteins with immune cells and subsequently to deorphanize their respective receptors. We developed a comprehensive recombinant protein library of extracellular domains of human transmembrane proteins and proteins found in the ER-Golgi-lysosomal systems. Using this library, we conducted a flow-cytometric screen that identified several cell surface binding events, including an interaction between carbonic anhydrase 9 (CAH9/CA9/CAIX) and CD14high cells. Further analysis revealed this interaction was indirect and mediated via platelets bound to the monocytes. CA9, best known for its diverse roles in cancer, is a promising therapeutic target. We utilized our library to develop an AlphaLISA high-throughput screening assay, identifying CLEC2 as one robust CA9 binding partner. A five-amino-acid sequence (EDLPT) in CA9, identical to a CLEC2 binding domain in Podoplanin (PDPN), was found to be essential for this interaction. Like PDPN, CA9-induced CLEC2 signaling is mediated via Syk. A Hodgkin’s lymphoma cell line (HDLM-2) endogenously expressing CA9 can activate Syk-dependent CLEC2 signaling, providing enticing evidence for a novel function of CA9 in hematological cancers. In conclusion, we identified numerous interactions with monocytes and platelets and validated one, CA9, as an endogenous CLEC2 ligand. We provide a new list of other putative CA9 interaction partners and uncovered CA9-induced CLEC2 activation, providing new insights for CA9-based therapeutic strategies.},

keywords = {CLEC2},

pubstate = {published},

tppubtype = {article}

}

@article{Lant2024,

title = {Poxin-deficient poxviruses are sensed by cGAS prior to genome replication},

author = {Sian Lant and Alasdair J. M. Hood and Joe A. Holley and Ailish Ellis and Lucy Eke and Rebecca P. Sumner and David O. Ulaeto and Carlos Maluquer de Motes},

url = {https://trenzyme.com/protein-production-services/custom-protein-expression-service/, ➥Custom Protein Expression Service},

doi = {10.1099/jgv.0.002036},

issn = {1465-2099},

year  = {2024},

date = {2024-10-21},

urldate = {2024-10-21},

journal = {General Virology},

volume = {105},

number = {10},

publisher = {Microbiology Society},

abstract = {Poxviruses are dsDNA viruses infecting a wide range of cell types, where they need to contend with multiple host antiviral pathways, including DNA and RNA sensing. Accordingly, poxviruses encode a variety of immune antagonists, most of which are expressed early during infection from within virus cores before uncoating and genome release take place. Amongst these antagonists, the poxvirus immune nuclease (poxin) counteracts the cyclic 2′3′-GMP-AMP (2′3′-cGAMP) synthase (cGAS)/stimulator of interferon genes DNA sensing pathway by degrading the immunomodulatory cyclic dinucleotide 2′3′-cGAMP, the product of activated cGAS. Here, we use poxviruses engineered to lack poxin to investigate how virus infection triggers the activation of STING and its downstream transcription factor interferon-responsive factor 3 (IRF3). Our results demonstrate that poxin-deficient vaccinia virus (VACV) and ectromelia virus (ECTV) induce IRF3 activation in primary fibroblasts and differentiated macrophages, although to a lower extent in VACV compared to ECTV. In fibroblasts, IRF3 activation was detectable at 10 h post-infection (hpi) and was abolished by the DNA replication inhibitor cytosine arabinoside (AraC), indicating that the sensing was mediated by replicated genomes. In macrophages, IRF3 activation was detectable at 4 hpi, and this was not affected by AraC, suggesting that the sensing in this cell type was induced by genomes released from incoming virions. In agreement with this, macrophages expressing short hairpin RNA (shRNA) against the virus uncoating factor D5 showed reduced IRF3 activation upon infection. Collectively, our data show that the viral genome is sensed by cGAS prior to and during genome replication, but immune activation downstream of it is effectively suppressed by poxin. Our data also support the model where virus uncoating acts as an immune evasion strategy to simultaneously cloak the viral genome and allow the expression of early immune antagonists.},

keywords = {IRF3},

pubstate = {published},

tppubtype = {article}

}