Publications

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reduction of charge variants by cho cell culture process optimization.over the past decade, global interest in the development of therapeutic monoclonal antibodies (mabs) has risen rapidly. as therapeutic agents, antibodies have shown marked efficacy in combatting a range of cancers and immune diseases with high target specificity and low toxicity (carla lucia et al. in plos one 6:e24071, 2011; donaghy in mabs 8:659-671, 2016; nasiri et al. in j cell physiol 9:6441-6457, 2018; teo et al. in cancer immunol immunother 61:2295-2309, 2012). recent advances in cell cul ...202032236800
influence of polymer charge on the localization and dark- and photo-induced toxicity of a potential type i photosensitizer in cancer cell models.a current trend within photo-dynamic therapy (pdt) is the development of molecular systems targeting hypoxic tumors. thus, type i pdt sensitizers could here overcome traditional type ii molecular systems that rely on the photo-initiated production of toxic singlet oxygen. here, we investigate the cell localization properties and toxicity of two polymeric anthracene-based fluorescent probes (neutral ant-phea and cationic ant-pim). the cell death and dna damage of chinese hamster ovary cancer cell ...202032138280
enhancement of sialylation in rigg in glyco-engineered chinese hamster ovary cells.since about 70% of commercial biopharmaceutical products have been produced in chinese hamster ovary (cho) cells, this cell line is undeniably a workhorse for biopharmaceuticals production. meanwhile, sialic acid terminals were reported to affect anti-inflammatory activity, antibody-dependent cellular cytotoxicity efficacy of igg antibodies. taking these findings together, we aimed to establish cho cell lines that highly produce sialic acid terminals by overexpressing two n-acetylneuraminic acid ...202032125558
a role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen fel d 4.lipocalins, small extracellular hydrophobic molecule carriers, can be internalized by a variety of different cells. however, to date receptors have only been identified for human lipocalins. here, we specifically investigated uptake mechanisms for lipocalins ß-lactoglobulin and fel d 4 in hela and chinese hamster ovary (cho) cells. we provide evidence that cell surface heparan sulphate proteoglycan is essential for internalization of these lipocalins. in hela cells, lipocalin uptake was inhibite ...202032229688
ascorbic acid 2-glucoside pretreatment protects cells from ionizing radiation, uvc, and short wavelength of uvb.ascorbic acid 2-glucoside (aa2g), glucosylated ascorbic acid (aa), has superior properties for bioavailability and stability compared to aa. although aa2g has shown radioprotective properties similar to aa, effects for uv light, especially uvc and uvb, are not studied. aa2g was tested for cytotoxicity and protective effects against ionizing radiation, uvc, and broadband and narrowband uvb in chinese hamster ovary (cho) cells and compared to aa and dimethyl sulfoxide (dmso). pretreatment with dms ...202032106443
a proteomic approach towards understanding crypoprotective action of me2so on the cho cell proteome.chinese hamster ovary (cho) cell lines are the most widely used in vitro cells for research and production of recombinant proteins such as rhgh, tpa, and erythropoietin. we aimed to investigate changes in protein profiles after cryopreservation using 2d-dige maldi-tof ms and network pathway analysis. the proteome changes that occur in cho cells between freshly prepared cells and cryopreserved cells with and without me2so were compared to determine the key proteins and pathways altered during rec ...202032259523
comparison of a novel homogeneous cyclic amp assay and a luciferase assay for measuring stimulating thyrotropin-receptor autoantibodies.stimulating thyrotropin-receptor antibodies (tsab) cause graves' disease (gd). we tested a novel homogeneous fluorescent 3',5' cyclic adenine monophosphate (camp) assay for the detection of tsab in a bioassay.202032257955
antiarrhythmic mechanisms of chinese herbal medicine dingji fumai decoction.dingji fumai decoction (dfd) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. however, its cellular electrophysiological mechanism is unknown.202032256664
screening of new cell cycle suppressive compounds from marine-derived microorganisms in chinese hamster ovary cells.monoclonal antibodies (mabs) are active pharmaceutical ingredients in antibody drugs, produced mainly using recombinant chinese hamster ovary (cho) cells. the regulation of recombinant cho cell proliferation can improve the productivity of heterologous proteins. chemical compound approaches for cell cycle regulation have the advantages of simplicity and ease of use in industrial processes. however, cho cells have genetic and phenotypic diversity, and the effects of such compounds might depend on ...202032253091
development of magoh protein-overexpressing hek cells for optimized therapeutic protein production.in the pharmaceutical industry, the need for high levels of protein expression in mammalian cells has prompted the search for new strategies, including technologies to obtain cells with improved mechanisms that enhance its transcriptional activity, folding, or protein secretion. chinese hamster ovary (cho) cells are by far the most used host cell for therapeutic protein expression. however, these cells produce specific glycans that are not present in human cells and therefore potentially immunog ...202032249976
synthesis and biological evaluation of antibody drug conjugates based on an antibody expression system: conamax.antibody production for adcs (or in general) is commonly performed by cho-based platforms and limited by volumetric productivity, expensive downstream purification, and extended optimization timelines. the conamax platform is a novel microbial-based protein production and secretion system. a suite of synthetic biology tools have enabled high volumetric productivity (>1 g/l/d) and glycoengineering to produce simple and consistent human-like post-translational modifications. conamax can be enginee ...202032280859
safety evaluation of water extract of gastrodia elata blume: genotoxicity and 28-day oral toxicity studies.water extract of gastrodia elata blume (wge) has great potential as an anti-depressant and could be developed as a functional food. this study aims to assess the safety of wge using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. results from a bacterial reverse mutation assay (ames test) using five salmonella typhimurium strains (ta98, ta100, ta102, ta1535, and ta1537) with or without metabolic activation (s9 system) showed that wge did not induce mutagenicity. nor di ...202032278877
changes of resurgent na+ currents in the nav1.4 channel resulting from an scn4a mutation contributing to sodium channel myotonia.myotonia congenita (mc) is a rare disorder characterized by stiffness and weakness of the limb and trunk muscles. mutations in the scn4a gene encoding the alpha-subunit of the voltage-gated sodium channel nav1.4 have been reported to be responsible for sodium channel myotonia (scm). the nav1.4 channel is expressed in skeletal muscles, and its related channelopathies affect skeletal muscle excitability, which can manifest as scm, paramyotonia and periodic paralysis. in this study, the missense mu ...202032276507
assessing additivity of cytotoxicity associated with disinfection byproducts in potable reuse and conventional drinking waters.recent studies used the sum of the measured concentrations of individual disinfection byproducts (dbps) weighted by their chinese hamster ovary (cho) cell cytotoxicity lc50 values to estimate the dbp-associated cytotoxicity of disinfected waters. this approach assumed that cytotoxicity was additive rather than synergistic or antagonistic. in this study, we evaluated whether this assumption was valid for mixtures containing dbps at the concentration ratios measured in authentic disinfected waters ...202032275830
cell-free protein synthesis: a promising option for future drug development.proteins are the main source of drug targets and some of them possess therapeutic potential themselves. among them, membrane proteins constitute approximately 50% of the major drug targets. in the drug discovery pipeline, rapid methods for producing different classes of proteins in a simple manner with high quality are important for structural and functional analysis. cell-free systems are emerging as an attractive alternative for the production of proteins due to their flexible nature without a ...202032198631
spike protein recognition of mammalian ace2 predicts the host range and an optimized ace2 for sars-cov-2 infection.sars-cov-2 causes the recent global covid-19 public health emergency. ace2 is the receptor for both sars-cov-2 and sars-cov. to predict the potential host range of sars-cov-2, we analyzed the key residues of ace2 for recognizing s protein. we found that most of the selected mammals including pets (dog and cat), pangolin and circetidae mammals remained the most of key residues for association with s protein from sars-cov and sars-cov-2. the interaction interface between cat/dog/pangolin/chinese h ...202032201080
improved identification of host cell proteins in a protein biopharmaceutical by lc-ms/ms using the proteominer™ enrichment kit.host cell proteins (hcps) in biotherapeutics can be identified by the use of enzymatic digestion and lc-ms/ms analysis. however, the major challenge is that hcps are often present at very low levels in relation to the protein drug (low ppm-levels). in this study, the proteominer™ enrichment kit (bio-rad) was evaluated as a strategy to enable identification of hcps by lc-ms/ms by enrichment of low-abundant hcps and a simultaneous depletion of the high-abundant product protein. a recombinant prote ...202032229402
defects in galactose metabolism and glycoconjugate biosynthesis in a udp-glucose pyrophosphorylase-deficient cell line are reversed by adding galactose to the growth medium.udp-glucose (udp-glc) is synthesized by ugp2-encoded udp-glc pyrophosphorylase (ugp) and is required for glycoconjugate biosynthesis and galactose metabolism because it is a uridyl donor for galactose-1-p (gal1p) uridyltransferase. chinese hamster lung fibroblasts harboring a hypomrphic ugp(g116d) variant display reduced udp-glc levels and cannot grow if galactose is the sole carbon source. here, these cells were cultivated with glucose in either the absence or presence of galactose in order to ...202032188137
circulating ficolin-2 and ficolin-3 form heterocomplexes.the complement system constitutes an important part of the innate immune system. the collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. during previous experiments with ficolin-2 and ficolin-3, we have observed that the molecules may interact. we therefore hypothesized the existence of stable ficolin-2/-3 heterocomplexes. we could demonstrate ficolin-2/-3 heterocomplexes in normal human serum and plasma by elisa ...202032094208
lycopene alleviates oxidative stress via the pi3k/akt/nrf2pathway in a cell model of alzheimer's disease.oxidative stress (os) plays an important role in neurodegenerative diseases such as alzheimer's disease (ad). lycopene is a pigment with potent antioxidant and anti-tumor effects. however, its potential role in central nervous system is not well-defined. the aim of this study was to investigate the effect of lycopene on the cell model of ad and determine its underlying mechanisms.202032551202
cytotoxicity and mutagenicity of narrowband uvb to mammalian cells.phototherapy using narrowband ultraviolet-b (nb-uvb) has been shown to be more effective than conventional broadband uvb (bb-uvb) in treating a variety of skin diseases. to assess the difference in carcinogenic potential between nb-uvb and bb-uvb, we investigated the cytotoxicity via colony formation assay, genotoxicity via sister chromatid exchange (sce) assay, mutagenicity via hypoxanthine phosphoribosyltransferase (hprt) mutation assay, as well as cyclobutane pyrimidine dimer (cpd) formation ...202032545288
the p.p888l sap97 polymorphism increases the transient outward current (ito,f) and abbreviates the action potential duration and the qt interval.synapse-associated protein 97 (sap97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates na+ and k+ channels. here we compared the electrophysiological effects of native (wt) and p.p888l sap97, a common polymorphism. currents were recorded in cardiomyocytes from mice trans-expressing human wt or p.p888l sap97 and in chinese hamster ovary (cho)-transfected cells. the duration of the action potentials and the qt interval were significantly shorter in p.p888l-sap97 ...202032612162
functional pasta consumption in healthy volunteers modulates abcg1-mediated cholesterol efflux capacity of hdl.prevention of cardiovascular (cv) disease is considered a central issue in public health and great attention is payed to nutritional approaches, including consumption of functional foods to reduce cv risk in individuals without indications for anti-atherosclerotic drugs. cholesterol efflux capacity (cec) is an important anti-atherogenic property of hdl and a marker of cv risk. we evaluated the effect of a daily consumption of an innovative whole-wheat synbiotic pasta, compared to a control whole ...202032605885
evaluation of osteogenic/cementogenic modulating potential of pai-1 transfected media for stem cells.in vitro evaluation of the effects of plasminogen activator inhibitor-1 (pai-1) transfected-conditioned media (p-cm) on the differentiation of human periodontal ligament stem cells (hpdlscs) and human periapical follicular stem cells (hpafscs).202032603295
design, construction, and expression of recombinant human interferon beta gene in cho-s cell line using ebv-based expression system.codon optimization has been considered as a powerful strategy to increase the expression level of protein therapeutics in mammalian cells. as an empirical approach to study the effects of the codon usage and gc content on heterologous gene expression in suspension adapted chinese hamster ovary (cho-s) cells, we redesigned the recombinant human interferon beta (rhifn- β) gene based on the codon preference of the cho cell in a way to increase the gc content in the third position of each codon.202032582354
analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro.background tumor cells can die via immunogenic cell death pathway, in which damage-associated molecular pattern molecules (damps) are released from the cells. these molecules activate cells involved in the immune response. both innate and adaptive immune response can be activated, causing a destruction of the remaining infected cells. activation of immune response is also an important component of tumor treatment with electrochemotherapy (ect) and irreversible electroporation (ire). we thus expl ...202032726295
enabling speed to clinic for monoclonal antibody programs using a pool of clones for ind-enabling toxicity studies.the importance of speed to clinic for medicines that may address unmet medical needs puts pressure on product development timelines. historically, both toxicology and first-in-human clinical materials are generated using the same clonal-derived cells to ensure safety and minimize any development risks. however, cell line development with single cell cloning is time consuming, and aggravated by the time needed to screen for a lead clone based on cell line stability and manufacturability. in order ...202032449878
detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and ipsc-derived neurons.good's buffers are commonly used for cell culture and, although developed to have minimal to no biological impact, they cause alterations in cellular processes such as autophagy and lysosomal enzyme activity. using chinese hamster ovary cells and induced pluripotent stem cell-derived neurons, this study explores the effect of zwitterionic buffers, specifically hepes, on lysosomal volume and ca2+ levels. certain zwitterionic buffers lead to lysosomal expansion and reduced lysosomal ca2+. care sho ...202032490352
harnessing the potential of artificial neural networks for predicting protein glycosylation.kinetic models offer incomparable insight on cellular mechanisms controlling protein glycosylation. however, their ability to reproduce site-specific glycoform distributions depends on accurate estimation of a large number of protein-specific kinetic parameters and prior knowledge of enzyme and transport protein levels in the golgi membrane. herein we propose an artificial neural network (ann) for protein glycosylation and apply this to four recombinant glycoproteins produced in chinese hamster ...202032489858
excito-repellency and biological safety of β-caryophyllene oxide against aedes albopictus and anopheles dirus (diptera: culicidae).the activity of β-caryophyllene oxide as either a contact or noncontact repellent was evaluated against two laboratory strains (aedes albopictus and anopheles dirus) using an excito-repellency test system. n, n-diethyl-3-methylbenzamide (deet) was used as a standard reference baseline for comparative purposes. β-caryophyllene oxide and deet were tested at concentrations of 0.1, 0.25, 0.5 and 1.0% (v/v). in addition, the phototoxic and genotoxic effects of β-caryophyllene oxide were investigated ...202032485168
antimicrobial activity, toxicity and accumulated hard-tissue debris (ahtd) removal efficacy of several chelating agents.to evaluate the antimicrobial, toxicity and cleaning effectiveness of ethylenediaminetetraacetic acid (edta) and maleic acid (ma) alone and combined with cetrimide (ctr).202032344451
a doubly auxotrophic cho-k1 cell line for the production of recombinant monoclonal antibodies.chinese hamster ovary (cho) cells are the most widely used mammalian hosts for recombinant protein production due to their hardiness, ease of transfection, and production of glycan structures similar to those in natural human monoclonal antibodies. to enhance the usefulness of cho-k1 cells we developed a new selection system based on double auxotrophy. we used crispr-cas9 to knockout the genes that encode the bifunctional enzymes catalyzing the last two steps in the de novo synthesis of pyrimidi ...202032346859
short communication: the essential role of n-glycosylation in the transport activity of bovine peptide transporter 2.bovine peptide transporter 2 (bpept2), which mediates the absorption of di- and tripeptides in the bovine mammary gland, was predicted to contain multiple putative n-glycosylation sites of asparagine residues. n-linked glycosylation is proven to be essential for the folding, stability, localization, and substrate binding of nutrient transporters and could therefore potentially have an essential role in the function of bpept2. this study investigated the effect of mutagenesis of n-glycosylation s ...202032331895
enzyme capacity-based genome scale modelling of cho cells.chinese hamster ovary (cho) cells are most prevalently used for producing recombinant therapeutics in biomanufacturing. recently, more rational and systems approaches have been increasingly exploited to identify key metabolic bottlenecks and engineering targets for cell line engineering and process development based on the cho genome-scale metabolic model which mechanistically characterizes cell culture behaviours. however, it is still challenging to quantify plausible intracellular fluxes and d ...202032330653
biological filtering and substrate promiscuity prediction for annotating untargeted metabolomics.mass spectrometry coupled with chromatography separation techniques provides a powerful platform for untargeted metabolomics. determining the chemical identities of detected compounds however remains a major challenge. here, we present a novel computational workflow, termed extended metabolic model filtering (emmf), that aims to engineer a candidate set, a listing of putative chemical identities to be used during annotation, through an extended metabolic model (emm). an emm includes not only can ...202032326153
genotoxicity of micro- and nano-particles of kaolin in human primary dermal keratinocytes and fibroblasts.kaolin is a clay mineral with the chemical composition al2si2o5(oh)4. it is an important industrial material, and is also used as a white cosmetic pigment. we previously reported that fine particles of kaolin have genotoxic potency to chinese hamster ovary cho aa8 cells, and to the lungs of c57bl/6 j and icr mice. in the present study, we evaluated the genotoxicity of different particle sizes of kaolin using primary normal human diploid epidermal keratinocytes and primary normal human diploid de ...202032322315
dna nanovaccines prepared using lema antigen protect golden syrian hamsters against leptospira lethal infection.nanoparticles (nps) are viable candidates as carriers of exogenous materials into cells via transfection and can be used in the dna vaccination strategy against leptospirosis.202032321154
multiplex secretome engineering enhances recombinant protein production and purity.host cell proteins (hcps) are process-related impurities generated during biotherapeutic protein production. hcps can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. here, we present an effort to create a "clean" chinese hamster ovary (cho) cell by disrupting multiple genes to eliminate hcps. using a model of cho cell protein secretion, we predict that the elimination of unnecessary hcps could have a non-negligible impact on ...202032313013
effects of gentiana delavayi flower extract on app processing in app/ps1 cho cells.gentiana delavayi franch. (gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. in this study we investigated the influence of g. delavayi flower extract on amyloid precursor protein (app) processing at molecular and cellular levels. app/ps1 chinese hamster ovary (cho) cells were treated with chloroform extract of g. delavayi flower ...202032378555
expression vector cassette engineering for recombinant therapeutic production in mammalian cell systems.human tissue plasminogen activator was the first recombinant therapy protein that successfully produced in chinese hamster ovary cells in 1986 and approved for clinical use. since then, more and more therapeutic proteins are being manufactured in mammalian cells, and the technologies for recombinant protein production in this expression system have developed rapidly, with the optimization of both upstream and downstream processes. one of the most promising strategies is expression vector cassett ...202032372203
one-step enrichment of intact glycopeptides from glycoengineered chinese hamster ovary cells.recently, the glycoproteomic analysis of intact glycopeptides has emerged as an effective approach to decipher the glycan modifications of glycoproteins at the site-specific level. a rapid method to enrich intact glycopeptides is essential for the analysis of glycoproteins, especially for biopharmaceutical proteins. in this study, we established a one-step method for the rapid capture of intact glycopeptides for analysis by mass spectrometry. compared to the conventional sequential enrichment me ...202032363175
an efficient screening system in yeast to select a hyperactive piggybac transposase for mammalian applications.as non-viral transgenic vectors, the piggybac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. however, further improvements in transpose activity are required for industrialization and clinical applications. herein, we established a one-plasmid effective screening system and a two ...202032357554
kcnq1 antibodies for immunotherapy of long qt syndrome type 2.patients with long qt syndrome (lqts) are predisposed to life-threatening arrhythmias. a delay in cardiac repolarization is characteristic of the disease. pharmacotherapy, implantable cardioverter-defibrillators, and left cardiac sympathetic denervation are part of the current treatment options, but no targeted therapy for lqts exists to date. previous studies indicate that induced autoimmunity against the voltage-gated kcnq1 k+ channels accelerates cardiac repolarization.202032354382
dynamic modeling of cho cell metabolism using the hybrid cybernetic approach with a novel elementary mode analysis strategy.chinese hamster ovary (cho) cell culture has a major importance on the production of biopharmaceuticals, including recombinant therapeutic proteins such as monoclonal antibodies (mab). mathematical modeling of biological systems can successfully assess metabolism complexity while providing logical and systematic methods for relevant genetic target and culture parameter identification toward cell growth and productivity improvements. most modeling approaches on cho cells have been performed under ...202032351947
subphysiological temperature induces pervasive alternative splicing in chinese hamster ovary cells.rna sequencing (rnaseq) has been widely used to associate alterations in chinese hamster ovary (cho) cell gene expression with bioprocess phenotypes; however, alternative messenger rna (mrna) splicing, has thus far, received little attention. in this study, we utilized rnaseq for transcriptomic analysis of a monoclonal antibody (mab) producing cho k1 cell line subjected to a temperature shift. more than 2,465 instances of differential splicing were observed 24 hr after the reduction of cell cult ...202032346860
proteoglycan-dependent endo-lysosomal fusion affects intracellular survival of salmonella typhimurium in epithelial cells.proteoglycans (pgs) are glycoconjugates which are predominately expressed on cell surfaces and consist of glycosaminoglycans (gags) linked to a core protein. an initial step of gags assembly is governed by the β-d-xylosyltransferase enzymes encoded in mammals by the xylt1/xylt2 genes. pgs are essential for the interaction of a cell with other cells as well as with the extracellular matrix. a number of studies highlighted a role of pgs in bacterial adhesion, invasion, and immune response. in this ...202032411142
chromosome-scale scaffolds for the chinese hamster reference genome assembly to facilitate the study of the cho epigenome.the chinese hamster genome serves as a reference genome for the study of chinese hamster ovary (cho) cells, the preferred host system for biopharmaceutical production. recent re-sequencing of the chinese hamster genome resulted in the refseq picr meta-assembly, a set of highly accurate scaffolds that filled over 95% of the gaps in previous assembly versions. however, these scaffolds did not reach chromosome-scale due to the absence of long-range scaffolding information during the meta-assembly p ...202032410221
the relation of bleomycin delivery efficiency to microbubble sonodestruction and cavitation spectral characteristics.the concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. experiments were conducted on chinese hamster ovary cells coadministered with sonovue microbubbles. detailed analysis of the scattering and attenuation temporal functions culminated in q ...202032385397
receptor-targeted photodynamic therapy of glucagon-like peptide 1 receptor-positive lesions.treatment of hyperinsulinemic hypoglycemia is challenging. surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism is invasive and carries major risks of morbidity. medication to treat nesidioblastosis and diffuse congenital hyperinsulinism has varying efficacy and causes significant side effects. here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing β-cells by receptor-targeted photodynamic therapy (rtpdt) with exend ...202032385165
combining lipoic acid to methylene blue reduces the warburg effect in cho cells: from tca cycle activation to enhancing monoclonal antibody production.the warburg effect, a hallmark of cancer, has recently been identified as a metabolic limitation of chinese hamster ovary (cho) cells, the primary platform for the production of monoclonal antibodies (mab). metabolic engineering approaches, including genetic modifications and feeding strategies, have been attempted to impose the metabolic prevalence of respiration over aerobic glycolysis. their main objective lies in decreasing lactate production while improving energy efficiency. although yield ...202032298377
electroceutical silk-silver gel to eradicate bacterial infection.with more than 50% of bacteria resistant to standard antibiotics, new strategies to treat bacterial infection and colonization are needed. based on the concept of targeting the bacteria synergistically on various fronts, it is hypothesized that an electrical insult associated with antibacterial materials may be a highly effective means of killing bacteria. in this work, an injectable conductive gel based on silk fibroin (sf) and silver nanoparticles (ag-nps) is synthesized, capable of coating a ...202032293155
immunogenicity risk assessment for an engineered human cytokine analogue expressed in different cell substrates.the purpose of this article is to illustrate how performance of an immunogenicity risk assessment at the earliest stage of product development can be instructive for critical early decision-making such as choice of host system for expression of a recombinant therapeutic protein and determining the extent of analytical characterization and control of heterogeneity in co- and post-translational modifications. application of a risk-based approach for a hypothetical recombinant dna analogue of a hum ...202032291556
optimization of parameters affecting on cho cell culture producing recombinant erythropoietin.several factors may affect erythropoietin (epo) sugar structures including designing cell culture procedure, ph, concentration of additives, dissolved oxygen, and other physicochemical parameters. in this study, we investigated the influence of changes in effective parameters and compounds on the growth rate of chinese hamster ovary cell (cho) cells producing recombinant epo. cell culture was performed at different temperature, buffering conditions, and varied concentrations of additives such as ...202032336186
patches and blebs: a comparative study of the composition and biophysical properties of two plasma membrane preparations from cho cells.this study was aimed at preparing and characterizing plasma membranes (pm) from chinese hamster ovary (cho) cells. two methods of pm preparation were applied, one based on adhering cells to a poly-lysine-coated surface, followed by hypotonic lysis and removal of intracellular components, so that pm patches remain adhered to each other, and a second one consisting of bleb induction in cells, followed by separation of giant plasma membrane vesicles (gpmv). both methods gave rise to pm in sufficien ...202032290157
naturally occurring variants in the transmembrane and cytoplasmic domains of the human coxsackie- and adenovirus receptor have no impact on virus internalisation.the coxsackie- and adenovirus receptor (car) mediates homophilic cell-cell contacts and susceptibility to both human pathogenic viruses through its membrane-distal immunoglobulin domain. in the present study, we screened five missense variants of the human car gene for their influence on adenovector or coxsackievirus entry into chinese hamster ovary cells. the car variants facilitated virus internalisation to a similar extent as wild type car. this underlines car's presumed invariance and essent ...202032334832
a high-resolution measurement of nucleotide sugars by using ion-pair reverse chromatography and tandem columns.n-linked glycosylation is a cellular process transferring sugars from glycosyl donors to proteins or lipids. biopharmaceutical products widely produced by culturing mammalian cells such as chinese hamster ovary (cho) cells are typically glycosylated during biosynthesis. for some biologics, the n-linked glycan is a critical quality attribute of the drugs. nucleotide sugars are the glycan donors and impact the intracellular glycosylation process. in current analytical methods, robust separation of ...202032300845
development of a scale-up strategy for chinese hamster ovary cell culture processes using the kl a ratio as a direct indicator of gas stripping conditions.herein, we described a scale-up strategy focused on the dissolved carbon dioxide concentration (dco2 ) during fed-batch cultivation of chinese hamster ovary cells. a fed-batch culture process for a 2000-l scale stainless steel (ss) bioreactor was scaled-up from similarly shaped 200-l scale bioreactors based on power input per unit volume (p/v). however, during the 2000-l fed-batch culture, the dco2 was higher compared with the 200-l scale bioreactor. therefore, we developed an alternative approa ...202032298540
a new class of quadruplex dna-binding nickel schiff base complexes.we have prepared six new nickel schiff base complexes via reactions of substituted benzophenones with different diamines in the presence of nickel(ii). these new complexes were then reacted with 1-(2-choroethyl)piperidine to afford a further six novel nickel(ii) schiff base complexes bearing pendant ethylpiperidine groups. the complexes bearing the ethylpiperidine moieties had greater solubility in water, and were therefore suitable for use in dna binding experiments. esi mass spectra of solutio ...202032219227
the effect of amino acid supplementation in an industrial chinese hamster ovary process.the main goal in biosimilar development is to increase chinese hamster ovary (cho) viability and productivity while maintaining product quality. despite media and feed optimization during process development, depletion of amino acids still occurs. the aim of the work was to optimize an existing industrial fed batch process by preventing shortage of amino acids and to gather knowledge about cho metabolism. several process outputs were evaluated such as cell metabolism, cell viability, monoclonal ...202032274904
temperature down-shift modifies expression of upr-/erad-related genes and enhances production of a chimeric fusion protein in cho cells.low culture temperature enhances the cell-specific productivity of chinese hamster ovary (cho) cells expressing varied recombinant (r-) proteins, but the mechanisms remain unclear. regulation of unfolded protein response (upr) pathway genes, such as transcriptional regulatory factors and endoplasmic reticulum (er)-resident proteins, appear to be involved in the improvements of r-protein production under low temperature conditions. the transcriptional regulation of upr-specific targets is studied ...202032271992
nutrient supplementation strategy improves cell concentration and longevity, monoclonal antibody production and lactate metabolism of chinese hamster ovary cells.a careful selection of culture mediums and feeds has become necessary to maximize yields of recombinant proteins during bioprocesses of mammalian cells. supplements contain a variety of concentrate nutrients, and their beneficial effects vary according to recombinant cell lines. in this study, the effects of powerfeed a on growth kinetics, productivity and cellular metabolism were evaluated for two chinese hamster ovary cell lines producing a monoclonal antibody in a batch culture. supplemented ...202032223359
cytotoxicity of halogenated tyrosyl compounds, an emerging class of disinfection byproducts.halogenated amino acids and peptides are an emerging class of disinfection byproducts (dbps), having been detected in drinking water and in washed food products. however, the toxicological significance of these emerging dbps remains unclear. in this study, the cytotoxicity of eight halogenated tyrosyl compounds was investigated in chinese hamster ovary (cho) cells using real-time cell analysis (rtca). dihalogenated tyrosyl compounds are more cytotoxic than their monohalogenated analogues. the cy ...202032200635
validation and identification of reference genes in chinese hamster ovary cells for fc-fusion protein production.in order to reveal potential genotype-phenotype relationship, rt-qpcr reactions are frequently applied which require validated and reliable reference genes. with the investigation on long-term passage and fed-batch cultivation of cho cells producing an fc-fusion protein, four new reference genes-akr1a1, gpx1, aprt, and rps16, were identified from 20 candidates with the aid of genorm, normfinder, bestkeeper, and δct programs and methods. this article provided more verified options in reference ge ...202032216463
pharmacological properties of whale shark (rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: interaction with mrap1 and mrap2.in the current study, the whale shark (ws; rhincodon typus) melanocortin-2 receptor (mc2r) co-expressed with wsmrap1 in chinese hamster ovary (cho) cells could be stimulated in a dose dependent manner by acth(1-24) with an ec50 of 2.6 × 10-10 m ± 9.7 × 10-11. when the receptor was expressed alone, stimulation was only observed at [10-6 m]. a comparable increase in sensitivity to stimulation by srdes-ac-αmsh was also observed when the receptor was co-expressed with wsmrap1. in addition, co-expres ...202032213301
a metabolic network-based approach for developing feeding strategies for cho cells to increase monoclonal antibody production.chinese hamster ovary (cho) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. to date, a variety of metabolic engineering approaches have been used to improve the productivity of cho cells. while genetic manipulations are potentially laborious in mammalian cells, rational design of cho cell culture medium or efficient fed-batch strategies are more popular approaches for bioprocess optimization. in this study, ...202032211960
expanding the chinese hamster ovary cell long noncoding rna transcriptome using rnaseq.our ability to study chinese hamster ovary (cho) cell biology has been revolutionised over the last decade following the development of next generation sequencing technology and publication of reference dna sequences for cho cells and the chinese hamster. rna sequencing has not only enabled the association of transcript expression with bioreactor conditions and desirable bioprocess phenotypes but played a key role in the characterisation of protein coding and small noncoding rnas. the annotation ...202032558938
toxicity of chlorinated algal-impacted waters: formation of disinfection byproducts vs. reduction of cyanotoxins.seasonal algal blooms in surface waters can impact water quality through an input of algal organic matter (aom) to the pool of dissolved organic matter as well as the release of cyanotoxins. the formation and speciation of disinfection byproducts (dbps) during chlorination of algal-impacted waters, collected from growth of microcystis aeruginosa were studied. second-order rate constants for the reactions of microcystins (mcs) with chlorine and bromine were determined. finally, the toxicity of ch ...202032771689
cisplatin decreases enac activity contributing to renal salt wasting syndrome.cisplatin (cddp) is an important anticancer drug. a common side effect of cddp is renal salt and water-wasting syndrome (rsws). the origin of rsws is obscure. emerging evidence, though, suggests that broad inhibition of sodium transport proteins by cddp may result in decreases in tubular reabsorption, causing increases in sodium and water excretion. in this sense, cddp would be acting like a diuretic. the effect of cddp on the epithelial na+ channel (enac), which is the final arbiter fine-tuning ...202032752278
voluhemins, new inhibitors of sterol o-acyltransferase, produced by volutella citrinella bf-0440.new compounds, designated voluhemins a (1) and b (2), are isolated from the culture broth of the fungal strain volutella citrinella bf-0440 along with structurally related known nk12838 (3). spectroscopic data, including 1d and 2d nmr, elucidated their structures. compounds 1-3 have a common indoline-diterpene core and two additional isoprenyl moieties. compounds 1 and 3 contain a hemiaminal unit, while 2 is o-methylated 1. their inhibitory activities toward sterol o-acyltransferase (soat) 1 and ...202032467602
rich production media as a platform for cho cell line development.recent cell culture media for mammalian cells can be abundantly formulated with nutrients supporting production, but such media can be limited to use in host cell culture, transfection, cell cloning, and cell growth under the low cell density conditions. in many cases, appropriate platform media are used for cell line development, and then replaced with rich media for production. in this study, we demonstrate rich chemically defined media for chinese hamster ovary (cho) cells that are suitable a ...202032415509
insulin degrading enzyme (ide) expressed by chinese hamster ovary (cho) cells is responsible for degradation of insulin in culture media.chinese hamster ovary (cho) cells cultured in serum-free chemically-defined media (cdm) are used for manufacturing of therapeutic proteins. growth factors, such as insulin are commonly utilized in manufacturing platforms to enhance cho cell viability and growth. here we report that insulin is degraded in the culture media over time mainly due to the activity of the insulin degrading enzyme (ide). insulin degradation was faster in cell lines that released more ide, which negatively impacted cell ...202032526262
biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study.process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. this case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-l scale (process a, n = 5) to intensified processing schemes at both 1000-l (process b, n = 8) and 2000-l scales (process c, n = 3) for the production of a monoclonal antibody by a chinese hamster ovary cell line. for the upstream part of the process, we implemented an inte ...202032425110
synergistic and antagonistic interactions among organic and metallic components of the ambient particulate matter (pm) for the cytotoxicity measured by chinese hamster ovary cells.although pm2.5 toxicity is known to be related to its chemical composition, the effect of interactions among various particles' components on the toxicity is not well explored. to understand these interactions, especially metals and organic compounds on pm2.5 cytotoxicity, we chose several redox-active substances known to be present in the ambient particles such as metals (cu, fe, and mn) and quinones [9,10-phenanthraquinone (pq), 1,2-naphthoquinone (1,2-nq), 1,4-naphthoquinone (1,4-nq), and 5-h ...202032474273
modulation of acid-sensing ion channels by hydrogen sulfide.acid-sensing ion channels (asics) have been implicated in many physiological and patho-physiological processes like synaptic plasticity, inflammation, pain perception, stroke-induced brain damage and, drug-seeking behaviour. although asics have been shown to be modulated by gasotransmitters like nitric oxide (no), their regulation by hydrogen sulfide (h2s) is not known. here, we present strong evidence that h2s potentiates asics-mediated currents. low ph-induced current in chinese hamster ovary ...202032446393
production of integrin αiibβ3 in stably transfected and clonal chinese hamster ovary cells for functional and structural studies. 202032445462
development of a proline-based selection system for reliable genetic engineering in chinese hamster ovary cells.chinese hamster ovary (cho) cells are the superior host cell culture models used for the bioproduction of therapeutic proteins. one of the prerequisites for bioproduction using cho cell lines is the need to generate stable cho cell lines with optimal expression output. antibiotic selection is commonly employed to isolate and select cho cell lines with stable expression, despite its potential negative impact on cellular metabolism and expression level. herein, we present a novel proline-based sel ...202032470293
gene editing in cho cells to prevent proteolysis and enhance glycosylation: production of hiv envelope proteins as vaccine immunogens.several candidate hiv subunit vaccines based on recombinant envelope (env) glycoproteins have been advanced into human clinical trials. to facilitate biopharmaceutical production, it is necessary to produce these in cho (chinese hamster ovary) cells, the cellular substrate used for the manufacturing of most recombinant protein therapeutics. however, previous studies have shown that when recombinant env proteins from clade b viruses, the major subtype represented in north america, europe, and oth ...202032470085
functional production of human antibody by the filamentous fungus aspergillus oryzae.monoclonal antibodies (mabs) as biopharmaceuticals take a pivotal role in the current therapeutic applications. generally mammalian cell lines, such as those derived from chinese hamster ovaries (cho), are used to produce the recombinant antibody. however, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. aspergillus oryzae, a filamentous fungus recognized as a gras (generally regarded as safe) organism, has an ability to secrete a ...202032514366
impacts on product quality attributes of monoclonal antibodies produced in cho cell bioreactor cultures during intentional mycoplasma contamination events.a mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2-µm filters used in the clarification of harvested cell culture fluid. previously, we reported a study regarding the ability of mycoplasma arginini to persist in a single-use, perfusion rocking bioreactor system containing a chinese hamster ovary (cho) dg4 ...202032436993
overexpression of the mitochondrial pyruvate carrier reduces lactate production and increases recombinant protein productivity in cho cells.chinese hamster ovary (cho) cells are characterized by a low glucose catabolic efficiency, resulting in undesirable lactate production. here, it is hypothesized that such low efficiency is determined by the transport of pyruvate into the mitochondria. the mitochondrial pyruvate carrier (mpc), responsible for introducing pyruvate into the mitochondria, is formed by two subunits, mpc1 and mpc2. stable cho cell lines, overexpressing the genes of both subunits, were constructed to facilitate the ent ...202032436990
a site-specific integration reporter system that enables rapid evaluation of crispr/cas9-mediated genome editing strategies in cho cells.targeted gene knockout and site-specific integration (ssi) are powerful genome editing techniques to improve the development of industrially relevant chinese hamster ovary (cho) cell lines. however, past efforts to perform ssi in cho cells are characterized by low efficiencies. moreover, numerous strategies proposed to boost ssi efficiency in mammalian cell types have yet to be evaluated head to head or in combination to appreciably boost efficiencies in cho. to enable systematic and rapid optim ...202032500600
using metabolomics to identify cell line-independent indicators of growth inhibition for chinese hamster ovary cell-based bioprocesses.chinese hamster ovary (cho) cells are widely used for the production of biopharmaceuticals. efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. in addition to ammonia and lactate, many other metabolites accumulate in cho cell cultures, although their effects remain largely unknown. elucidating these effects has the potential to further improve ...202032429145
small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in chinese hamsters with type 2 diabetes mellitus.type 2 diabetes mellitus (t2dm) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (ir), or both. chinese hamsters have potential value as non-obese animal models of spontaneous t2dm for studying the pathogenesis and molecular characteristics of diabetes. in this study, the molecular characteristics of the chinese hamster diabetes animal model were investigated through small intestine proteomics and ...202032428569
atypical chemokine receptor ackr2-v41a has decreased ccl2 binding, scavenging, and activation, supporting sustained inflammation and increased alzheimer's disease risk.a recent genome-wide association study (gwas) of 59 cerebrospinal fluid (csf) proteins with a connection to alzheimer's disease (ad) demonstrated an association between increased levels of chemokine ligand 2 (ccl2) with an atypical chemokine receptor chemokine-binding protein 2 variant v41a (ackr2-v41a; rs2228467). high levels of ccl2 are associated with increased risk of ad development as well as other inflammatory diseases. in this study we characterized the biological function of the ackr2-v4 ...202032415244
the use of site-specific recombination and cassette exchange technologies for monoclonal antibody production in chinese hamster ovary cells: retrospective analysis and future directions.chinese hamster ovary (cho) cell-based platforms are the most widely used for the biomanufacturing of complex therapeutic proteins, such as monoclonal antibodies (mabs). the development of high-producing clones that are stable and amenable to large-scale cultures is essential to advance a molecule toward clinical evaluation. nevertheless, the generation of such clones generally relies on random integration of an expression plasmid encoding the therapeutic protein gene into the host genome. the e ...202032456474
applications of small molecules in modulating productivity and product quality of recombinant proteins produced using cell cultures.mammalian cell cultures have been used extensively for production of recombinant protein therapeutics such as monoclonal antibodies, fusion proteins and enzymes for decades. small molecules have been investigated as media supplements to improve process productivity and reduce cost of goods. those chemicals can lead to significant yield improvement through different mechanisms such as cell cycle modulation, cellular redox regulation, etc. in addition to productivity, small molecules have also bee ...202032540474
endogenous p21-dependent transgene control for cho cell engineering.numerous engineering efforts have been made in chinese hamster ovary (cho) cells for high level production of therapeutic proteins. however, the dynamic regulation of transgene expression is limited in current systems. here, we investigated the effective regulation of transgene expression in cho cells via targeted integration-based endogenous gene tagging with engineering target genes. targeted integration of egfp-human bcl-2 into the p21 locus effectively reduced the apoptosis, compared with ra ...202032539343
putative phospholipase b-like 2 is not responsible for polysorbate degradation in monoclonal antibody drug products.polysorbates (ps) are surfactants commonly added in a therapeutic protein drug product as excipients to protect proteins from denaturation and aggregation during storage, transportation, and delivery. significant degradation of ps in drug products could lead to shortened drug shelf lives and ps-degrading activity in drug products must be minimized. identification of lipases that degrade ps could lead to better process control in drug manufacturing. in 2016, phospholipase b-like 2 (plbd2) was pro ...202032534029
cellular reference materials for dna damage using electrochemical oxidation.reference materials are needed to quantify the level of dna damage in cells, to assess sources of measurement variability and to compare results from different laboratories. the comet assay (single cell gel electrophoresis) is a widely used method to determine dna damage in the form of strand breaks. here we examine the use of electrochemical oxidation to produce dna damage in cultured mammalian cells and quantify its percentage using the comet assay. chinese hamster ovary (cho) cells were grown ...202032411438
process optimization using high throughput automated micro-bioreactors in chinese hamster ovary cell cultivation.optimization of bioprocesses to increase the yield of desired products is of importance in the biopharmaceutical industry. this can be achieved by strain selection and by developing bioprocess parameters. shake flasks have been used for this purpose. they, however, lack the capability to control the process parameters such as ph and dissolved oxygen (do). this limitation can be overcome with the help of an automated micro-bioreactor. these bioreactors mimic cultivation at a larger scale. one of ...202032478715
activation of oxytocin neurons improves cardiac function in a pressure-overload model of heart failure.this work shows long-term restoration of the hypothalamic oxytocin (oxt) network preserves oxt release, reduces mortality, cardiac inflammation, fibrosis, and improves autonomic tone and cardiac function in a model of heart failure. intranasal administration of oxt in patients mimics the short-term changes seen in animals by increasing parasympathetic-and decreasing sympathetic-cardiac activity. this work provides the essential translational foundation to determine if approaches that mimic parav ...202032478209
adiponectin forms a complex with atherogenic ldl and inhibits its downstream effects.adiponectin, an adipocyte-derived protein, has anti-atherogenic and anti-diabetic effects, but how it confers the anti-atherogenic effects is not well understood. to study the anti-atherogenic mechanisms of adiponectin, we examined whether it interacts with atherogenic low-density lipoprotein (ldl) to attenuate ldl's atherogenicity. l5, the most electronegative subfraction of ldl, induces atherogenic responses similarly to copper-oxidized ldl (oxldl). unlike native ldl endocytosed via the ldl re ...202033144330
bioluminescence as a sensitive electroporation indicator in sub-microsecond and microsecond range of electrical pulses.the cell membrane permeabilization in electroporation studies is usually quantified using fluorescent markers such as propidium iodide (pi) or yo-pro, while chinese hamster ovary cell line frequently serves as a model. in this work, as an alternative, we propose a sensitive methodology for detection and analysis of electroporation phenomenon based on bioluminescence. luminescent mice myeloma sp2/0 cells (transfected using luciferase-pcdna3 plasmid) were used as a cell model. electroporation has ...202033142215
metabolic profiling of cho cell cultures at different working volumes and agitation speeds using spin tube reactors.culture systems based on spin tube reactors have been consolidated in the development of manufacturing processes based on chinese hamster ovary (cho) cells. despite their widespread use, there is little information about the consequences of varying operational setting parameters on the culture performance of recombinant cho cell lines. here we investigated the effect of varying working volumes and agitation speeds on cell growth, protein production and cell metabolism of two clonally-derived cho ...202033169492
a novel lamprey antibody sequence to multimerize and increase the immunogenicity of recombinant viral and bacterial vaccine antigens.hemagglutinin, the major surface protein of influenza viruses, was recombinantly expressed in eukaryotic cells as a monomer instead of its native trimer, and was only immunogenic when administered with an adjuvant [pion et al. 2014]. in order to multimerize this antigen to increase its immunogenicity, a cysteine-rich peptide sequence found at the extreme c-terminus of lamprey variable lymphocyte receptor (vlr)-b antibodies was fused to various recombinant hemagglutinin (rha) proteins from a and ...202033153770
igist-a kinetic bioassay for pertussis toxin based on its effect on inhibitory gpcr signaling.detection of pertussis toxin (ptx) activity is instrumental for the development and manufacturing of pertussis vaccines. these quality and safety measures require thousands of mice annually. here, we describe interference in gαi-mediated signal transduction (igist), an animal-free kinetic bioassay for detection of ptx, by measuring its effect on inhibitory g protein-coupled receptor (gpcr) signaling. ptx adp-ribosylates inhibitory α-subunits of the heterotrimeric g proteins, thereby perturbing t ...202033147407
trans-cinnamaldehyde prevents oxidative stress-induced apoptosis in v79-4 chinese hamster lung fibroblasts through the nrf2-mediated ho-1 activation.oxidative stress, which is characterized by overproduction of reactive oxygen species (ros), is considered a major risk factor associated with fibroblast death in severe lung diseases such as idiopathic pulmonary fibrosis. trans-cinnamaldehyde (tca), the major phytochemical constituent in cinnamon, is known to possess strong anti-oxidant activity. however, whether tca can defend lung fibroblasts against oxidative injury remains to be elucidated. therefore, this study was conducted to investigate ...202033132316
surface antifouling modification on polyethylene filtration membranes by plasma polymerization.surface modification on microporous polyethylene (pe) membranes was facilitated by plasma polymerizing with two hydrophilic precursors: ethylene oxide vinyl ether (eo1v) and diethylene oxide vinyl ether (eo2v) to effectively improve the fouling against mammalian cells (chinese hamster ovary, cho cells) and proteins (bovine serum albumin, bsa). the plasma polymerization procedure incorporated uniform and pin-hole free ethylene oxide-containing moieties on the filtration membrane in a dry single-s ...202033172217
single-cell transcriptome analyses reveal heterogeneity in suspension cultures and clonal markers of cho-k1 cells.cell-to-cell variability in cell populations arises from a combination of intrinsic factors and extrinsic factors related to the milieu. however, the heterogeneity of high cell density suspension cultures for therapeutic protein production remains unknown. here, we illustrate the increasing heterogeneity in the cellular transcriptome of serum-free adapted cho k1 cells during high cell density suspension culture over time without concomitant changes in the genomic sequence. cell cycle-dependent s ...202033179258
osmolality as a lever to modulate the n-glycolylneuraminicacid (neu5gc) level of a recombinant glycoprotein produced in chinese hamster ovary cells.glycoproteins could be highly sialylated, and controlling the sialic acid levels for some therapeutic proteins is critical to ensure product consistency and efficacy. n-acetylneuraminic acid (neu5ac, or nana) and n-glycolylneuraminic acid (neu5gc, or ngna) are the two most common forms of sialic acids produced in mammalian cells. as neu5gc is not produced in humans and can elicit immune responses, minimizing neu5gc formation is important in controlling this quality attribute for complex glycopro ...202032542945
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