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https://www.readbyqxmd.com/read/29220018/ablynx-s-nanobody-fragments-go-places-antibodies-cannot
#1
Cormac Sheridan
No abstract text is available yet for this article.
December 8, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29216932/nanobodies-targeting-conserved-epitopes-on-the-major-outer-membrane-protein-of-campylobacter-as-potential-tools-for-control-of-campylobacter-colonization
#2
Charlotte Vanmarsenille, Inés Díaz Del Olmo, Jelle Elseviers, Gholamreza Hassanzadeh Ghassabeh, Kristof Moonens, Didier Vertommen, An Martel, Freddy Haesebrouck, Frank Pasmans, Jean-Pierre Hernalsteens, Henri De Greve
Campylobacter infections are among the most prevalent foodborne infections in humans, resulting in a massive disease burden worldwide. Broilers have been identified as the major source of campylobacteriosis and reducing Campylobacter loads in the broiler caeca has been proposed as an effective measure to decrease the number of infections in humans. Failure of current methods to control Campylobacter in broilers stresses the urgency to develop novel mitigation measures. We obtained six nanobodies with a broad specificity, that recognize strains belonging to the two most relevant species, Campylobacter jejuni and Campylobacter coli...
December 8, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29215864/platinum-nanocatalyst-amplification-redefining-the-gold-standard-for-lateral-flow-immunoassays-with-ultra-broad-dynamic-range
#3
Colleen N Loynachan, Michael R Thomas, Eleanor R Gray, Daniel A Richards, Jeongyun Kim, Benjamin S Miller, Jennifer Clare Brookes, Shweta Agarwal, Vijay Chudasama, Rachel A McKendry, Molly M Stevens
Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used point-of-care (PoC) devices, however, their application in early disease diagnostics is often limited due to insufficient sensitivity for the requisite sample sizes and the short timeframes of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labelled LFIA with a sensitivity surpassing that of both current commercial and published sensitivities for paper-based detection of p24, one of the earliest and most conserved biomarkers of HIV...
December 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/29213270/nanobodies-and-nanobody-based-human-heavy-chain-antibodies-as-antitumor-therapeutics
#4
REVIEW
Peter Bannas, Julia Hambach, Friedrich Koch-Nolte
Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29213077/allosteric-nanobodies-uncover-a-role-of-hippocampal-mglu2-receptor-homodimers-in-contextual-fear-consolidation
#5
Pauline Scholler, Damien Nevoltris, Dimitri de Bundel, Simon Bossi, David Moreno-Delgado, Xavier Rovira, Thor C Møller, Driss El Moustaine, Michaël Mathieu, Emilie Blanc, Heather McLean, Elodie Dupuis, Gérard Mathis, Eric Trinquet, Hervé Daniel, Emmanuel Valjent, Daniel Baty, Patrick Chames, Philippe Rondard, Jean-Philippe Pin
Antibodies have enormous therapeutic and biotechnology potential. G protein-coupled receptors (GPCRs), the main targets in drug development, are of major interest in antibody development programs. Metabotropic glutamate receptors are dimeric GPCRs that can control synaptic activity in a multitude of ways. Here we identify llama nanobodies that specifically recognize mGlu2 receptors, among the eight subtypes of mGluR subunits. Among these nanobodies, DN10 and 13 are positive allosteric modulators (PAM) on homodimeric mGlu2, while DN10 displays also a significant partial agonist activity...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29209322/camelid-single-domain-antibodies-historical-perspective-and-future-outlook
#6
Mehdi Arbabi-Ghahroudi
Tremendous effort has been expended over the past two and a half decades to understand many aspects of camelid heavy chain antibodies, from their biology, evolution, and immunogenetics to their potential applications in various fields of research and medicine. In this article, I present a historical perspective on the development of camelid single-domain antibodies (sdAbs or VHHs, also widely known as nanobodies) since their discovery and discuss the advantages and disadvantages of these unique molecules in various areas of research, industry, and medicine...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29207143/screening-and-antitumor-effect-of-an-anti%C3%A2-ctla%C3%A2-4-nanobody
#7
Ruirong Wan, Aiqun Liu, Xiaoqiong Hou, Zongqiang Lai, Jieping Li, Nuo Yang, Juntao Tan, Fengzhen Mo, Zixi Hu, Xiaomei Yang, Yongxiang Zhao, Xiaoling Lu
Cytotoxic T‑lymphocyte antigen‑4 (CTLA‑4) is a critical negative regulator of immune responses. CTLA‑4 is rapidly upregulated following T‑cell activation, and then binds to B7 molecules with a higher affinity than CD28. CTLA‑4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regulatory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA‑4 activity for enhancing immune responses against cancer...
December 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29177623/expression-of-single-domain-antibody-in-different-systems
#8
REVIEW
Yongkang Liu, He Huang
Camelid single-domain antibodies (sdAbs, VHHs, or Nanobodies®) are types of antibody fragments that are composed of the heavy-chain variable domain only. These VHHs possess unique structural and functional features, as they are small in size and exhibit thermal stability and high solubility. Compared to conventional antibodies, VHHs can be manufactured in microorganisms to significantly save on cost, labor, and time since VHHs lack the Fc domain with its N-linked oligosaccharide. Until now, VHHs have been expressed in several kinds of production systems, ranging from prokaryotic cells, yeasts, fungi, insect cells, and mammalian cell lines, to plants...
November 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29176642/insight-into-partial-agonism-by-observing-multiple-equilibria-for-ligand-bound-and-gs-mimetic-nanobody-bound-%C3%AE-1-adrenergic-receptor
#9
Andras S Solt, Mark J Bostock, Binesh Shrestha, Prashant Kumar, Tony Warne, Christopher G Tate, Daniel Nietlispach
A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., Gs and β-arrestin. Using 13C methyl methionine NMR for the β1-adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with Gs-mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody-receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism...
November 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163515/nanobody-based-delivery-systems-for-diagnosis-and-targeted-tumor-therapy
#10
REVIEW
Yaozhong Hu, Changxiao Liu, Serge Muyldermans
The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma's, monoclonal antibodies (mAbs) have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29160309/structure-of-pink1-in-complex-with-its-substrate-ubiquitin
#11
Alexander F Schubert, Christina Gladkova, Els Pardon, Jane L Wagstaff, Stefan M V Freund, Jan Steyaert, Sarah L Maslen, David Komander
Autosomal recessive juvenile Parkinsonism (AR-JP) is caused by mutations in a number of PARK genes, in particular in the E3 ubiquitin ligase Parkin (PARK2), and in its upstream protein kinase PINK1 (PARK6). PINK1 phosphorylates ubiquitin and the Parkin ubiquitin-like domain on structurally protected Ser65 to trigger mitophagy. We here report a crystal structure of a nanobody-stabilised complex between Pediculus humanus corporis (Ph)PINK1 with ubiquitin in the 'C-terminally retracted' (Ub-CR) conformation. The structure reveals many peculiarities of PINK1, including the architecture of the C-terminal region, and reveals how the PINK1 N-lobe binds ubiquitin via a unique insertion...
October 30, 2017: Nature
https://www.readbyqxmd.com/read/29160134/surfactant-protein-a-nanobody-conjugated-liposomes-loaded-with-methylprednisolone-increase-lung-targeting-specificity-and-therapeutic-effect-for-acute-lung-injury
#12
Nan Li, Dong Weng, Shan-Mei Wang, Yuan Zhang, Shan-Shan Chen, Zhao-Fang Yin, Jiali Zhai, Judy Scoble, Charlotte C Williams, Tao Chen, Hui Qiu, Qin Wu, Meng-Meng Zhao, Li-Qin Lu, Xavier Mulet, Hui-Ping Li
The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29137184/cell-type-specific-metabolic-flux-analysis-a-challenge-for-metabolic-phenotyping-and-a-potential-solution-in-plants
#13
Merja T Rossi, Monika Kalde, Chaiyakorn Srisakvarakul, Nicholas J Kruger, R George Ratcliffe
Stable isotope labelling experiments are used routinely in metabolic flux analysis (MFA) to determine the metabolic phenotype of cells and tissues. A complication arises in multicellular systems because single cell measurements of transcriptomes, proteomes and metabolomes in multicellular organisms suggest that the metabolic phenotype will differ between cell types. In silico analysis of simulated metabolite isotopomer datasets shows that cellular heterogeneity confounds conventional MFA because labelling data averaged over multiple cell types does not necessarily yield averaged flux values...
November 13, 2017: Metabolites
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#14
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116505/construction-of-high-quality-camel-immune-antibody-libraries
#15
Ema Romão, Vianney Poignavent, Cécile Vincke, Christophe Ritzenthaler, Serge Muyldermans, Baptiste Monsion
Single-domain antibodies libraries of heavy-chain only immunoglobulins from camelids or shark are enriched for high-affinity antigen-specific binders by a short in vivo immunization. Thus, potent binders are readily retrieved from relatively small-sized libraries of 10(7)-10(8) individual transformants, mostly after phage display and panning on a purified target. However, the remaining drawback of this strategy arises from the need to generate a dedicated library, for nearly every envisaged target. Therefore, all the procedures that shorten and facilitate the construction of an immune library of best possible quality are definitely a step forward...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29107128/targeted-cancer-therapy-through-antibody-fragments-decorated-nanomedicines
#16
REVIEW
Abbas Alibakhshi, Fatemeh Abarghooi Kahaki, Shahrzad Ahangarzadeh, Hajar Yaghoobi, Fatemeh Yarian, Roghaye Arezumand, Javad Ranjbari, Ahad Mokhtarzadeh, Miguel de la Guardia
Active targeting in cancer nanomedicine, for improved delivery of agents and diagnose, has been reviewed as a successful way for facilitating active uptake of theranostic agents by the tumor cells. The application of a targeting moiety in the targeted carrier complexes can play an important role in differentiating between tumor and healthy tissues. The pharmaceutical carriers, as main part of complexes, can be polymeric nanoparticles, micelles, liposomes, nanogels and carbon nanotubes. The antibodies are among the natural ligands with highest affinity and specificity to target pharmaceutical nanoparticle conjugates...
November 3, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29095961/nanobodies-targeting-norovirus-capsid-reveal-functional-epitopes-and-potential-mechanisms-of-neutralization
#17
COMPARATIVE STUDY
Anna D Koromyslova, Grant S Hansman
Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29095202/simultaneous-inhibition-of-tumor-necrosis-factor-receptor-1-and-matrix-metalloproteinase-8-completely-protects-against-acute-inflammation-and-sepsis
#18
Sophie Steeland, Sara Van Ryckeghem, Jolien Vandewalle, Marlies Ballegeer, Elien Van Wonterghem, Melanie Eggermont, Johan Decruyenaere, Liesbet De Bus, Claude Libert, Roosmarijn E Vandenbroucke
OBJECTIVES: Sepsis causes very high mortality and morbidity rates and remains one of the biggest medical challenges. This study investigates whether plasma levels of both matrix metalloproteinase 8 and tumor necrosis factor receptor 1 are associated with sepsis severity and also investigates the therapeutic applicability of simultaneous inhibition of the two molecules in sepsis. DESIGN: Observational human pilot study-prospective controlled animal study. SETTING: University hospital and research laboratory...
October 31, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/29090412/improved-debulking-of-peritoneal-tumor-implants-by-near-infrared-fluorescent-nanobody-image-guidance-in-an-experimental-mouse-model
#19
Pieterjan Debie, Marian Vanhoeij, Natalie Poortmans, Janik Puttemans, Kris Gillis, Nick Devoogdt, Tony Lahoutte, Sophie Hernot
PURPOSE: Debulking followed by combination chemotherapy is currently regarded as the most effective treatment for advanced ovarian cancer. Prognosis depends drastically on the degree of debulking. Accordingly, near-infrared (NIR) fluorescence imaging has been proposed to revolutionize cancer surgery by acting as a sensitive, specific, and real-time tool enabling visualization of cancer lesions. We have previously developed a NIR-labeled nanobody that allows fast, specific, and high-contrast imaging of HER2-positive tumors...
October 31, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29061039/quantitatively-predictable-control-of-cellular-protein-levels-through-proteasomal-degradation
#20
Wenting Zhao, Lara Pferdehirt, Laura Segatori
Protein function is typically studied and engineered by modulating protein levels within the complex cellular environment. To achieve fast, targeted, and predictable control of cellular protein levels without genetic manipulation of the target, we developed a technology for post-translational depletion based on a bifunctional molecule (NanoDeg) consisting of the antigen-binding fragment from the Camelidae species heavy-chain antibody (nanobody) fused to a degron signal that mediates degradation through the proteasome...
November 7, 2017: ACS Synthetic Biology
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