Publications by authors named "Tom Z Yuan"

Article Synopsis
  • - SARS-CoV-2 is continuously evolving, posing challenges to existing vaccines and treatments, which has led to the development of a new pipeline for creating effective VHH antibodies and bispecifics to neutralize various virus variants.
  • - High-affinity VHH antibodies were discovered through targeted phage library techniques, resulting in a bispecific construct that effectively combats multiple SARS-CoV-2 variants, showing enhanced resistance to antigenic escape.
  • - The new tetravalent bispecific platform enables speedy development and production of antibodies, providing flexible and potent responses to emerging variants, making it a promising method for ongoing viral management.
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  • Scientists are finding new ways to help immunotherapy work better by targeting a protein called A2A receptor (A2AR) that can make cancer stronger.
  • They discovered a special antibody called TB206-001 that can block A2AR and potentially help the body's immune system fight tumors more effectively.
  • TB206-001 has shown strong results in lab tests and could be used in future cancer treatments that combine different therapies for better results.
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Unlabelled: Congenital hyperinsulinism (HI) is a genetic disorder in which pancreatic β-cell insulin secretion is excessive and results in hypoglycemia that, without treatment, can cause brain damage or death. Most patients with loss-of-function mutations in ABCC8 and KCNJ11, the genes encoding the β-cell ATP-sensitive potassium channel (KATP), are unresponsive to diazoxide, the only U.S.

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The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike.

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Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries.

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Antibody-based therapeutics and vaccines are essential to combat COVID-19 morbidity and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple mutations in SARS-CoV-2 that could impair antibody defenses propagated in human-to-human transmission and spillover or spillback events between humans and animals. To develop prevention and therapeutic strategies, we formed an international consortium to map the epitope landscape on the SARS-CoV-2 spike protein, defining and structurally illustrating seven receptor binding domain (RBD)–directed antibody communities with distinct footprints and competition profiles.

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Article Synopsis
  • The Wnt signaling pathway plays a critical role in regulating bone mass in both humans and rodent models, and researchers have developed a new antibody-based platform to create effective Wnt mimetics.
  • These engineered bi-specific Wnt mimetics target specific proteins to enhance bone growth in mice, demonstrating significant improvements in various bone-related conditions like osteoporosis and fractures.
  • Combining these Wnt mimetics with existing treatments like bisphosphonates enhances bone accrual, suggesting their potential for treating conditions related to low bone mineral density.
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Background: Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences.

Methods And Results: A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature.

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G protein-coupled receptors (GPCRs) are a group of seven-transmembrane receptor proteins that have proven to be successful drug targets. Antibodies are becoming an increasingly promising modality to target these receptors due to their unique properties, such as exquisite specificity, long half-life, and fewer side effects, and their improved pharmacokinetic and pharmacodynamic profiles compared to peptides and small molecules, which results from their more favorable biodistribution. To date, there are only two US Food and Drug Administration-approved GPCR antibody drugs, namely erenumab and mogamulizumab, and this highlights the challenges encountered in identifying functional antibodies against GPCRs.

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Recombinant protein overexpression of large proteins in bacteria often results in insoluble and misfolded proteins directed to inclusion bodies. We report the application of shear stress in micrometer-wide, thin fluid films to refold boiled hen egg white lysozyme, recombinant hen egg white lysozyme, and recombinant caveolin-1. Furthermore, the approach allowed refolding of a much larger protein, cAMP-dependent protein kinase A (PKA).

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Phage display offers a powerful approach to engineer protein affinity. A naturally occurring analog to phage display, the Bordetella bronchiseptica bacteriophage (BP) employs a highly variable protein termed the major tropism determinant (Mtd) to recognize its dynamic host. Propagation of BP provides a self-made phage library (SMPL) with vast numbers of phage particles, each displaying a single Mtd variant.

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Phage display libraries are widely used as tools for identifying, dissecting and optimizing ligands. Development of a simple method to access greater library diversities could expedite and expand the technique. This paper reports progress toward harnessing the naturally occurring diversity generating retroelement used by Bordetella bronchiseptica bacteriophage to alter its tail-fiber protein.

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