Recombinant protein therapy articles within Nature Communications

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  • Article
    | Open Access

    Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.

    • Claudia L. Driscoll
    • , Anthony H. Keeble
    •  & Mark R. Howarth

  • Article
    | Open Access

    The recent emergence of monoclonal antibodies able to neutralize snake toxins have revolutionized the approach of developing novel therapies to treat snakebite envenoming, at least in animal models. Here, the authors show antibody-dependent enhancement of toxicity (ADET) for a toxin derived from snake venom and highlight the importance of this phenomenon when testing therapeutic antibodies against snake venoms in animal models.

    • Christoffer V. Sørensen
    • , Julián Fernández
    •  & Andreas H. Laustsen

  • Article
    | Open Access

    IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgETRAP and show reduction of mast cell and IgE levels in models of food allergy.

    • Seong Beom An
    • , Bo-Gie Yang
    •  & Myoung Ho Jang

  • Article
    | Open Access

    Cancers often harbor mutations in genes encoding important regulatory proteins, but therapeutic targeting of these molecules proves difficult due to their high structural similarity to their non-mutated counterpart. Here authors show the engineering of T cell engaging bispecific protein able to selectively target cancer cells with a high-frequency mutation in the KRAS oncogene.

    • Andrew Poole
    • , Vijaykumar Karuppiah
    •  & Chandramouli Chillakuri

  • Article
    | Open Access

    Excess ketogenesis can lead to ketoacidosis, a serious complication in patients with diabetes. Here the authors report an insulin independent pathway, the hepatic nonparenchymal S100A9-TLR4-mTORC1 axis, that is able to normalize diabetic ketogenesis and pre-clinical data to suggest potential for development of S100A9 based adjunctive therapy to insulin.

    • Gloria Ursino
    • , Giorgio Ramadori
    •  & Roberto Coppari

  • Article
    | Open Access

    CD28 costimulatory signalling can be suppressed by immune checkpoints, such as CTLA-4 and PD-1. Here the authors describe the design of the fusion therapeutic davoceticept (ALPN-202), based on a variant CD80 extracellular domain engineered to bind PD-L1 as well as CD28 and CTLA-4, providing direct T cell costimulation and dual checkpoint inhibition to enable anti-tumor immune responses.

    • Mark F. Maurer
    • , Katherine E. Lewis
    •  & Stanford L. Peng

  • Article
    | Open Access

    Primary congenital glaucoma (PCG) is characterised by increased intraocular pressure, and variants in ANGPT1, or SVEP1 have been identified as risk alleles. Here, the authors show that deletion of these genes induces glaucoma in mice, and that activation of ANGPT1-TEK signaling ameliorates disease progression in mouse models.

    • Benjamin R. Thomson
    • , Pan Liu
    •  & Susan E. Quaggin

  • Article
    | Open Access

    Oncogenic RAS mutants remain difficult to target with small molecules. Here, the authors show that RAS-binding Affimer proteins inhibit RAS signaling while binding diverse regions on the RAS surface, suggesting the potential to use Affimers as tools to identify new binding pockets and pharmacophores.

    • Katarzyna Z. Haza
    • , Heather L. Martin
    •  & Darren C. Tomlinson

  • Article
    | Open Access

    Bispecific antibodies have been generated in many different formats and it is becoming clear that rational design alone cannot create optimal functionalities. Here the authors introduce the high throughput methodology, Format Chain Exchange (FORCE), to enable combinatorial generation of bispecific antibodies.

    • Stefan Dengl
    • , Klaus Mayer
    •  & Ulrich Brinkmann

  • Article
    | Open Access

    SARS-CoV-2 uses ACE2 as the entry receptor. Here, the authors show that an ACE2-Ig fusion protein inhibits entry of virus pseudotyped with the SARS-CoV-2 spike protein, show differential binding kinetics of SARS-CoV and SARSCoV-2 spike proteins to ACE2, and determine pharmakocinetic parameters of ACE2-Ig in mice.

    • Changhai Lei
    • , Kewen Qian
    •  & Shi Hu

  • Article
    | Open Access

    The use of enzymes as drugs requires that they persist within target tissues over therapeutically relevant time frames. Here the authors use a galectin-3 fusion to anchor enzymes at injection sites for up to 14 days.

    • Shaheen A. Farhadi
    • , Evelyn Bracho-Sanchez
    •  & Gregory A. Hudalla

  • Article
    | Open Access

    Several therapeutics are glycosylated proteins, yet the analysis of their specific glycosylation patterns remains challenging. Here the authors demonstrate an approach for the detailed characterization of glycosylated biopharmaceuticals applied to the determination of the glycoproteoform profile of glycoengineered variants of erythropoietin.

    • Tomislav Čaval
    • , Weihua Tian
    •  & Albert J. R. Heck

  • Article
    | Open Access

    The ability to combine the production of multiple biologics into a single ‘on demand’ system could help in situations where resources are limited. Here the authors demonstrate a proof-of-concept approach for the co-production of three biologics, allowing singular, mixed and combination drug products.

    • Jicong Cao
    • , Pablo Perez-Pinera
    •  & Timothy K. Lu

  • Article
    | Open Access

    Humans are less sensitive to the therapeutic effects of botulinum neurotoxin B (BoNT/B) than the animal models it is tested on due to differences between the human and the mouse receptors. Here, the authors engineer BoNT/B to improve its affinity to human receptors and enhance its therapeutic efficacy.

    • Liang Tao
    • , Lisheng Peng
    •  & Min Dong

  • Article
    | Open Access

    The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is a promising therapeutic target. Here the authors characterize the assembly mechanism of the receptor complex driven by human TSLP, and its antagonism by the monoclonal antibody Tezepelumab and a fusion protein comprising the TSLP receptors.

    • Kenneth Verstraete
    • , Frank Peelman
    •  & Savvas N. Savvides

  • Article
    | Open Access

    The inorganic procoagulant polymer polyphosphate participates in thrombosis via factor XII. Here the authors use recombinant probes that specifically bind or degrade circulating polyphosphate to protect mice in arterial and venous thrombosis models without an increased bleeding risk, the primary complication of all currently used anticoagulants.

    • Linda Labberton
    • , Ellinor Kenne
    •  & Thomas Renné

  • Article
    | Open Access

    Generalized arterial calcification of infancy (GACI) is a terminal disease caused by the ENPP1 enzyme deficiency. Here, Albrigh et al. show that ENPP1 enzyme replacement therapy prevents the ectopic calcifications and mortality in mice with GACI, suggesting a novel treatment for vascular calcification in humans.

    • Ronald A. Albright
    • , Paul Stabach
    •  & Demetrios T. Braddock

  • Article |

    MG53 acts as a membrane repair protein in striatal muscle. Here the authors report that MG53 is also expressed in the lung, where it exerts a similar repair function in the context of pulmonary epithelial damage, and show that administration of recombinant MG53 ameliorates lung injury in mice.

    • Yanlin Jia
    • , Ken Chen
    •  & Jianjie Ma

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