A5067922940- Monoclonal and Polyclonal Antibodies Research
- Bacterial biofilms and quorum sensing
- Glycosylation and Glycoproteins Research
- Fibroblast Growth Factor Research
- Protein purification and stability
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- Bacterial Genetics and Biotechnology
- bioluminescence and chemiluminescence research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Treatment and Pharmacology
- Mass Spectrometry Techniques and Applications
- vaccines and immunoinformatics approaches
- Glutathione Transferases and Polymorphisms
- Bacillus and Francisella bacterial research
- Bacteriophages and microbial interactions
- Bone health and treatments
- Photoreceptor and optogenetics research
- HER2/EGFR in Cancer Research
- Computational Drug Discovery Methods
- Medicinal plant effects and applications
- Cancer therapeutics and mechanisms
- Immunotherapy and Immune Responses
- Chemical Synthesis and Analysis
- Immune Response and Inflammation
AstraZeneca (United States)
2022-2025
Target (United States)
2022
University of California, Berkeley
2017-2020
University of Utah
2019-2020
Franklin & Marshall College
2015
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2–neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds the back left shoulder SARS-CoV-2 spike protein receptor binding domain prevents interaction with human angiotensin-converting enzyme receptor. potently neutralized broad...
Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field of biologics. In silico tools that can streamline process antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. High-quality structural information remains for process, but antibody-antigen structures often unavailable in docking methods still unreliable. this study, DeepAb, deep learning model predicting Fv structure directly...
Most previously authorized clinical antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have lost neutralizing activity to recent variants due rapid viral evolution. To mitigate such escape, we preemptively enhance AZD3152, an antibody for prophylaxis in immunocompromised individuals. Using deep mutational scanning (DMS) on the SARS-CoV-2 antigen, identify AZD3152 vulnerabilities at antigen positions F456 and D420. Through two iterations of computational design...
Bacteria colonize highly diverse and complex environments, from gastrointestinal tracts to soil plant surfaces. This colonization process is controlled in part by the intracellular signal cyclic di-GMP, which regulates bacterial motility biofilm formation. To interrogate di-GMP signaling networks, a variety of fluorescent biosensors for live cell imaging have been developed. However, need external illumination precludes use these tools bacteria their natural including deep tissues whole...
Second messenger signaling networks allow cells to sense and adapt changing environmental conditions. In bacteria, the nearly ubiquitous second molecule cyclic di-GMP coordinates diverse processes such as motility, biofilm formation, virulence. bacterial pathogens, these bacteria survive conditions that are experienced during infection of a mammalian host. While studies have examined effects levels on virulence in it has not been possible visualize real time stages host infection. Toward...
Abstract Background EVUSHELD was developed for the prevention and treatment of mild-to-moderate COVID-19 high-risk individuals. However, SARS-CoV-2 virus continues to evolve in presence natural- vaccine-acquired immunity, escaping previously authorized antibody therapies such as bebtelovimab EVUSHELD. AZD3152 selected neutralize all known variants concern is being provide immunocompromised individuals with continued protection against SARS-CoV-2. Methods Structural analyses were performed...
Highly concentrated antibody solutions are necessary for developing subcutaneous injections but often exhibit high viscosities, posing challenges in antibody-drug development, manufacturing, and administration. Previous computational models were only limited to a few dozen data points training, bottleneck generalizability. In this study, we measured the viscosity of panel 229 monoclonal antibodies (mAbs) develop predictive concentration mAb screening. We developed DeepViscosity, consisting...
Abstract Metastatic castration-resistant prostate cancer (mCRPC) continues to pose a significant clinical challenge and is associated with poor survival rates in patients who failed previous lines of androgen receptor axis-targeted therapies taxanes. Antibody drug conjugates (ADCs) provide novel approach traditional chemotherapy by targeting tumor-specific antigens deliver cytotoxic payloads while sparing normal tissue enhancing the therapeutic index. Herein, we describe preclinical...
Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities vivo remain highly challenging to study real time for individual cells. Here we show that flow cytometry can be performed complex media monitor single-cell population distributions dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF)...
The X-ray crystal structures of superfolder green fluorescent protein (sfGFP) containing the spectroscopic reporter unnatural amino acids (UAAs) 4-cyano-L-phenylalanine (pCNF) or 4-ethynyl-L-phenylalanine (pCCF) at two unique sites in have been determined. These UAAs were genetically incorporated into sfGFP a solvent-exposed loop region and/or partially buried site on β-barrel protein. these permit structural implications UAA incorporation for native structure to be assessed with high...
Abstract Over the last two decades, therapeutic antibodies have emerged as a rapidly expanding domain within field biologics. In silico tools that can streamline process of antibody discovery and optimization are critical to support pipeline is growing more numerous complex every year. this study, DeepAb, deep learning model for predicting Fv structure directly from sequence, was used design 200 potentially stabilized variants an anti-hen egg lysozyme (HEL) antibody. We sought determine...
T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability eradicate cancer cells. Nevertheless, the widespread utility classical CD3-targeted TCEs has been limited by narrow index (TI) linked systemic CD4+ activation and aberrant cytokine release. One attractive approach circumvent pan CD3+ cells reduce risk release syndrome is redirect specific subsets A promising strategy use peptide-major histocompatibility I bispecific antibodies...
To combat the COVID-19 pandemic, potential therapies have been developed and moved into clinical trials at an unprecedented pace. Some of most promising are neutralizing antibodies against SARS-CoV-2. In order to maximize therapeutic effectiveness such antibodies, Fc engineering modulate effector functions extend half-life is desirable. However, it critical that does not negatively impact developability properties as these play a key role in ensuring rapid development, successful...
Abstract Cyclic dinucleotides (CDNs) trigger the innate immune response in eukaryotic cells through stimulator of interferon genes (STING) signaling pathway. To decipher this complex cellular process, a better correlation between structure and downstream function is required. Herein, we report design immunostimulatory effect novel group c‐di‐GMP analogues. By employing an “atomic mutagenesis” strategy, changing one atom at time, class gradually modified CDNs was prepared. These analogues...
Bispecific antibodies represent an increasingly large fraction of biologics in therapeutic development due to their expanded scope functional capabilities. Asymmetric monovalent bispecific IgGs (bsIgGs) have the additional advantage maintaining a native antibody-like structure, which can provide favorable pharmacology and pharmacokinetic profiles. The production correctly assembled asymmetric bsIgGs, however, is complex engineering endeavor propensity for non-cognate heavy light chains...
ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTA Poxin on Both of Your Houses: Poxviruses Degrade the Immune Signal cGAMPAndrew B. DippelAndrew DippelDepartment Chemistry, University California, Berkeley, California 94720, United StatesDepartment Chemistry and Henry Eyring Center for Cell Genome Science, Utah, Salt Lake City, Utah 84112, StatesMore by Andrew Dippel Ming C. Hammond*Ming HammondDepartment States*E-mail: [email protected]. Tel: (801) 213-0892.More...
ABSTRACT Second messenger signaling networks allow cells to sense and adapt changing environmental conditions. In bacteria, the nearly ubiquitous second molecule cyclic di-GMP coordinates diverse processes such as motility, biofilm formation, virulence. bacterial pathogens, these bacteria survive environment conditions that are experienced during infection of a mammalian host. While studies have examined effects levels on virulence in it has previously not been possible visualize real time...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein is of interest for the development vaccines and therapeutics against COVID-19. Vaccines are designed to raise an immune response protein. Other therapies attempt block interaction mammalian cells. Therefore, itself specific interacting regions reagents required by industry enable advancement medicines combat SARS-CoV-2. Early production methods SARS-CoV-2 receptor binding domain (RBD) were labor intensive with...