Publications

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radioprotective effect of hydroxyl radical scavengers on prokaryotic and eukaryotic cells under various gamma irradiation conditions.the influence of various hydroxyl radical scavengers such as methanol, ethanol and dimethyl sulfoxide on radiation sensitivity of prokaryotic cells (bacteria escherichia coli) and eukaryotic cells (yeast saccharomyces cerevisiae and v79 cells-chinese hamster pulmonary fibroblasts) irradiated by 60co gamma radiation was investigated. the dependence of radiation sensitivity on dose rate in range from 1.8 to 100 gy h-1 was evaluated. survival of cells irradiated by increasing dose rates was followe ...201931812995
novel kcnj10 compound heterozygous mutations causing east/sesame-like syndrome compromise potassium channel function.inwardly rectifying k+ channel 4.1 (kir4.1), encoded by kcnj10, is a member of the inwardly rectifying potassium channel family. in the brain, kir4.1 is predominant in astrocytic glia and accounts for the spatial buffering of k+ released by neurons during action potential propagation. a number of studies have shown that mutations in kcnj10 are associated with sesame/east syndrome, which is characterized by seizures, ataxia, sensorineural deafness, and electrolyte imbalance. herein, we identified ...201931781151
targeting ovarian cancer cell cytotoxic drug resistance phenotype with xanthium strumarium l. extract.emerging drugs aim at targeting the genomic integrity and replication machinery in ovarian cancer. while the antiproliferative activity of xanthium strumarium l. extract (xfc), a traditional herbal medicine, is believed to alter the mitotic apparatus of chinese hamster ovary epithelial cells, its capacity to target and overcome the chemoresistance phenotype in ovarian cancer is unknown. among the cancer cell lines tested, we found that the best proliferation inhibitory effect for xfc was against ...201931827554
a human expression system based on hek293 for the stable production of recombinant erythropoietin.mammalian host cell lines are the preferred expression systems for the manufacture of complex therapeutics and recombinant proteins. however, the most utilized mammalian host systems, namely chinese hamster ovary (cho), sp2/0 and ns0 mouse myeloma cells, can produce glycoproteins with non-human glycans that may potentially illicit immunogenic responses. hence, we developed a fully human expression system based on hek293 cells for the stable and high titer production of recombinant proteins by fi ...201931727983
application of a genome-scale model in tandem with enzyme assays for identification of metabolic signatures of high and low cho cell producers.biopharmaceutical industrial processes are based on high yielding stable recombinant chinese hamster ovary (cho) cells that express monoclonal antibodies. however, the process and feeding regimes need to be adapted for each new cell line, as they all have a slightly different metabolism and product performance. a main limitation for accelerating process development is that the metabolic pathways underlying this physiological variability are not yet fully understood. this study describes the evol ...201931720213
computer-aided strategies for determining the amino acid composition of medium for chinese hamster ovary cell-based biomanufacturing platforms.chinese hamster ovary (cho) cells are used for the production of the majority of biopharmaceutical drugs, and thus have remained the standard industry host for the past three decades. the amino acid composition of the medium plays a key role in commercial scale biologics manufacturing, as amino acids constitute the building blocks of both endogenous and heterologous proteins, are involved in metabolic and non-metabolic pathways, and can act as main sources of nitrogen and carbon under certain co ...201931684012
complexes formed with integrin-α5 and kcnb1 potassium channel wild type or epilepsy-susceptibility variants modulate cellular plasticity via ras and akt signaling.voltage-gated potassium (k+) channel subfamily b member 1 (kcnb1, kv2.1) and integrin-α5 form macromolecular complexes-named integrin-α5-kcnb1 complexes (ikcs)-in the human brain, but their function was poorly understood. here we report that membrane depolarization triggered ikc intracellular signals mediated by small gtpases of the ras subfamily and protein kinase b (akt) to advance the development of filopodia and lamellipodia in chinese hamster ovary cells, stimulate their motility, and enhan ...201931682765
indomethacin enhances type 1 cannabinoid receptor signaling.in addition to its known actions as a non-selective cyclooxygenase (cox) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (cb1r) because of its shared structural features with the known allosteric modulators of cb1r. indomethacin enhanced the binding of [3h]cp55940 to hcb1r and enhanced aea-dependent [35s]gtpγs binding to hcb1r in chinese hamster ovary (cho) cell membranes. indomethacin (1 μm) also enhanced cp55940-depende ...201931680861
identification and profiling of micrornas expressed in oral buccal mucosa squamous cell carcinoma of chinese hamster.micrornas are known to play essential role in the gene expression regulation in cancer. in our research, next-generation sequencing technology was applied to explore the abnormal mirna expression of oral squamous cell carcinoma (oscc) in chinese hamster. a total of 3 novel mirnas (novel-117, novel-118, and novel-135) and 11 known mirnas (crg-mir-130b-3p, crg-mir-142-5p, crg-mir-21-3p, crg-mir-21-5p, crg-mir-542-3p, crg-mir-486-3p, crg-mir-499-5p, crg-mir-504, crg-mir-34c-5p, crg-mir-34b-5p and c ...201931666604
an arginase-based system for selection of transfected cho cells without the use of toxic chemicals.polyamines have essential roles in cell proliferation, dna replication, transcription, and translation processes, with intracellular depletion of putrescine, spermidine, and spermine resulting in cellular growth arrest and eventual death. serum-free media for cho-k1 cells require putrescine supplementation, because these cells lack the first enzyme of the polyamine production pathway, arginase. on the basis of this phenotype, we developed an arginase-based selection system. we transfected cho-k1 ...201931666335
the epitope of pmab-210 is located in platelet aggregation-stimulating domain-3 of pig podoplanin.podoplanin (pdpn)/t1alpha/aggrus, a small mucin-type transmembrane glycoprotein, has been shown to be expressed on lymphatic endothelial cells and epithelial cells of many organs. pdpn is also upregulated in many cancers, and is involved in cancer metastasis and malignant progression. human pdpn possesses three platelet aggregation-stimulating (plag) domains and the plag-like domain, which bind to c-type lectin-like receptor-2 (clec-2). previously, we reported a novel antipig pdpn (ppdpn) monocl ...201931663836
dual role of cofilin in app trafficking and amyloid-β clearance.the accumulation of amyloid-β (aβ) plays a pivotal early event in the pathogenesis of alzheimer's disease (ad). in the brain, neurons produce aβ by the proteolytic processing of amyloid precursor protein (app) through the endocytic pathway, whereas microglia mediate aβ clearance also via endocytic mechanisms. previous studies have shown the critical importance of cofilin, a filamentous actin-severing protein, in actin dynamics and pathogen-triggered endocytic processes. moreover, the binding of ...201931646885
epitope analysis of an antihorse podoplanin monoclonal antibody pmab-219.podoplanin (pdpn), which is a mucin-type membrane glycoprotein, is expressed on lymphatic endothelial cells and epithelial cells of many organs. pdpn is also overexpressed in several malignant cancers, and its expression is associated with cancer progression and poor prognosis. human pdpn possesses three platelet aggregation-stimulating (plag) domains and the plag-like domain (pld), which binds to c-type lectin-like receptor-2 (clec-2). previously, we reported a novel antihorse pdpn (horpdpn) mo ...201931638470
determination of the pathological features of npc1 variants in a cellular complementation test.niemann-pick type c (np-c) is a rare disorder of lipid metabolism caused by mutations within the npc1 and npc2 genes. np-c is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. until now, there is no investigative tool to demonstrate the significance of single variants within the npc genes. hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of npc1 gene variants. chinese ...201931635081
early integration of design of experiment (doe) and multivariate statistics identifies feeding regimens suitable for cho cell line development and screening.in chinese hamster ovary (cho) cell lines, the establishment of the ideal fed-batch regimen promotes metabolic conditions advantageous for the bioproduction of therapeutic molecules. a tailored, cell line-specific feeding scheme is typically defined during process development (pd) activities, through the incorporation of design of experiment (doe) and late stage cell culture approaches. the feeding during early stage cell line development (cld) was a simplified "one-fits-all" design, inherited f ...201931705334
descubrimiento de la proteína reguladora de apoptosis 2 como determinante en la muerte de células tumorales.cancer is a multifactorial disease that constitutes a serious public health problem worldwide. prostate cancer advanced stages are associated with the development of androgen-independent tumors and an apoptosis-resistant phenotype that progresses to metastasis. by studying androgen-independent lymphoid nodule carcinoma of the prostate (lncap) cells induced to apoptosis by serum elimination, we identified the activation of a non-selective cationic channel of 23ps conductance that promotes incomin ...201931695224
tak-925, an orexin 2 receptor-selective agonist, shows robust wake-promoting effects in mice.orexin-producing neurons in the lateral hypothalamus are a critical regulator of sleep/wake states, and their loss is associated with narcolepsy type 1 (nt1). orexin peptides act on two g protein-coupled receptors: orexin 1 receptor (ox1r) and orexin 2 receptor (ox2r). ox2r knockout (ko) mice, but not ox1r ko mice, showed clear narcolepsy-like phenotypes, including fragmented sleep-wake cycles. moreover, ox2r-selective antagonists have been shown to induce sleepiness in mice, and activation of o ...201931654653
a study on enhanced o-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in chinese hamster ovary cells.human chorionic gonadotropin (hcg) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges. the β subunit contains four o-glycosylation sites. previous studies have found that the translation of mrna to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hcg protein in chinese hamster ovary (cho) cells. the effects of o-glycosylation on recombinant hcg protein expression were assessed by ...201931604106
model-driven engineering of n-linked glycosylation in chinese hamster ovary cells.chinese hamster ovary (cho) cells are used for industrial production of protein-based therapeutics (i.e., "biologics"). here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb n-linked glycosylation. specifically, we sought to increase galactose incorporation on a secreted immunoglobulin g (igg) protein. we rationally design, build, and test a total of 23 transgenic cell pools that express single or ...201931596566
efficacy of lenvervimab, a recombinant human immunoglobulin, in treatment of chronic hepatitis b virus infection.the mechanism of action of hepatitis b immunoglobulin (hbig) for chronic hepatitis b (chb) treatment is not fully understood. a clinical trial in japan suggested that hbig therapy might benefit patients with chb.1 lenvervimab, a recombinant monoclonal hbig developed by gc pharma (yongin, south korea), has been screened from an anti-hb-enriched phage-display library cloned from hepatitis b vaccine-boosted human blood cells and was produced in chinese hamster ovary cells.2-4.201931589980
crystal structure of the fab region of a neutralizing antibody against granulocyte-macrophage colony-stimulating factor.an increased level of granulocyte-macrophage colony-stimulating factor has a potential role in the development of autoimmune diseases, and the neutralization of its activity by monoclonal antibodies is a promising therapy for some diseases. here, the crystal structure of the fab region of ev1007, a fully human antibody expressed in chinese hamster ovary cells that was developed from human peripheral blood mononuclear cells, is described. the structure closely resembles that of mb007, which is th ...201931584011
epitope mapping of pmab-225 an anti-alpaca podoplanin monoclonal antibody using flow cytometry.podoplanin (pdpn) is a mucin-type membrane glycoprotein, and possesses three platelet aggregation-stimulating (plag) domains: plag1, plag2, and plag3 at the n-terminus of pdpn, and one or two plag-like domains (plds) in the middle of pdpn. pdpn is expressed on normal tissues, such as podocytes of the kidney and type i alveolar cells of the lung, and is also overexpressed in numerous malignant cancers. previously, we reported a novel anti-alpaca podoplanin (apdpn) monoclonal antibody (mab), pmab- ...201931613697
functional consequences of a kcnt1 variant associated with status dystonicus and early-onset infantile encephalopathy.we identified a novel de novo kcnt1 variant in a patient with early-infantile epileptic encephalopathy (eiee) and status dystonicus, a life-threatening movement disorder. we determined the functional consequences of this variant on the encoded kna 1.1 channel to investigate the molecular mechanisms responsible for this disorder.201931560846
trpa1 ion channel determines beneficial and detrimental effects of gyy4137 in murine serum-transfer arthritis.modulation of nociception and inflammation by sulfide in rheumatoid arthritis and activation of transient receptor potential ankyrin 1 (trpa1) ion channels by sulfide compounds are well documented. the present study aims to investigate trpa1-mediated effects of sulfide donor gyy4137 in k/bxn serum-transfer arthritis, a rodent model of rheumatoid arthritis. trpa1 and somatostatin sst4 receptor wild-type (wt) and knockout mice underwent k/bxn serum transfer and were treated daily with gyy4137. fun ...201931551776
integrated clarification and purification of monoclonal antibodies by membrane based separation of aqueous two-phase systems.therapeutic monoclonal antibodies (mab) are used for the treatment of numerous serious diseases, which have led to an increasing demand over the last decades. increased cell density and mab titer of the cultivation broth lead to great challenges for the subsequent clarification and capture operations in the downstream process. as an alternative approach to the conventional downstream process, a selective mab extraction via an aqueous two-phase system (atps) directly from the cultivation broth of ...201931544846
evaluating the impact of suramin additive on cho cells producing fc-fusion protein.to examine the effects of suramin in cho cell cultures in terms of the cell culture performance and quality of the fc-fusion protein.201931541331
endoglin protein interactome profiling identifies trim21 and galectin-3 as new binding partners.endoglin is a 180-kda glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. heterozygous mutations in the endoglin gene (eng) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectases, and arteriovenous malformations in internal organs. a circulating form of endoglin (alias soluble endoglin, seng), proteolytically released from the ...201931540324
intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis iiia mice.mucopolysaccharidosis type iiia (mps iiia) is a lysosomal storage disorder (lsd) characterized by severe central nervous system (cns) degeneration. the disease is caused by mutations in the sgsh gene coding for the lysosomal enzyme sulfamidase. sulfamidase deficiency leads to accumulation of heparan sulfate (hs), which triggers aberrant cellular function, inflammation and eventually cell death. there is currently no available treatment against mps iiia. in the present study, a chemically modifie ...201931528541
reprogramming aa catabolism in cho cells with crispr/cas9 genome editing improves cell growth and reduces byproduct secretion.chinese hamster ovary (cho) cells are the preferred host for producing biopharmaceuticals. amino acids are biologically important precursors for cho metabolism; they serve as building blocks for proteogenesis, including synthesis of biomass and recombinant proteins, and are utilized for growth and cellular maintenance. in this work, we studied the physiological impact of disrupting a range of amino acid catabolic pathways in cho cells. we aimed to reduce secretion of growth inhibiting metabolic ...201931526854
collaborative study for the calibration of the replacement international standard for pertussis toxin for use in histamine sensitisation and cho cell clustering assays.pertussis toxin (pt) in its detoxified form is one of the major protective antigens in vaccines against bordetella pertussis (whooping cough). reference preparations of native pt are required for the quality control of pertussis vaccines. stocks of the first who international standard (is) for pt (jnih-5) were low and a replacement was required. one candidate material was donated by a vaccine manufacturer to nibsc. it was formulated, lyophilised into sealed glass ampoules and coded 15/126. an in ...201931526657
gpr40 full agonism exerts feeding suppression and weight loss through afferent vagal nerve.gpr40/ffar1 is a gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding behavior. several gpr40 full agonists have been reported to reduce food intake in rodents by regulating gut hormone secretion in addition to their potent glucose-lowering effects; however, detailed mechanisms of feeding suppression are still unknown. in the present study, we characterized t-3601386, a novel compound with potent fu ...201931525244
enhanced transient expression of an anti-cd52 monoclonal antibody in cho cells through utilization of mirna sponge technology.chinese hamster ovary (cho) cells are the dominant mammalian host system for the production of recombinant therapeutic proteins. improving the viable cell density during culture of recombinant cho cells can greatly affect the production yield. micrornas (mirs) -15a and 16-1 are known as negative regulators of multiple genes involved in cell cycle progression and apoptotic inhibition. mir sponges, which act as decoy targets, are transcripts which contain complementary binding sites to the seed re ...201931516510
trehalose uptake and dehydration effects on the cryoprotection of cho-k1 cells expressing tret1.chinese hamster ovary cells (cho-k1 cells) in which the trehalose transporter (tret1) is expressed can have greater cryoprotection than ordinary cho-k1 cells. this study examines the uptake characteristics of trehalose into cells via tret1 and determines the influence of intracellular trehalose on the freeze-thaw viabilities. in our experiments, the intracellular trehalose concentration is controlled by the extracellular trehalose concentration and the immersion time in a freezing solution. in t ...201931499026
mitochondria supply atp to the er through a mechanism antagonized by cytosolic ca2.the endoplasmic reticulum (er) imports atp and uses energy from atp hydrolysis for protein folding and trafficking. however, little is known about how this vital atp transport occurs across the er membrane. here, using three commonly used cell lines (cho, ins1 and hela), we report that atp enters the er lumen through a cytosolic ca2+-antagonized mechanism, or caatier (ca2+-antagonized transport into er). significantly, we show that mitochondria supply atp to the er and a serca-dependent ca2+ gra ...201931498082
bcat1 and bcat2 disruption in cho cells has cell line-dependent effects.in recombinant protein expression using chinese hamster ovary (cho) cells, chemically defined media contain essential amino acids such as branched chain amino acids (bcaas) leucine, isoleucine and valine. availability of amino acids is critical as these are building blocks for protein synthesis. however, breakdown of amino acids can lead to build up of toxic intermediates and metabolites that decrease cell growth, productivity and product quality. bcaa catabolism also hampers the usage of bcaas ...201931465797
novel single-chain variant of antibody against mesothelin established by phage library.mesothelin (msln) shows increased expression in various cancer cells. for clinical application of antibodies as a positron emission tomography (pet) imaging reagent, a human shortened antibody is essential both for avoiding redundant immune responses and for providing rapid imaging. therefore, we cloned a single-chain fragment of variable regions (scfv) from a human-derived gene sequence. this was achieved through the construction of a naïve phage library derived from human tonsil lymphocytes. u ...201931461572
rapid characterization of herg channel kinetics ii: temperature dependence.ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. these temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing, inactivating, and recovery) are commonly represented with q10 coefficients or an eyring relationship. in this article, we assess the validity of these representations by characterizing channel kinetics at multipl ...201931451180
rapid characterization of herg channel kinetics i: using an automated high-throughput system.predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug development and requires a deep understanding of a compound's action on ion channels. in vitro herg channel current recordings are an important step in evaluating the proarrhythmic potential of small molecules and are now routinely performed using automated high-throughput patch-clamp platforms. these machines can execute traditional voltage-clamp protocols aimed at specific gating processes, but the array of protoc ...201931447109
comparing two automated high throughput viable-cell counting systems for cell culture applications.cell counting and viability assessment is an integral part of mammalian cell line development. while manual counting with a hemocytometer is still the gold standard method, its subjectivity and high labor intensity has resulted in its reduced use in favor of automated systems. in addition, some of these automated systems offer multiwell plate based high throughput cell count, which is an asset for biopharmaceutical companies generating hundreds of high-performance cell lines per year. in this st ...201931442502
cathepsin d: removal strategy on protein a chromatography, near real time monitoring and characterisation during monoclonal antibody production.monoclonal antibody (mab) fragmentation is a well-known degradation pathway that results in product loss and can significantly impact product quality, efficacy, or even cause immunogenic reactions, thus potentially endangering patients' health. it is recognised that residual proteases present among host cell proteins (hcps) such as those expressed by chinese hamster ovary (cho) can induce fragmentation, and failure of their complete removal during downstream processing could cause fragmentation ...201931442501
functional and structural characterization of hspb1/hsp27 from chinese hamster ovary cells.small heat shock proteins (shsps) endow cells with stress tolerance. of the various shsps in mammals, hspb1, also known as hsp27, is the most ubiquitous. to examine the structure and function of hspb1, we expressed, purified, and characterized hspb1 from chinese hamster (cricetulus griseus) ovary cells (cghspb1). cghspb1 forms a large oligomeric structure. we observed a monodisperse 16-mer with an elongated sphere, but this is affected by changes in various conditions, including temperature. und ...201931441240
gatifloxacin-1,2,3-triazole-isatin hybrids and their antimycobacterial activities.a series of gatifloxacin-1,2,3-triazole-isatin hybrids 8a-l were designed, synthesized, and screened for their in vitro antimycobacterial activity as well as cytotoxicity toward chinese hamster ovary (cho) cells. the synthesized hybrids showed considerable activity against mtb h37 rv and two mdr-mtb strains with minimal inhibitory concentration (mic) of 0.25-8 μg/ml, and the hybrid 8a (micmtb h37rv : 0.25 μg/ml and micmdr-mtb : 0.5 and 1 μg/ml) was found to be most active against the tested stra ...201931441087
genotoxicity and glucose tolerance induction by acetyltriethylcitrate, substitute plasticizer compared to di(2-ethylhexyl)phthalate.as di(2-ethylhexyl) phthalate (dehp), one of phthalates, is classified as probable human carcinogens in epa, acetyltriethyl citrate(atec), one of aliphatic esters, could be applied to dehp substitute. atec is used as plasticizers in cosmetics and nail products. here, we studied whether atec might have genotoxic potential and induce glucose tolerance as compared to dehp. genotoxicity was determined by ames test with histidine-requiring salmonella typhimurium (ta98, ta100, ta1535 and ta1537) and t ...201931439862
structure-activity relationship study: mechanism of cyto-genotoxicity of nitropyrazole-derived high energy density materials family.stringent toxicological tests have to be performed prior to the industrial development of alternative chemicals particularly high energy dense materials (hedms) such as explosives. the properties (e.g., power, stability) of these compounds are constantly being improved, the current axis of research being the nitration of nitrogen heterocycles leading to hedms such as nitropyrazole-derived molecules. however, except for 3,4,5-trinitropyrazole (3,4,5-tnp), which was shown to be highly toxic in mic ...201931437493
volatile organic compound (voc) emissions of cho and t cells correlate to their expansion in bioreactors.volatile organic compound (voc) emissions were measured from chinese hamster ovary (cho) cell and t cell bioreactor gas exhaust lines with the goal of non-invasively metabolically profiling the expansion process. measurements of cellular 'breath' were made directly from the gas exhaust lines using polydimethylsiloxane (pdms)-coated magnetic stir bars, which underwent subsequent thermal desorption-gas chromatography-mass spectrometry (td-gc-ms) analysis. baseline voc profiles were observed from b ...201931430743
a negative feedback loop regulates integrin inactivation and promotes neutrophil recruitment to inflammatory sites.neutrophils are abundant circulating leukocytes that are rapidly recruited to sites of inflammation in an integrin-dependent fashion. contrasting with the well-characterized regulation of integrin activation, mechanisms regulating integrin inactivation remain largely obscure. using mouse neutrophils, we demonstrate in this study that the gtpase activating protein arap3 is a critical regulator of integrin inactivation; experiments with chinese hamster ovary cells indicate that this is not restric ...201931427445
safety evaluation of pq birch allergy immunotherapy to support product development.pq birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. it consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to l-tyrosine in its microcrystalline form with addition of the adjuvant monophosphoryl lipid a (mpl®). a nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity studies (bacterial reverse mutation and chinese hamster o ...201931425728
uveitis sarcoidosis presumably initiated after administration of shingrix vaccine.uveitis is a form of intraocular inflammation that can occur as a result of infection, injury, vaccination, or as a systemic manifestation of autoimmune or inflammatory diseases including sarcoidosis. sarcoidosis is an inflammatory disease that involves the formation of abnormal granulomas in multiple organ systems. the hallmark of sarcoidosis is a non-caseating granuloma seen on biopsy. here, we present a case report of a healthy 56-year-old caucasian female who presented with uveitis sarcoidos ...201931423396
a comparison of the oligosaccharide structures of antithrombin derived from plasma and recombinant using potelligent® technology.human antithrombin (at) has two isoforms of which the predominant α-form is glycosylated on all four possible glycosylation sites and the lower abundant β-isoform lacks the oligosaccharide on asn135. the main oligosaccharide structure of human at consists of biantennary complex-type oligosaccharides lacking a core fucose. generally, chinese hamster ovary (cho) cells produce recombinant human at (rhat) with core-fucosylated oligosaccharides. however, rhat lacking core-fucose oligosaccharides can ...201931423004
clonal variations in cho igf signaling investigated by silac-based phosphoproteomics and lfq-ms.chinese hamster ovary (cho) cells are commonly used for the production of monoclonal antibodies. omics technologies have been used to elucidate cellular switch points which result in higher monoclonal antibody (mab) productivity and process yields in cho and other biopharmaceutical production cell lines such as human or mouse. currently, investigations of the phosphoproteome in cho cell lines are rare yet could provide further insights into cellular mechanisms related to target product expressio ...201931420692
bell-shaped agonist activation of 5-ht1a receptor-coupled gαi3 g-proteins: receptor density-dependent switch in receptor signaling.a previous study observed bell-shaped concentration-response isotherms for activation of gαi3 g-protein subunits by high efficacy 5-ht1a receptor agonists in a chinese hamster ovary (cho) cell line expressing high levels of these receptors. this suggested that a signaling switch took place in that cell line (from gαi3 to activation of other g-proteins) but it was unclear if such effects are observed for 5-ht1a receptors in other cellular environments. here, using an antibody capture-based [35s]g ...201931376526
clostridium perfringens epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein.a variant form of clostridium perfringens epsilon toxin (y30a-y196a) with mutations, which shows reduced binding to madin-darby canine kidney (mdck) cells and reduced toxicity in mice, has been proposed as the next-generation enterotoxaemia vaccine. here we show that, unexpectedly, the y30a-y196a variant does not show a reduction in toxicity towards chinese hamster ovary (cho) cells engineered to express the putative receptor for the toxin (myelin and lymphocyte protein; mal). the further additi ...201931372245
exploring the n-glycosylation profile of glycoprotein b from human cytomegalovirus expressed in cho and nicotiana tabacum by-2 cells.the ability to control the glycosylation pattern of recombinant viral glycoproteins represents a major prerequisite before their use as vaccines. the aim of this study consisted of expressing the large soluble ectodomain of glycoprotein b (gb) from human cytomegalovirus (hmcv) in nicotiana tabacum bright yellow-2 (by-2) suspension cells and of comparing its glycosylation profile with that of gb produced in chinese hamster ovary (cho) cells. gb was secreted in the by-2 culture medium at a concent ...201931370181
cellular targeting of bispecific antibody-functionalized poly(ethylene glycol) capsules: do shape and size matter?in the present study, a capsule system that consists of a stealth carrier based on poly(ethylene glycol) (peg) and functionalized with bispecific antibodies (bsabs) is introduced to examine the influence of the capsule shape and size on cellular targeting. hollow spherical and rod-shaped peg capsules with tunable aspect ratios (ars) of 1, 7, and 18 were synthesized and subsequently functionalized with bsabs that exhibit dual specificities to peg and epidermal growth factor receptor (egfr). dosim ...201931369234
gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells.microorganisms in animal gut produce unusual fatty acids from the ingested diet. two types of hydroxy fatty acids (hfas), 10-hydroxy-cis-12-octadecenoic acid (hya) and 10-hydroxy-octadecanoic acid (hyb), are linoleic acid (la) metabolites produced by lactobacillus plantarum. in this study, we investigated the metabolism of these hfas in mammalian cells. when chinese hamster ovary (cho) cells were cultured with hya, approximately 50% of the supplemented hya disappeared from the dish within 24 h. ...201931351225
germinality does not necessarily define mab expression and thermal stability.the production potential of recombinant monoclonal antibody (mab) expressing cell lines depends, among other factors, on the intrinsic antibody structure determined by the amino acid sequence. in this study, we investigated the influence of somatic mutations in the v(d)j sequence of four individual, mature model mabs on the expression potential. therefore, we defined four couples, each consisting of one naturally occurring mab (2g12, ustekinumab, 4b3, and 2f5) and the corresponding germline-deri ...201931350616
predicting industrial-scale cell culture seed trains-a bayesian framework for model fitting and parameter estimation, dealing with uncertainty in measurements and model parameters, applied to a nonlinear kinetic cell culture model, using an mcmc method.for production of biopharmaceuticals in suspension cell culture, seed trains are required to increase cell number from cell thawing up to production scale. because cultivation conditions during the seed train have a significant impact on cell performance in production scale, seed train design, monitoring, and development of optimization strategies is important. this can be facilitated by model-assisted prediction methods, whereby the performance depends on the prediction accuracy, which can be i ...201931347693
an unconventional uptake rate objective function approach enhances applicability of genome-scale models for mammalian cells.constraint-based modeling has been applied to analyze metabolism of numerous organisms via flux balance analysis and genome-scale metabolic models, including mammalian cells such as the chinese hamster ovary (cho) cells-the principal cell factory platform for therapeutic protein production. unfortunately, the application of genome-scale model methodologies using the conventional biomass objective function is challenged by the presence of overly-restrictive constraints, including essential amino ...201931341637
pmab-235: a monoclonal antibody for immunohistochemical analysis against goat podoplanin.sensitive and specific monoclonal antibodies (mabs) against not only human but also mouse, rat, rabbit, dog, cat, bovine, pig, and horse podoplanins (pdpns) have been established in our previous studies. however, anti-goat pdpn (gpdpn) has not been established yet. pdpn has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses; therefore, mabs for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues are needed. although we recently demon ...201931338471
fabrication of amyloid-β-secreting alginate microbeads for use in modelling alzheimer's disease.according to the amyloid cascade hypothesis, the earliest trigger in the development of alzheimer's disease (ad) is the accumulation of toxic amyloid-β (aβ) fragments, eventually leading to the classical features of the disease: amyloid plaques, neurofibrillary tangles and synaptic and neuronal loss. the lack of relevant non-transgenic preclinical models reflective of disease progression is one of the main factors hindering the discovery of effective drug treatments. to this end, we have develop ...201931329175
egf receptor stalls upon activation as evidenced by complementary fluorescence correlation spectroscopy and fluorescence recovery after photobleaching measurements.to elucidate the molecular details of the activation-associated clustering of epidermal growth factor receptors (egfrs), the time course of the mobility and aggregation states of egfp tagged egfr in the membranes of chinese hamster ovary (cho) cells was assessed by in situ mobility assays. fluorescence correlation spectroscopy (fcs) was used to probe molecular movements of small ensembles of molecules over short distances and time scales, and to report on the state of aggregation. the diffusion ...201931323980
activin a-induced cachectic wasting is attenuated by systemic delivery of its cognate propeptide in male mice.in cancer, elevated activin levels promote cachectic wasting of muscle, irrespective of tumor progression. in excess, activins a and b use the myostatin signaling pathway in muscle, triggering a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to atrophy. recently, we demonstrated that local delivery of engineered activin and myostatin propeptides (natural inhibitors of these growth factors) could induce profound muscle hypertrophy in healthy mice. add ...201931322699
influence of environmental conditions on the fusion of cationic liposomes with living mammalian cells.lipid-based nanoparticles, also called vesicles or liposomes, can be used as carriers for drugs or many types of biological macromolecules, including dna and proteins. efficiency and speed of cargo delivery are especially high for carrier vesicles that fuse with the cellular plasma membrane. this occurs for lipid mixture containing equal amounts of the cationic lipid dotap and a neutral lipid with an additional few percents of an aromatic substance. the fusion ability of such particles depends o ...201931319557
expression, purification, and characterization of a human complement component c3 analog that lacks the c-terminal c345c domain.the complement system consists of a series of soluble and cell-surface proteins that serve numerous roles in innate immunity, development, and homeostasis. despite its many functions, the central event in the complement system is the proteolytic activation of the 185 kda complement component 3 (c3) into its opsonin and anaphylatoxin fragments known as c3b (175 kda) and c3a (10 kda), respectively. the c3 protein is comprised of thirteen separate structural domains, several of which undergo extens ...201931319063
coexpression of cmp-sialic acid transporter reduces n-glycolylneuraminic acid levels of recombinant glycoproteins in chinese hamster ovary cells.recombinant glycoproteins expressed in chinese hamster ovary (cho) cells contain two forms of sialic acids; n-acetylneuraminic acid (neu5ac) as a major type and n-glycolylneuraminic acid (neu5gc) as a minor type. the neu5gc glycan moieties in therapeutic glycoproteins can elicit immune responses because they do not exist in human. in the present work, to reduce neu5gc levels of recombinant glycoproteins from cho cell cultures, we coexpressed cytidine-5'-monophosphate-sialic acid transporter (cmp ...201931317538
glyconanoparticles for targeted tumor therapy of platinum anticancer drug.an important requirement to decrease the side effects of chemotherapy drugs is to develop nanocarriers with precise biological functions. in this work, a set of glyconanoparticles was prepared via self-assembly of amphiphilic glycoblock copolymers for the targeted delivery of a hydrophobic chemotherapy drug. well-defined glycoblock copolymers that consist of 1,1-di-tert-butyl 3-(2-(metyloyloxy)ethyl)-butane-1,1,3-tricarboxylate (maetc) together with three different protected-sugar moieties (β-d- ...201931314508
kinetic basis of metformin-mpp interactions with organic cation transporter oct2.organic cation transporter 2 (oct2) clears the blood of cationic drugs. efforts to understand oct2 selectivity as a means to predict the potential of new molecular entities (nmes) to produce unwanted drug-drug interactions typically assess the influence of the nmes on inhibition of transport. however, the identity of the substrate used to assess transport activity can influence the quantitative profile of inhibition. metformin and 1-methyl-4-phenylpyridinium (mpp), in particular, display markedl ...201931313952
disinfection byproducts and their toxicity in wastewater effluents treated by the mixing oxidant of clo2/cl2.mixing oxidant of chlorine dioxide (clo2) and chlorine (cl2) often applied in water disinfection. two secondary wastewater effluents at different ammonium-n levels (0.1 and 1.6 mg n l-1) were treated with the mixing oxidant (clo2/cl2) to evaluate the formation of disinfection byproducts (dbps) and the associated cytotoxicity of treated wastewaters. the total chlorine concentrations of clo2 and cl2 were maintained at 10 mg l-1 as cl2 with varied mixing ratios of clo2 to cl2. the formation of 37 h ...201931302364
bioisosteric ferrocenyl aminoquinoline-benzimidazole hybrids: antimicrobial evaluation and mechanistic insights.phenyl- and bioisosteric ferrocenyl-derived aminoquinoline-benzimidazole hybrid compounds were synthesised and evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive nf54 and multi-drug resistant k1 strains of the human malaria parasite, plasmodium falciparum. all compounds were active against the two strains, generally showing enhanced activity in the k1 strain, with resistance indices less than 1. cytotoxicity studies using chinese hamster ovarian cells revealed ...201931301563
development of a new promoter to avoid the silencing of genes in the production of recombinant antibodies in chinese hamster ovary cells.the production of recombinant proteins in mammalian cell lines is one of the most important areas in biopharmaceutical industry. viral transcriptional promoters are widely used to express recombinant proteins in mammalian cell lines. however, these promoters are susceptible to silencing, thus limiting protein productivity. some cpg islands can avoid the silencing of housekeeping genes; for that reason, they have been used to increase the production of recombinant genes in cells of animal origin. ...201931297150
mode-of-action analysis of the effects induced by nicotine in the in vitro micronucleus assay.nicotine's genotoxic potential has been extensively studied in vitro. while the results of mammalian cell-based studies have inferred that it can potentially damage chromosomes, in general and with few exceptions, adverse dna effects have been observed primarily at supraphysiological concentrations in nonregulatory assays that provide little information on its mode-of-action (moa). in this study, a modern-day regulatory genotoxicity assessment was conducted using a flow cytometry-based in vitro ...201931294873
mir-106b promotes therapeutic antibody expression in cho cells by targeting deubiquitinase cyld.micrornas (mirnas) function as important regulators of major cellular processes, such as cell cycle, proliferation, development, and apoptosis. recently, mirna engineering of chinese hamster ovary (cho) cells has emerged as a promising strategy for enhancing therapeutic antibody production. previously, we have reported that inhibition of deubiquitinase cylindromatosis (cyld) remarkably enhanced the therapeutic antibody production in cho cells. however, the mechanisms regulating cyld in cho cells ...201931292678
cytoplasmic conductivity as a marker for bioprocess monitoring: study of chinese hamster ovary cells under nutrient deprivation and reintroduction.the ability to monitor the status of cells during nutrient limitation is important for optimizing bioprocess growth conditions in batch and fed-batch cultures. the activity level of na+ /k+ atpase pumps and cytoplasm ionic concentrations are directly influenced by the nutrient level, and thus, cytoplasm conductivity can be used as a markerless indicator of cell status. in this work, we monitored the change in cytoplasm conductivity of chinese hamster ovary (cho) cells during nutrient deprivation ...201931286489
model-based optimization of temperature and ph shift to increase volumetric productivity of a chinese hamster ovary fed-batch process.industrial production processes, which utilize mammalian cells for the production of therapeutic proteins are routinely designed to include temperature and ph shifts. the process conditions are shifted away from growth promoting conditions towards a state of decreased metabolic activity. this results in the extension of the cultivation duration and therefore in a higher final product concentration. although the correct timing of these shifts is essential for peak process performance, not many st ...201931277910
analyzing the signaling properties of gar (lepisosteus oculatus) melanocortin receptors: evaluating interactions with mrap1 and mrap2.rt-pcr analysis of gar pituitary and brain indicated that different combinations of gar melanocortin receptor mrnas are present in the same tissues with mrnas for gar mrap1 and gar mrap2. against this background, an objective of this study was to determine whether the ligand sensitivity for either acth or α-msh was affected when gar (g) melanocortin receptors (mcrs) were co-expressed with either of the accessory proteins gmrap1 or gmrap2 in chinese hamster ovary cells. the results indicated that ...201931276671
high-level expression of biologically active human follicle stimulating hormone in the chinese hamster ovary cell line by a pair of tricistronic and monocistronic vectors.recombinant human follicle stimulating hormone (fsh), produced in chinese hamster ovary (cho) cells, is widely used for treatment of fertility disorders and is subject to biosimilars development. cell lines with high specific productivities may simplify the fsh production process. here, we used our previously established expression system based on vector p1.1 to create new cell lines secreting heterodimeric fsh protein. to this end, we linked open reading frames of both fsh subunits by the wild- ...201931276557
novel promoters derived from chinese hamster ovary cells via in silico and in vitro analysis.for the industrial production of recombinant proteins in mammalian cell lines, a high rate of gene expression is desired. therefore, strong viral promoters are commonly used. however, these have several drawbacks as they override cellular responses, are not integrated into the cellular network, and thus can induce stress and potentially epigenetic silencing. endogenous promoters potentially have the advantage of a better response to cellular state and thus a lower stress level by uncontrolled ov ...201931271264
a high-throughput system for transient and stable protein production in mammalian cells.recombinant protein expression and purification is an essential component of biomedical research and drug discovery. advances in automation and laboratory robotics have enabled the development of highly parallel and rapid processes for cell culture and protein expression, purification, and analysis. human embryonic kidney (hek) cells and chinese hamster ovary (cho) cells have emerged as the standard host cell workhorses for producing recombinant secreted mammalian proteins by using both transien ...201931267450
involvement of renal efflux transporter mate1 in renal excretion of flecainide.flecainide, an anti-arrhythmic drug, undergoes renal excretion through active renal tubular secretion in addition to passive glomerular filtration. the contribution of renal uptake and efflux transporters in active renal tubular secretion of flecainide remains unclear except that flecainide is a substrate of human multidrug resistance protein 1 (mdr1). to elucidate renal efflux and uptake transporters involved with active renal tubular secretion of flecainide, we conducted in vitro interaction s ...201931257298
underestimated risk from ozonation of wastewater containing bromide: both organic byproducts and bromate contributed to the toxicity increase.ozonation is widely used in wastewater treatment but the associated byproduct formation is a concern. when ozonation is used in the presence of bromide, bromate is generally considered as a major byproduct, and few studies have examined the toxicity of organic byproducts. this study was designed to investigate the cytotoxicity, genotoxicity and dna/rna oxidative damage to chinese hamster ovary (cho) cells of organic extracts from ozonated wastewater in the absence or presence of bromide. ozonati ...201931254885
inhibition of neutral lipid synthesis by avarols from a marine sponge.the effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in chinese hamster ovary (cho) k1 cells were investigated. in intact cho-k1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in cho-k1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (ce) and triglyceride (tg) with ic50 values of ...201931253530
application of mie theory for enhanced size determination of microparticles using optical particle counters.the approach to particle sizing with optical particle counters is often simple interpolation of calibration data. a method is presented that uses the results of mie-theory-based simulations to describe the signal between calibration points, thus reducing the number of necessary calibration points or increasing the sizing accuracy significantly. through the use of mie theory, particles with a refractive index differing from the calibration particles can be measured without an individual calibrati ...201931251277
genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms.the number of approved biopharmaceuticals, where product quality attributes remain of major importance, is increasing steadily. within the available variety of expression hosts, the production of biopharmaceuticals faces diverse limitations with respect to posttranslational modifications (ptm), while different biopharmaceuticals demand different forms and specifications of ptms for proper functionality. with the growing toolbox of genetic engineering technologies, it is now possible to address g ...201931237682
role of network-mediated stochasticity in mammalian drug resistance.a major challenge in biology is that genetically identical cells in the same environment can display gene expression stochasticity (noise), which contributes to bet-hedging, drug tolerance, and cell-fate switching. the magnitude and timescales of stochastic fluctuations can depend on the gene regulatory network. currently, it is unclear how gene expression noise of specific networks impacts the evolution of drug resistance in mammalian cells. answering this question requires adjusting network no ...201931235692
chemical synthesis, proper folding, nav channel selectivity profile and analgesic properties of the spider peptide phlotoxin 1.phlotoxin-1 (phltx1) is a peptide previously identified in tarantula venom (phlogius species) that belongs to the inhibitory cysteine-knot (ick) toxin family. like many ick-based spider toxins, the synthesis of phltx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of phltx1 that allows for a straightforw ...201931234412
identification and characterization of co-purifying cho host cell proteins in monoclonal antibody purification process.host cell proteins (hcps) are process-related impurities derived from the host organism such as chinese hamster ovary (cho) cells used for the production of therapeutic mabs in biopharmaceuticals and potentially pose a risk to patient safety and product efficacy. a number of hcps have been reported as exceptionally difficult to remove and persist across downstream purification operations into final drug product because they exhibit association with mabs. therefore, understanding of hcp impuritie ...201931234041
[increasing transgenic expression in recombinant chinese hamster ovary cells using introns in different directions].the aim of this study is to investigate the effect of the chimeric intron in different directions on the expression of the nerve growth factor (ngf) in recombinant chinese hamster ovary (cho) cells. the chimeric intron that contained the splice sequence of the first intron of the human β-globin and the human immunoglobulin heavy chain variable region intron was used. ngf gene was cloned into the expression vectors containing the chimeric intron in the forward or reverse direction, followed by tr ...201931232003
dna retention on depth filters.depth filtration is a commonly-used bioprocessing unit operation for harvest clarification that reduces the levels of process- and product-related impurities such as cell debris, host-cell proteins, nucleic acids and protein aggregates. since depth filters comprise multiple components, different functionalities may contribute to such retention, making the mechanisms by which different impurities are removed difficult to decouple. here we probe the mechanisms by which double-stranded dna (dsdna) ...201931223185
sniffer cells for the detection of neural angiotensin ii in vitro.neuropeptide release in the brain has traditionally been difficult to observe. existing methods lack temporal and spatial resolution that is consistent with the function and size of neurons. we use cultured "sniffer cells" to improve the temporal and spatial resolution of observing neuropeptide release. sniffer cells were created by stably transfecting chinese hamster ovary (cho) cells with plasmids encoding the rat angiotensin type 1a receptor and a genetically encoded ca2+ sensor. isolated, cu ...201931217439
design and use of chikungunya virus replication templates utilizing mammalian and mosquito rna polymerase i-mediated transcription.chikungunya virus (chikv) is a mosquito-borne alphavirus. it has a positive-sense rna genome that also serves as the mrna for four nonstructural proteins (nsps) representing subunits of the viral replicase. coupling of nsp and rna synthesis complicates analysis of viral rna replication. we developed trans-replication systems, where production of replication-competent rna and expression of viral replicase are uncoupled. mammalian and mosquito rna polymerase i promoters were used to produce noncap ...201931217251
a cross-species whole genome sirna screen in suspension-cultured chinese hamster ovary cells identifies novel engineering targets.high-throughput sirna screens were only recently applied to cell factories to identify novel engineering targets which are able to boost cells towards desired phenotypes. while sirna libraries exist for model organisms such as mice, no cho-specific library is publicly available, hindering the application of this technique to cho cells. the optimization of these cells is of special interest, as they are the main host for the production of therapeutic proteins. here, we performed a cross-species a ...201931213643
probing deviation of adhered membrane dynamics between reconstituted liposome and cellular system.the dynamics of cell-cell adhesion are complicated due to complexities in cellular interactions and intra-membrane interactions. in the present work, we have reconstituted a liposome-based model system to mimic the cell-cell adhesion process. our model liposome system consists of one fluorescein-tagged and one tritc (tetramethyl-rhodamine isothiocyanate)-tagged liposome, adhered through biotin-neutravidin interaction. we monitored the adhesion process in liposomes using förster resonance energy ...201931210021
a simplified techno-economic model for the molecular pharming of antibodies.by the end of 2017, the food and drug administration had approved a total of 77 therapeutic monoclonal antibodies (mabs), most of which are still manufactured today. furthermore, global sales of mabs topped $90 billion in 2017 and are projected to reach $125 billion by 2020. the mabs approved for human therapy are mostly produced using chinese hamster ovary (cho) cells, which require expensive infrastructure for production and purification. molecular pharming in plants is an alternative approach ...201931209856
glycan-masking hemagglutinin antigens from stable cho cell clones for h5n1 avian influenza vaccine development.refocusing of b-cell responses can be achieved by preserving the overall fold of the antigen structure but selectively mutating the undesired antigenic sites with additional n-linked glycosylation motifs for glycan masking the vaccine antigen. we previously reported that glycan-masking recombinant h5 hemagglutinin (rh5ha) antigens on residues 83, 127, and 138 (g127 + g138 or g83 + g127 + 138 rh5ha) elicited broader neutralizing antibodies and protection against heterologous clades/subclades of h ...201930080931
establishment of a high-sensitivity reporter system in mammalian cells for detecting juvenoids using juvenile hormone receptors of daphnia pulex.environmental waters are polluted by various chemicals originating from human activities. recently, the environmental risk of juvenile hormones (jhs) to aquatic microcrustaceans has been recognized by risk assessors and researchers. jh is a major arthropod hormone that regulates molting and reproduction and has analogs that have been used as insect growth regulators. jhs are known to disturb the sex determination system of daphnia, which is a keystone animal in limnetic ecosystems and is not the ...201930203848
suitable hepatitis b vaccine for adult immunization in china: a systematic review and meta-analysis.hepatitis b virus (hbv) infection remains an important public health problem in china, and adults need to be vaccinated. this systematic review and meta-analysis assessed the appropriate immunization of adults in china. only randomized controlled trials (rcts) were eligible, and seroprotection was defined as anti-hbs≥ 10 miu/ml; 18,308 participants in 27 studies were included. relative risk (rr) and random effects models were used. twenty micrograms of hbv vaccine resulted in a better response t ...201930089437
discovery, characterization, and remediation of a c-terminal fc-extension in proteins expressed in cho cells.protein-based biotherapeutics are produced in engineered cells through complex processes and may contain a wide variety of variants and post-translational modifications that must be monitored or controlled to ensure product quality. recently, a low level (~1-5%) impurity was observed in a number of proteins derived from stably transfected chinese hamster ovary (cho) cells using mass spectrometry. these molecules include antibodies and fc fusion proteins where fc is on the c-terminus of the const ...201930148415
recurring genomic structural variation leads to clonal instability and loss of productivity.chinese hamster ovary cells, commonly used in the production of therapeutic proteins, are aneuploid. their chromosomes bear structural abnormality and undergo changes in structure and number during cell proliferation. some production cell lines are unstable and lose their productivity over time in the manufacturing process and during the product's life cycle. to better understand the link between genomic structural changes and productivity stability, an immunoglobulin g producing cell line was s ...201930144379
affinity maturation and characterization of the ofatumumab monoclonal antibody.cd20 molecule, a phosphoprotein with 297 amino acids and four transmembrane domains, is a member of ms4a protein family. anti-cd20 antibodies such as ofatumumab, which have been developed for cancer treatment and has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. rational engineering methods can be applied with reasonable success to improve functional characteristics of antibodies. considering the importance of this iss ...201930160776
pyruvate kinase muscle-1 expression appears to drive lactogenic behavior in cho cell lines, triggering lower viability and productivity: a case study.chinese hamster ovary (cho) cell lines are used to express a variety of therapeutic proteins. however, lactogenic behavior displayed by some cho cell lines during manufacturing processes may result in a decline in viability, productivity, and possible alterations in product quality. in cultured cells, lactate is produced during glycolysis through irreversible conversion of phosphoenolpyruvate to pyruvate and then lactate via sequential function of pyruvate kinase and lactate dehydrogenase (ldh) ...201930179303
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