A5070919006- RNA Interference and Gene Delivery
- Protein purification and stability
- Microfluidic and Capillary Electrophoresis Applications
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Analytical Chemistry and Chromatography
- Viral Infectious Diseases and Gene Expression in Insects
- SARS-CoV-2 and COVID-19 Research
- Herpesvirus Infections and Treatments
- Immunotherapy and Immune Responses
- Biosensors and Analytical Detection
- Clostridium difficile and Clostridium perfringens research
- Advanced biosensing and bioanalysis techniques
- Microfluidic and Bio-sensing Technologies
- Pneumonia and Respiratory Infections
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Resistance in Staphylococcus
- PARP inhibition in cancer therapy
- Viral Infections and Outbreaks Research
- Advanced Biosensing Techniques and Applications
- Bacterial Infections and Vaccines
- CAR-T cell therapy research
- Toxoplasma gondii Research Studies
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013-2024
High Throughput Biology (United States)
2024
United States Military Academy
2014-2022
Institut de Recherche Vaccinale
2015
Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection, and developing a prophylactic vaccine high priority to public health. We recently reported replication-defective human with restored pentameric complex glycoprotein H (gH)/gL/pUL128-131 for prevention HCMV infection. While quantity vaccine-induced antibody responses can be measured in neutralization assay, assessing quality such responses, including ability antibodies cross-neutralize field strains HCMV, remains...
Many CE-based technologies such as imaged capillary IEF, CE-SDS, CZE, and MEKC are well established for analyzing proteins, viruses, or other biomolecules polysaccharides. For example, isoelectric focusing (charge-based protein separation) CE-SDS (size-based standard replacement methods in biopharmaceutical industries tedious labor intensive IEF SDS-PAGE methods, respectively. Another important analytical tool characterization is a Western blot, where after size-based separation the proteins...
Messenger RNA (mRNA) vaccines have emerged as a flexible platform for vaccine development. The evolution of lipid nanoparticles effective delivery vehicles modified mRNA encoding antigens was demonstrated by the response to COVID-19 pandemic. ability rapidly develop SARS-CoV-2 from spike protein genome, and then manufacture multibillions doses per year an extraordinary achievement milestone. Further development application this additional pathogens is clearly interest. This comes with...
Congenital infection of human cytomegalovirus (HCMV) is one the leading causes nongenetic birth defects, and development a prophylactic vaccine against HCMV high priority for public health. The gH/gL/pUL128–131 pentameric complex mediates entry into endothelial epithelial cells, it major target neutralizing antibody responses. To better understand mechanism by which antibodies interact with epitopes resulting in viral neutralization, we expressed purified soluble gH/gL from Chinese hamster...
Messenger RNA (mRNA)-based vaccines are advantageous because they can be relatively quicker and more cost efficient to manufacture compared other traditional vaccine products. Lipid nanoparticles have three common purposes: delivery, self-adjuvanting properties, mRNA protection. Faster development requires an fast assay monitor purity integrity. Microchip CE is known a robust technology that capable of rapid separation. Here, we describe the optimization integrity for mRNA-based encapsulated...
The development of mRNA vaccines has increased rapidly since the COVID-19 pandemic. As one critical attributes, understanding lipid nanoparticle (LNP) stability is in vaccine product development. However, correlation between LNPs’ physiochemical characteristics and their potency still remains unclear. lack regulatory guidance on specifications for LNPs also partially due to this underexplored relationship. In study, we performed a three-month study heat-stressed LNP samples. samples were...
Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates common. One reason for this that hypervirulent C. strains often have a binary toxin termed the toxin, in addition to enterotoxins TsdA TsdB. The has an enzymatic component, CDTa, pore-forming or delivery subunit CDTb. CDTb was characterized here using combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, other biophysical methods. In absence...
Abstract For many years, lipid nanoparticles (LNPs) have been used as delivery vehicles for various payloads (especially oligonucleotides and mRNA), finding numerous applications in drug vaccine development. LNP stability bilayer fluidity are determined by the identities amounts of lipids employed formulation efficacy is large part composition which usually contains a cationic lipid, PEG‐lipid conjugate, cholesterol, zwitterionic helper phospholipid. Analytical methods developed...
Lipid nanoparticles (LNPs) have been employed for drug delivery in small molecules, siRNA, mRNA, and pDNA both therapeutics vaccines. Characterization of LNPs is challenging because they are heterogeneous mixtures large complex particles. Many tools particle size characterization, such as dynamic static light scattering, applied well morphology analysis using electron microscopy. CE has the characterization many different particles liposomes, polymer, viruses. However, there limited efforts...
The employment of ethylenediaminetetraacetic acid (EDTA) across several fields in chemistry and biology has required the creation a high number quantitative assays. Nonetheless, determination trace EDTA, especially biologics vaccines, remains challenging. Herein, we introduce an automated high-throughput approach based on EDTA esterification 96-well plates using boron trifluoride-methanol combined with rapid analysis by ultra-high-performance liquid chromatography–triple quadrupole tandem...
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases immunocompromised patients. HCMV has large genome with enormous coding potential; its viral particles are equipped complicated glycoprotein complexes infect wide range of human cells. Although multiple host cellular receptors interacting glycoproteins have been reported, the mechanism infection remains mystery. Here we report identification adipocyte plasma...
Ebolavirus (EBOV) entry to host cells requires membrane-associated glycoprotein (GP). A recombinant vesicular stomatitis virus vector carrying Zaire Ebola (rVSV-ZEBOV) was developed as a vaccine against ebolaviruses. The VSV gene deleted (rVSVΔG) and ZEBOV (GP) inserted into the open reading frame (ORF) resulting in live, replication-competent (rVSVΔG-ZEBOV-GP). Automated capillary westerns were used characterize rVSVΔG-ZEBOV-GP (ERVEBO®) manufacturing process with regards structure...
Both poly and mono ADP-ribosylation are common posttranslational protein modifications. For example, is involved in DNA repair mechanisms through the (ADP-ribose) polymerase (PARP) family of enzymes. While has been known to trigger cell death exhibited by many bacterial toxins. Because wide role ADP-ribosylation, detection analysis very important for further understanding PARP enzymes molecular leading toxicity presence Here, we describe a novel technique utilizing CE-based Western...
V937 is an oncolytic virus immunotherapy clinical drug candidate consisting of a proprietary formulation Coxsackievirus A21 (CVA21). specifically binds to and lyses cells with over-expressed ICAM-1 receptors in range tumor cell types currently phase I II trials. Infectious particles consist ∼30 nm icosahedral capsid assembled from four structural viral proteins that encapsidate RNA genome. Rapid robust analytical methods quantify characterize CVA21 are important support the process...
Dengue fever has remained a continuing global medical threat that impacts half of the world’s population. Developing highly effective dengue vaccine, with live-attenuated tetravalent vaccines as leading candidates, remains essential in preventing this disease. For development live virus (LVVs), potency measurements play vital role quantifying active components vaccine drug substance well product during various stages research, development, and post-licensure evaluations. Traditional...
The rise of mRNA as a novel vaccination strategy presents new opportunities to confront global disease. Double-stranded RNA (dsRNA) is an impurity byproduct the in vitro transcription reaction used manufacture that may affect potency and safety vaccine patients. Careful quantitation dsRNA during manufacturing critical ensure residual minimized purified drug substances. In this work, we describe development implementation sandwich Enzyme-Linked Immunosorbent Assay (ELISA) quantitate nanogram...
High Throughput Screening is crucial in pharmaceutical companies for efficient testing drug discovery and development. Our Vaccines Analytical Research Development Department (V-AR&D) extensively uses Robotic Liquid Handlers their Analytics (HTA) group assay development sample screening. However, these instruments are expensive require extensive training. Opentrons' OT-2 liquid handler offers a more affordable option (< $10,000) with Python programming language open-source flexibility,...