Structural insights and biomedical potential of IgNAR scaffolds from sharks

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In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Constructs in a Mouse Model of Human RA : An Encouraging Milestone to Further Clinical Drug Development

Funding Information: The authors wish to acknowledge the funding support for this work from Scottish Enterprise (SE) (VNAR_001 (2012)), the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/K010905/1), and Innovate UK (102865).Peer reviewedPublisher PD

Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralising Potency and Multifunctionality, Generated for Therapeutic Development

ACKNOWLEDGMENTS The authors wish to acknowledge the funding support for this work from MSD/Scottish Universities Life Sciences Alliance (SULSA), Scottish Enterprise, the Biotechnology and Biological Sciences Research Council (BBSRC), and the University of Aberdeen. FUNDING Grateful for support from Biotechnology and Biological Sciences Research Council (BB/K010905/1), Scottish Enterprise [VNAR_001 (2012)], Scottish Universities Life Sciences Alliance/ MSD (MSD01_A_Porter-Teismann), and the College of Life Sciences and Medicine, University of Aberdeen (Fee bursary to OU).Peer reviewedPublisher PD

Isolation of highly selective IgNAR variable single-domains against a human therapeutic Fc scaffold and their application as tailor-made bioprocessing reagents

Funding This work was supported by the Industrial Biotechnology Innovation Centre, and Merck KGaA. Acknowledgements The authors would like to thank Iris Willenbücher and Kerstin Hallstein for the BIAcore™ analysis and Nadine Barron for the bio-layer interferometry work.Peer reviewedPostprin

Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy

Chronic liver disease results in a liver-scarring response termed fibrosis. Excessive scarring leads to cirrhosis, which is associated with high morbidity and mortality. The only treatment for liver cirrhosis is liver transplantation; therefore, much attention has been directed toward therapies that will slow or reverse fibrosis. Although anti-fibrogenic therapies have been shown to be effective in experimental animal models, licensed therapies have yet to emerge. A potential problem for any anti-fibrogenic therapy in the liver is the existence of the body’s major drug metabolising cell (the hepatocyte) adjacent to the primary fibrosis-causing cell, the myofibroblast. This article reviews the development of a human recombinant single-chain antibody (scAb) that binds to the surface of myofibroblasts. This antibody binds specifically to myofibroblasts in fibrotic mouse livers. When conjugated with a compound that stimulates myofibroblast apoptosis, the antibody directs the specific apoptosis of myofibroblasts with greater specificity and efficacy than the free compound. The antibody also reduces the adverse effect of liver macrophage apoptosis and—in contrast to the free compound—reversed fibrosis in the sustained injury model used. These data suggest that specifically stimulating the apoptosis of liver myofibroblasts using a targeting antibody has potential in the treatment of liver fibrosis

In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development

Acknowledgments: The authors would like to acknowledge the funding support for this work from Scottish Enterprise [VNAR_001(2012)] and the Biotechnology and Biological Sciences Research Council (BB/K010905/1).Peer reviewedPublisher PD

An Anti-hTNF-α Variable New Antigen Receptor Format Demonstrates Superior in vivo Preclinical Efficacy to Humira® in a Transgenic Mouse Autoimmune Polyarthritis Disease Model

Funding The Biotechnology and Biological Sciences Research Council (BB/K010905/1), Scottish Enterprise (VNAR_001 (2012), Innovate UK (102865). Acknowledgments The authors wish to acknowledge the funding support for this work from Scottish Enterprise (SE), the Biotechnology and Biological Sciences Research Council (BBSRC), and Innovate UK.Peer reviewedPublisher PD

Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand

Acknowledgments Supported by an unrestricted departmental grant from Research to Prevent Blindness (New York, NY), NEI K08EY023998 (KLP), P30-EY001730 (RVG; Bethesda, MD), by a grant from Elasmogen Limited (RVG), and with support from the Mark J. Daily, MD Research Fund (RVG, KLP).Peer reviewedPublisher PD

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD