A5089296826- Viral Infectious Diseases and Gene Expression in Insects
- Monoclonal and Polyclonal Antibodies Research
- Protein purification and stability
- Microbial Metabolic Engineering and Bioproduction
- Glycosylation and Glycoproteins Research
- Gene Regulatory Network Analysis
- CRISPR and Genetic Engineering
- Advanced Control Systems Optimization
- SARS-CoV-2 and COVID-19 Research
- thermodynamics and calorimetric analyses
- Probabilistic and Robust Engineering Design
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- 3D Printing in Biomedical Research
- Transgenic Plants and Applications
- Bioinformatics and Genomic Networks
- Vaccine Coverage and Hesitancy
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Advanced Multi-Objective Optimization Algorithms
- Biofuel production and bioconversion
- Carbohydrate Chemistry and Synthesis
- Mesenchymal stem cell research
- Endoplasmic Reticulum Stress and Disease
Imperial College London
2016-2025
Imperial Valley College
2017
Transnational Press London
2017
John Wiley & Sons (United States)
2015-2017
Bioengineering Center
2015-2017
National Center for Genetic Engineering and Biotechnology
2015-2017
Hudson Institute
2017
Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in biopharmaceutical industry. Amino acid and glucose consumption, growth, metabolism, antibody titer, N-glycosylation patterns are always major concerns during upstream optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight obtaining higher immunoglobulin G (IgG) titer better controlling glycosylation-related product quality. In this...
Abstract Monoclonal antibodies (mAbs) are one of the most important products biopharmaceutical industry. Their therapeutic efficacy depends on post‐translational process glycosylation, which is influenced by manufacturing conditions. Herein, we present a dynamic mathematical model for mAb glycosylation that considers cisternal maturation approximating Golgi apparatus to plug flow reactor and including recycling Golgi‐resident proteins (glycosylation enzymes transport [TPs]). The reaction...
To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA for demand associated with a global vaccination campaign. Production process performance is assessed three messenger (mRNA) and one self-amplifying (saRNA) vaccines, all currently under clinical development, well hypothetical next-generation saRNA vaccine. The impact key design operation uncertainties on production was assessed. vaccine...
ABSTRACT The application of mild hypothermic conditions to cell culture is a routine industrial practice used improve recombinant protein production. However, thorough understanding the regulation dynamic cellular processes at lower temperatures necessary enhance bioprocess design and optimization. In this study, we investigated impact hypothermia on glycosylation. Chinese hamster ovary (CHO) cells expressing monoclonal antibody (mAb) were cultured 36.5°C with temperature shift 32°C during...
Abstract Overcoming pandemics, such as the current Covid‐19 outbreak, requires manufacture of several billion doses vaccines within months. This is an extremely challenging task given constraints in small‐scale manufacturing for clinical trials, testing timelines involving multiple phases and large‐scale drug substance product manufacturing. To tackle these challenges, regulatory processes are fast‐tracked, rapid‐response platform technologies used. Here, we evaluate progress, challenges...
Kinetic models offer incomparable insight on cellular mechanisms controlling protein glycosylation. However, their ability to reproduce site-specific glycoform distributions depends accurate estimation of a large number protein-specific kinetic parameters and prior knowledge enzyme transport levels in the Golgi membrane. Herein we propose an artificial neural network (ANN) for glycosylation apply this four recombinant glycoproteins produced Chinese hamster ovary (CHO) cells, two monoclonal...
Abstract Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead outbreaks. We the first apply Quality by Design (QbD) framework enhance rapid-response against known future pathogens. This QbD aims support development consistent safe efficacious integrating a novel qualitative methodology...
Abstract Glycosylation is a critical post-translational protein modification that affects folding, half-life and functionality. non-templated heterogeneous process because of the promiscuity enzymes involved. We describe platform for sequential glycosylation reactions tailored sugar structures (SUGAR-TARGET) allows bespoke, controlled N-linked in vitro enabled by immobilized produced with one-step immobilization/purification method. reconstruct reaction cascade mimicking pathway where...
Glycoproteins represent the largest group of growing number biologically-derived medicines. The associated glycan structures and their distribution are known to have a large impact on pharmacokinetics. A modelling framework was developed provide link from extracellular environment its effect intracellular metabolites glycans constant region an antibody product. main focus this work is mechanistic in silico reconstruction nucleotide sugar donor (NSD) metabolic network by means 34 species mass...
Abstract Exerting control over the glycan moieties of antibody therapeutics is highly desirable from a product safety and batch‐to‐batch consistency perspective. Strategies to improve productivity may compromise quality, while interventions for improving glycoform distribution can adversely affect cell growth productivity. Process design therefore needs consider trade‐off between preserving cellular health enhancing quality. In this work, we present modeling platform that quantifies impact...
The addition of nutrients and accumulation metabolites in a fed-batch culture Chinese hamster ovary (CHO) cells leads to an increase extracellular osmolality late stage culture. Herein, we explore the effect on CHO cell growth, specific monoclonal antibody (mAb) productivity glycosylation achieved with NaCl or supplementation commercial feed. Although both methods lead productivity, they have different effects growth production. Osmolality modulation using up 470 mOsm kg−1 had consistently...
In this study, omics-based analysis tools were used to explore the effect of glucose starvation and culture duration on monoclonal antibody (mAb) production in fed-batch CHO cell gain better insight into how these parameters can be controlled ensure optimal mAb productivity quality. Titer N-glycosylation mAbs, as well proteomic signature metabolic status cells assessed. We found that impact titer mAbs was dependent degree during early stationary phase culture. Higher reduced intracellular...
Many high-value added recombinant proteins, such as therapeutic glycoproteins, are produced using mammalian cell cultures. In order to optimize the productivity of these cultures it is important monitor cellular metabolism, for example utilization nutrients and accumulation metabolic waste products. One product interest lactic acid (lactate), overaccumulation which can decrease growth protein production. Current methods detection lactate limited in terms cost, sensitivity, robustness....