A5102853150- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Protein purification and stability
- Bacteriophages and microbial interactions
- COVID-19 Clinical Research Studies
- Biosimilars and Bioanalytical Methods
- Extracellular vesicles in disease
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Bacterial biofilms and quorum sensing
- Receptor Mechanisms and Signaling
- SARS-CoV-2 detection and testing
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Chemical Synthesis and Analysis
- Bacillus and Francisella bacterial research
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
BioSurfaces (United States)
2021-2024
University of Michigan–Ann Arbor
2021-2024
AstraZeneca (United States)
2024
Michigan United
2022
University of Maryland, College Park
2014-2020
Therapeutic antibody development requires selection and engineering of molecules with high affinity other drug-like biophysical properties. Co-optimization multiple properties remains a difficult time-consuming process that impedes drug development. Here we evaluate the use machine learning to simplify co-optimization for clinical-stage (emibetuzumab) displays levels both on-target (antigen) off-target (non-specific) binding. We mutate sites in complementarity-determining regions, sort...
Abstract The COVID‐19 pandemic continues to be a severe threat human health, especially due current and emerging SARS‐CoV‐2 variants with potential escape humoral immunity developed after vaccination or infection. development of broadly neutralizing antibodies that engage evolutionarily conserved epitopes on coronavirus spike proteins represents promising strategy improve therapy prophylaxis against thereof. Herein, facile multivalent engineering approach is employed achieve large...
SARS-CoV-2 variants with enhanced transmissibility represent a serious threat to global health. Here we report machine learning models that can predict the impact of receptor-binding domain (RBD) mutations on receptor (ACE2) affinity, which is linked infectivity, and escape from human serum antibodies, viral neutralization. Importantly, many known impacts RBD in current former Variants Concern affinity antibody as well novel sets strongly modulate both properties. Moreover, these reveal key...
Abstract Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies the rapid reliable isolation these antibodies, especially potent neutralizing critical toward improved COVID-19 response informed future to emergent infectious diseases. In this study, single B cell screening was used interrogate antibody repertoires...
We developed a hybrid synthetic circuit that co-opts the genetic regulation of native bacterial quorum sensing autoinducer-2 and imposes an extra external controller for maintaining tightly controlled gene expression. This dual-input was mathematically modeled and, by design, can be operated in three modes: constitutive mode enables consistent high levels expression; repressed which there is very little background inducible concentrations two signals (arabinose autoinducer-2) determine net...
Neutralizing monoclonal antibodies and nanobodies have shown promising results as potential therapeutic agents for COVID-19. Identifying such requires evaluating the neutralization activity of a large number lead molecules via biological assays, virus test (VNT). These assays are typically time-consuming demanding on-lab facilities. Here, we present rapid quantitative assay that evaluates neutralizing efficacy an antibody or nanobody within 1.5 h, does not require BSL-2 facilities, consumes...
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...
Summary Agonist antibodies that activate cellular receptors are being pursued for therapeutic applications ranging from neurodegenerative diseases to cancer. For the tumor necrosis factor (TNF) receptor superfamily, higher-order clustering of three or more is key their potent activation. This can be achieved using recognize two unique epitopes on same and mediate superclustering. However, identifying compatible pairs generate biepitopic (also known as biparatopic antibodies) activating TNF...