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

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

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

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

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

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

Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature

Acknowledgements The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC) (S3802ASA) and the generous support of the Martin Family Foundation for funding the Ph.D. studentships of P. S. and A. L., respectively. This work was also partially funded through a US-Ireland R&D Partnership grant awarded by HSCNI (STL/5010/14), Medical Research Council UK (MC_PC_15013), and the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R009112/1).Peer reviewedPublisher PD

Oriented attachment of VNAR proteins, Q2 via site-selective modification, on PLGA–PEG nanoparticles enhances nanoconjugate performance

This work was partially funded through a US-Ireland R&D Partnership grant (STL/5010/14, MRC grant MC_PC_15013). JCFN is funded by the EU’s Horizon 2020 programme under Marie-Curie grant agreement 675007. We acknowledge UCL Chemistry Mass Spectrometry Facility (Dr K. Karu/Dr X. Yang).Peer reviewedPublisher PDFsupplementary_dat

Niche-specific regulation of central metabolic pathways in a fungal pathogen

To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis