Publications

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all-optical crosstalk-free manipulation and readout of chronos-expressing neurons.all optical neurophysiology allows manipulation and readout of neural network activity with single-cell spatial resolution and millisecond temporal resolution. neurons can be made to express proteins that actuate transmembrane currents upon light absorption, enabling optical control of membrane potential and action potential signalling. in addition, neurons can be genetically or synthetically labelled with fluorescent reporters of changes in intracellular calcium concentration or membrane potent ...201931057183
insights into the loss of protein sialylation in an fc-fusion protein-producing cho cell bioprocess.sialylation affects circulating half-life, charge distribution, and other biochemical properties of therapeutic glycoproteins. loss of protein sialylation during glycoprotein-producing bioprocesses could lead to a low final protein sialylation level and bring negative effects on subsequent clinical efficacy. in this work, an fc-fusion protein-producing chinese hamster ovary cell fed-batch culture process was studied and insights into the loss of protein sialylation during the fc-fusion protein p ...201931049620
attenuated glutamine synthetase as a selection marker in cho cells to efficiently isolate highly productive stable cells for the production of antibodies and other biologics.chinese hamster ovary (cho) cells are the biopharmaceutical industry's primary means of manufacturing therapeutic proteins, including monoclonal antibodies. the major challenge in cell line development for the production of recombinant biopharmaceuticals lies in generating and isolating rare high-producing stable clones, amongst thousands of low-producing or unstable clones, in a short period of time. one approach to accomplish this is to use the glutamine synthetase (gs) selection system, toget ...201931043114
the glycosylation design space for recombinant lysosomal replacement enzymes produced in cho cells.lysosomal replacement enzymes are essential therapeutic options for rare congenital lysosomal enzyme deficiencies, but enzymes in clinical use are only partially effective due to short circulatory half-life and inefficient biodistribution. replacement enzymes are primarily taken up by cell surface glycan receptors, and glycan structures influence uptake, biodistribution, and circulation time. it has not been possible to design and systematically study effects of different glycan features. here w ...201931040271
direct and indirect effects of exposure to 900 mhz gsm radiofrequency electromagnetic fields on cho cell line: evidence of bystander effect by non-ionizing radiation.the rapid rise in global concerns about the adverse health effects of exposure to radiofrequency radiation (rfr) generated by common devices such as mobile phones has prompted scientists to further investigate the biological effects of these environmental exposures. non-targeted effects (ntes) are responses which do not need a direct exposure to be expressed and are particularly significant at low energy radiations. although ntes of ionizing radiation are well documented, there are scarcely any ...201931036329
ouabain enhances cell-cell adhesion mediated by β1 subunits of the na+,k+-atpase in cho fibroblasts.adhesion is a crucial characteristic of epithelial cells to form barriers to pathogens and toxic substances from the environment. epithelial cells attach to each other using intercellular junctions on the lateral membrane, including tight and adherent junctions, as well as the na+,k+-atpase. our group has shown that non-adherent chinese hamster ovary (cho) cells transfected with the canine β1 subunit become adhesive, and those homotypic interactions amongst β1 subunits of the na+,k+-atpase occur ...201931035668
the less the better: how suppressed base addition boosts production of monoclonal antibodies with chinese hamster ovary cells.biopharmaceutical production processes strive for the optimization of economic efficiency. among others, the maximization of volumetric productivity is a key criterion. typical parameters such as partial pressure of co2 (pco2) and ph are known to influence the performance although reasons are not yet fully elucidated. in this study the effects of pco2 and ph shifts on the phenotypic performance were linked to metabolic and energetic changes. short peak performance of qmab (23 pg/cell/day) was ac ...201931032253
establishment of dhfr-deficient hek293 cells for high yield of therapeutic glycoproteins.since the use of protein therapeutics is effective for treating intractable human diseases, the production of biologic therapeutic agents has dramatically increased over the past three decades. the chinese hamster ovary (cho) cell lines are the most commonly used host cell expression system for recombinant protein production. high productive and stable clonal cell lines for recombinant protein production have been established from the dhfr-deficient cho cell using the dihydrofolate reductase/met ...201931031194
transcription factor engineering in cho cells for recombinant protein production.the continuous increase of approved biopharmaceutical products drives the development of more efficient recombinant protein expression systems. chinese hamster ovary (cho) cells are the mainstay for this purpose but have some drawbacks, such as low levels of expression. several strategies have been applied to increase the productivity of cho cells with different outcomes. transcription factor (tf) engineering has emerged as an interesting and successful approach, as these proteins can act as mas ...201931030575
phenotypic characterization of a novel type 2 diabetes animal model in a shanxi mu colony of chinese hamsters.developing animal models for human diseases is critical for studying complex diseases such as type 2 diabetes mellitus (t2dm). since inbred colonies of chinese hamsters tend toward spontaneous development of diabetes, we investigated them as a possible model.201931025261
proteogenomic annotation of chinese hamsters reveals extensive novel translation events and endogenous retroviral elements.a high-quality genome annotation greatly facilitates successful cell line engineering. standard draft genome annotation pipelines are based largely on de novo gene prediction, homology, and rna-seq data. however, draft annotations can suffer from incorrect predictions of translated sequence, inaccurate splice isoforms, and missing genes. here, we generated a draft annotation for the newly assembled chinese hamster genome and used rna-seq, proteomics, and ribo-seq to experimentally annotate the g ...201931020842
improvements in single-use bioreactor film material composition leads to robust and reliable chinese hamster ovary cell performance.single-use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. however, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. although the leachable bis(2,4-di-tert-butylphenyl)-phosphate (bdtbpp) has been previously shown to inhibit cho cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial ap ...201931017345
a combined cell-free protein synthesis and fluorescence-based approach to investigate gpcr binding properties.fluorescent labeling of de novo synthesized proteins is in particular a valuable tool for functional and structural studies of membrane proteins. in this context, we present two methods for the site-specific fluorescent labeling of difficult-to-express membrane proteins in combination with cell-free protein synthesis. the cell-free protein synthesis system is based on chinese hamster ovary cells (cho) since this system contains endogenous membrane structures derived from the endoplasmic reticulu ...201930969411
genetic and epigenetic variation across genes involved in energy metabolism and mitochondria of chinese hamster ovary cell lines.the increasingdemandfor biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity, and product quality. as these depend on energy generation, here the genomic variation in nuclear genes associated with mitochondria and energy metabolism and the mitochondrial genome of 14 cell lines is investigated. the variants called enable reliable tracing of lineages. unique sequence variations are observed in cell lines adap ...201930969017
incorporation of an intramolecular hydrogen bonding motif in the side chain of antimalarial benzimidazoles.analogues of a novel class of benzimidazoles with an intramolecular hydrogen bonding motif have been synthesized and evaluated in vitro for their antiplasmodium activity against chloroquine-sensitive (nf54) and multi-drug resistant (k1) strains of the human malaria parasite plasmodium falciparum. compounds were also screened for their cytotoxicity towards a mammalian chinese hamster ovarian (cho) cell line. most of the compounds exhibited good antiplasmodium activity (pfnf54 ic50 <1 μm) and were ...201931015908
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
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
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
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
chloramination of iodide-containing waters: formation of iodinated disinfection byproducts and toxicity correlation with total organic halides of treated waters.the formation of iodinated disinfection byproducts (i-dbps) in drinking waters is of a concern due to their higher cyto- and genotoxicity than their chlorinated and brominated analogues. this study investigated the formation of i-dbps under chloramination conditions using preformed chloramine and associated cyto- and geno-toxicities obtained with chinese hamster ovary (cho) cell assay. cyto- and geno-toxicity of the samples were also calculated using dbp toxicity index values and correlated with ...201931484087
consequences of trace metal variability and supplementation on chinese hamster ovary (cho) cell culture performance: a review of key mechanisms and considerations.trace metals are supplied to chemically-defined media (cdm) for optimal chinese hamster ovary (cho) cell culture performance during the production of monoclonal antibodies and other therapeutic proteins. however, lot-to-lot and vendor-to-vendor variability in raw materials consequently leads to an imbalance of trace metals that are supplied to cdm. this imbalance can yield detrimental effects rooted in several primary mechanisms and pathways including oxidative stress, apoptosis, lactate accumul ...201931403183
zinc supplementation increases protein titer of recombinant cho cells.in order to study the impact of zinc and copper on the titer levels of mab and recombinant protein in cho cells, the igg-expressing (dp12) and epo-expressing (sk15) cell lines were cultured in chemically defined media with increasing concentrations of either metal. supplementation with 25 mg/l in cdm media resulted in a significant increase in epo (1.7-fold) and igg (2.6-fold) titers compared to control (no added zinc). titers at this zn concentration in cdm containing the insulin replacing agen ...201931396753
interphase cytogenetic analysis of micronucleated and multinucleated cells supports the premature chromosome condensation hypothesis as the mechanistic origin of chromothripsis.the discovery of chromothripsis in cancer genomes challenges the long-standing concept of carcinogenesis as the result of progressive genetic events. despite recent advances in describing chromothripsis, its mechanistic origin remains elusive. the prevailing conception is that it arises from a massive accumulation of fragmented dna inside micronuclei (mn), whose defective nuclear envelope ruptures or leads to aberrant dna replication, before main nuclei enter mitosis. an alternative hypothesis i ...201931390832
recombinant hemagglutinin produced from chinese hamster ovary (cho) stable cell clones and a pelc/cpg combination adjuvant for h7n9 subunit vaccine development.the novel h7n9 avian influenza a virus has caused human infections in china since 2013; some isolates from the fifth wave of infections have emerged as highly pathogenic avian influenza viruses. recombinant hemagglutinin proteins of h7n9 viruses can be rapidly and efficiently produced with low-level biocontainment facilities. in this study, recombinant h7 antigen was obtained from engineered stable clones of chinese hamster ovary (cho) cells for subsequent large-scale production. the stable cho ...201931383491
treatment with 3-aminobenzamide negates the radiofrequency-induced adaptive response in two cell models.in previous investigations, we demonstrated that pre-exposure of different cell cultures to radiofrequency fields can reduce the damage induced by genotoxic agents, an effect resembling the so-called adaptive response. in this study, we pre-exposed human peripheral blood lymphocytes and chinese hamster lung fibroblast cell line to 1950 mhz, umts (universal mobile telecommunication system) signal, for 20 h, and then treated cultures with mitomycin-c. after confirming the induction of an adaptive ...201931382475
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
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
in vitro cytotoxicity studies of industrial eucalyptus kraft lignins on mouse hepatoma, melanoma and chinese hamster ovary cells.kraft lignin is a polyphenolic compound generated as a by-product from the kraft pulping process in large quantities annually worldwide. in addition to its commercial availability, its structural features make it worth to be considered in the pharmaceutical area. the present study was carried out to evaluate in vitro antioxidant and cytotoxic properties of kraft lignin on mouse hepatoma mh-22a, melanoma b16 (tumor cells) and chinese hamster ovary (cho, non-cancerous) cells. moreover, several ana ...201931125648
application of er stress biomarkers to predict formulated monoclonal antibody stability.for a therapeutic monoclonal antibody (mab) to reach the clinic, the molecule must be produced at an appropriate yield and quality, then formulated to maintain efficacy and stability. the formation of subvisible particles (svps) can impact product stability and is monitored during formulation development; however, the potential of a mab to form such species can be influenced throughout the whole bioprocess. the levels of intracellular endoplasmic reticulum (er) stress perceived by chinese hamste ...201931119893
multiple conserved elements structuring inverted repeats in the mammalian coat color-related gene asip.in the agouti signaling gene protein (asip) of the house mouse (mus musculus), inverted repeat (ir) arrays are known to exist in a non-coding region adjacent to the ventral-specific promoter region and the accompanying two exons (exons 1a and 1a'), which are around 100 kb upstream from the amino acid coding regions of exons 2, 3, and 4. to determine the gene structure of mammalian asip and to elucidate trends in its evolution, non-coding sequences of six rodent (mouse, rat, chinese hamster, squi ...201931116535
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
genotoxicity evaluation of a phragmitis rhizoma extract using a standard battery of in vitro and in vivo assays.a rhizome of phragmites communis trinius has been used in traditional medicine to remove a heat, relieve vomiting and fever, nourish body fluids, and treat diseases like cancers. however, the safety of phragmitis rhizoma has not yet been fully assessed.201931189082
a new heparan sulfate from the mollusk nodipecten nodosus inhibits merozoite invasion and disrupts rosetting and cytoadherence of plasmodium falciparum.despite treatment with effective antimalarial drugs, the mortality rate is still high in severe cases of the disease, highlighting the need to find adjunct therapies that can inhibit the adhesion of plasmodium falciparum-infected erythrocytes (pf-ies).201931188952
metabolomic profiling of cho fed-batch growth phases at 10, 100, and 1,000 l.established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement, and the measurement of physicochemical qualities of the cultivation medium. these methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. however, understanding of the latter is essential for optimization of bioprocess development. our study used lc-ms ...201931184374
site-specific phosphorylation of villin remodels the actin cytoskeleton to regulate sendai viral glycoprotein-mediated membrane fusion.connivance of cellular factors during virus-host cell membrane fusion is poorly understood. we have recently shown that cellular villin plays an important role during membrane fusion of reconstituted sendai virosomes with hepatocytes. here, we employed villin-null chinese hamster ovary (cho) cells, where villin expression led to an increased fusion with virosomes, which was further enhanced due to tyrosine phosphorylation in the presence of c-src. however, the villin rri mutant, lacking actin-se ...201931183850
screening naturally occurring phenolic antioxidants for their suitability as additives to cho cell culture media used to produce monoclonal antibodies.this study identified several antioxidants that could be used in chinese hamster ovary (cho)cell culture media and benefit monoclonal antibody production. the flavan-3-ols, catechin, epicatechin, epigallocatechin gallate and gallocatechin gallate all had no detrimental effect on cell viability at the concentrations tested, and they reduced the final viable cell count with a resulting rise in the cell specific productivity. the flavone, luteolin behave similarly to the flavan-3-ols. resveratrol a ...201931163664
genotoxicity evaluation of tobacco and nicotine delivery products: part two. in vitro micronucleus assay.in this study, a variety of test matrices from tobacco and nicotine delivery products were assessed against a 3r4f kentucky reference cigarette using the in vitro micronucleus assay. testing was conducted using two chinese hamster cell lines (cho and v79), and a human lymphoblastoid cell line (tk6), in accordance with established guidelines. total particulate matter (tpm) from a 3r4f reference cigarette was compared to an electronic cigarette e-liquid, electronic cigarette tpm and tpm from a com ...201931163219
establishment of an anticetacean podoplanin monoclonal antibody pmab-237 for immunohistochemical analysis.podoplanin (pdpn) has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses. therefore, sensitive and specific monoclonal antibodies (mabs) targeting pdpn are needed for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues. recently, anti-pdpn mabs against many species, such as human, mouse, rat, rabbit, dog, cat, bovine, pig, and horse were established in our studies. however, anticetacean (whale) pdpn (wpdpn) has not been established y ...201931161965
bip inducer x: an er stress inhibitor for enhancing recombinant antibody production in cho cell culture.prolonged endoplasmic reticulum (er) stress reduces protein synthesis and induces apoptosis in mammalian cells. when dimethyl sulfoxide (dmso), a specific monoclonal antibody productivity (qmab )-enhancing reagent, is added to recombinant chinese hamster ovary (rcho) cell cultures (gsr cell line), it induces er stress and apoptosis in a dose-dependent manner. to determine an effective er stress inhibitor, three er stress inhibitors (bip inducer x [bix], tauroursodeoxycholic acid, and carbazole) ...201931161665
development of an improved lentiviral based vector system for the stable expression of monoclonal antibody in cho cells.therapeutic monoclonal antibodies (mabs) have become the dominant products in biopharmaceutical industry. mammalian cell expression systems including chinese hamster ovary (cho) cells are the most commonly used hosts for the production of complex recombinant proteins. however, development of stable, high producing cho cell lines suffers from the low expression level and instability of the transgene. the increasing efforts in the development of novel therapeutic antibodies and the advent of biosi ...201931156045
synthesis and characterization of porous structures of rutile tio2 /na0.8ti4o8/na2ti6o13 for biomedical applications.this method involves the use of molding, pressing and sintering techniques applied to different powder mixtures of tio2 with sodium bicarbonate nahco3 (15 wt% and 30 wt% nahco3), to obtain porous structures of rutile tio2/na0.8ti4o8/na2ti6o13 and na0.8ti4o8/na2ti6o13 for possible biomedical implant applications. the method validation includes x-ray diffraction patterns (xrd) analysis refined by the rietveld method using x'pert highscore plus. the surface morphology was observed by using a scanni ...201931193424
tcnst2 encodes a golgi-localized udp-galactose transporter in trypanosoma cruzi.survival and infectivity of trypanosomatids rely on cell-surface and secreted glycoconjugates, many of which contain a variable number of galactose residues. incorporation of galactose to proteins and lipids occurs along the secretory pathway from udp-galactose (udp-gal). before being used in glycosylation reactions, however, this activated sugar donor must first be transported across the endoplasmic reticulum and golgi membranes by a specific nucleotide sugar transporter (nst). in this study, w ...201931190664
insight into the roles of tyrosine on rcho cell performance in fed-batch cultures.tyrosine (tyr), as one of the least soluble amino acids, is essential to monoclonal antibody (mab) production in recombinant chinese hamster ovary (rcho) cell cultures since its roles on maintaining the specific productivity (qmab) and avoiding tyr sequence variants. to understand the effects of tyr on cell performance and its underlying mechanisms, rcho cell-producing mabs were cultivated at various cumulative tyr addition concentrations (0.6 to 5.5 mm) in fed-batch processes. low tyr concentra ...201931190239
small-molecule control of antibody n-glycosylation in engineered mammalian cells.n-linked glycosylation in monoclonal antibodies (mabs) is crucial for structural and functional properties of mab therapeutics, including stability, pharmacokinetics, safety and clinical efficacy. the biopharmaceutical industry currently lacks tools to precisely control n-glycosylation levels during mab production. in this study, we engineered chinese hamster ovary cells with synthetic genetic circuits to tune n-glycosylation of a stably expressed igg. we knocked out two key glycosyltransferase ...201931110306
purification and analytics of a monoclonal antibody from chinese hamster ovary cells using an automated microbioreactor system.monoclonal antibodies (mabs) are one of the most popular and well-characterized biological products manufactured today. most commonly produced using chinese hamster ovary (cho) cells, culture and process conditions must be optimized to maximize antibody titers and achieve target quality profiles. typically, this optimization uses automated microscale bioreactors (15 ml) to screen multiple process conditions in parallel. optimization criteria include culture performance and the critical quality a ...201931107445
ca2+ signal is involved in endothelin-1-induced internalization of endothelin type a receptor expressed in chinese hamster ovary cells.endothelin type a receptor (etar) is internalized upon agonist stimulation; however, the mechanism thereof remains controversial. in this study, we characterized the endothelin-1 (et-1)-induced internalization of etar expressed in chinese hamster ovary cells. et-1 elicited etar internalization and increase in intracellular ca2+ concentration. et-1-induced etar internalization was completely inhibited by a reduction in intracellular and extracellular ca2+ levels and partially suppressed by inhibi ...201931103330
comparative toxicity of organic mixture attached to road deposited sediments: inadequacy of conventionally using individual pollutants to assess comprehensive hazard effects.organic pollutants attached on road deposited sediments (rds) during dry days can be washed-off into stormwater runoff during rainfall events, undermining stormwater reuse safety. previous research studies commonly utilized individual pollutant groups and their quantity to evaluate the hazard effect of pollutants attached to rds in terms of stormwater reuse. since many types of organic pollutants are present together rather than individually, conventional approaches might not permit a comprehens ...201931102843
improvement of growth rates through nucleoside media supplementation of cho clones.chinese hamster ovary (cho) cells are used for the production of therapeutic proteins. this work examines improving passaging growth rate of two cho clones. growth rates were significantly improved for both clones with supplementation of the nucleosides cytidine, hypoxanthine, uridine, and thymidine to the culturing media at the optimal concentration of 100 µm of each nucleoside. we investigated supplementing the same combination of nucleosides to seed bioreactors and production fed batch biorea ...201931115721
improved recombinant protein production by regulation of transcription and protein transport in chinese hamster ovary cells.to identify genes that affected protein expression in chinese hamster ovary (cho) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein.201931114947
reduction of il-2 fragmentation during manufacturing of a novel immunocytokine by doe process optimization.interleukin-2 (il-2) is a potent molecule in cancer therapy. clinical application, however, is limited due to its strong side effects during the treatment. we developed an il-2 variant (il-2v) immunocytokine to circumvent the drawbacks of the current il-2 therapy. during the production of the il-2v immunocytokine in chinese hamster ovary (cho) cells, molecules with fragmented il-2v and therefore reduced cytokine activity can be observed. to control product fragmentation different production proc ...201931180133
impact of mammalian cell culture conditions on monoclonal antibody charge heterogeneity: an accessory monitoring tool for process development.recombinant monoclonal antibodies are predominantly produced in mammalian cell culture bioprocesses. post-translational modifications affect the micro-heterogeneity of the product and thereby influence important quality attributes, such as stability, solubility, pharmacodynamics and pharmacokinetics. the analysis of the surface charge distribution of monoclonal antibodies provides aggregated information about these modifications. in this work, we established a direct injection ph gradient cation ...201931175523
differential effects of bioreactor process variables and purification on the human recombinant lysosomal enzyme β-glucuronidase produced from chinese hamster ovary cells.β-glucuronidase is a lysosomal enzyme and a molecular model of a class of therapeutics approved as enzyme replacement therapies for lysosomal storage diseases. understanding the effect of bioreactor process variables on the production and quality of the biologics is critical for maintaining quality and efficacy of the biotherapeutics. here, we have investigated the effect of three process variables, in a head-to-head comparison using a parallel bioreactor system (n = 8), namely 0.25 mm butyrate ...201931175430
novel short synthetic matrix attachment region for enhancing transgenic expression in recombinant chinese hamster ovary cells.matrix attachment regions (mars) are dna fragments with specific motifs that enhance transgenic expression; however, the characteristics and functions of these elements remain unclear. in this study, we designed and synthesized three short chimeric mars, namely, sm4, sm5, and sm6, with different numbers and orders of motifs on the basis of the features and motifs of previously reported mars, namely, sm1, sm2, and sm3, respectively. expression vectors with six synthetic mars flanking the down or ...201931168866
characterization of a gdp-fucose transporter and a fucosyltransferase involved in the fucosylation of glycoproteins in the diatom phaeodactylum tricornutum.although phaeodactylum tricornutum is gaining importance in plant molecular farming for the production of high-value molecules such as monoclonal antibodies, little is currently known about key cell metabolism occurring in this diatom such as protein glycosylation. for example, incorporation of fucose residues in the glycans n-linked to protein in p. tricornutum is questionable. indeed, such epitope has previously been found on n-glycans of endogenous glycoproteins in p. tricornutum. meanwhile, ...201931164895
limiting the metabolic burden of recombinant protein expression during selection yields pools with higher expression levels.in order to avoid the metabolic burden of protein expression during cell growth, and to avoid potential toxicity of recombinant proteins, microbial expression systems typically utilize regulated expression vectors. in contrast, constitutive expression vectors have usually been utilized for isolation of protein expressing mammalian cell lines. in mammalian systems, inducible expression vectors are typically utilized for only those proteins that are toxic when overexpressed. we developed a tetracy ...201931090257
enhancing expression level and stability of transgene mediated by episomal vector via buffering dna methyltransferase in transfected cho cells.nonviral episomal vectors present attractive alternative vehicles for gene therapy applications. previously, we have established a new type of nonviral episomal vector-mediated by the characteristic motifs of matrix attachment regions (mars), which is driven by the cytomegalovirus (cmv) promoter. however, the cmv promoter is intrinsically susceptible to silencing, resulting in declined productivity during long-term culture. in this study, chinese hamster ovary (cho) cells and dna methyltransfera ...201931074065
usnic acid attenuates genomic instability in chinese hamster ovary (cho) cells as well as chemical-induced preneoplastic lesions in rat colon.usnic acid (ua) is one of the pharmacologically most important compounds produced by several lichen species. to better understand the mechanism of action (moa) of this important substance, this study examined the genotoxicity attributed to ua and its influence on mutagens with varying moa using the micronucleus (mn) test in chinese hamster ovary cells (cho). additional experiments were conducted to investigate the effect of ua on colon carcinogenesis in wistar rats employing the aberrant crypt f ...201931066341
precision of scoring radiation-induced chromosomal aberrations and micronuclei by unexperienced scorers.purpose: dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. the results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used when fast analysis of a large amount of data is needed. the aim of this study was to compare the performance of two radiobiological assays - chromosomal aberrations and micronuclei ...201931140900
oxidative stress and endoreduplication induced by blue light exposure to cho cells.blue light is commonly used for the treatment of neonatal jaundice and as a photodynamic therapy for cancer. in comparison to ultraviolet light, blue light has a lower toxicity due to the differences in photon energies. however, blue light can still be mutagenic to cells. the proposed mechanism suggests blue light exposure induces reactive oxygen species inducing oxidative stress. in this study, we examined how blue light exposure caused genotoxic effects utilizing chinese hamster ovary (cho) ce ...201931138408
evaluation of a single amino acid substitution at position 79 of human ifn-α2b in interferon-receptor assembly and activity.type i interferons (ifns) are homologous cytokines that bind to a cell surface receptor and establish signaling pathways that motivate immune responses. the purpose of the current study is to assess the activity of a novel-engineered ifn-α2b. the crystallographic structure of ifn-α2b and its receptors was acquired from protein data bank. various amino acid substitutions were designed based on structural properties and other biological characteristics of residues to find the most effective amino ...201931135267
characterization of intact glycopeptides reveals the impact of culture media on site-specific glycosylation of epo-fc fusion protein generated by cho-gs cells.with the increasing demand to provide more detailed quality attributes, more sophisticated glycan analysis tools are highly desirable for biopharmaceutical manufacturing. here, we performed an intact glycopeptide analysis method to simultaneously analyze the site-specific n- and o-glycan profiles of the recombinant erythropoietin fc (epo-fc) protein secreted from a chinese hamster ovary glutamine synthetase stable cell line and compared the effects of two commercial culture media, ex-cell (ex) a ...201931062865
comparative toxicity study of a novel non-ionic surfactant, vanillin ethoxylates, and nonylphenol ethoxylates in chinese hamster ovary cells in vitro.surfactants such as alkylphenol polyethoxylates (apeos) and nonylphenol ethoxylates (npeos) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce severe biological toxicity. here, we evaluated for the first time the cytotoxicity, genotoxicity and mitochondrial damage in chinese hamster ovary (cho-k1) cells caused by a novel non-ionic surfactant, vanillin ethoxylates (vaeos), an alternative to apeos. in parallel, the same i ...201931133271
photochemical oxidation of ppcps using a combination of solar irradiation and free available chlorine.the degradation of pharmaceuticals and personal care products (ppcps) by using solar photolysis in the presence of free available chlorine (fac) was investigated in simulated drinking water. the combination of free available chlorine and sunlight irradiation dramatically accelerated the degradation of all the contaminants tested through the generation of hydroxyl radicals, reactive chlorine species (rcs) and ozone. contaminants containing electron-donating moieties degraded quickly and were pref ...201931129545
a flipr assay for discovery of gabaa receptor modulators of natural origin.a fluorometric imaging plate reader (flipr) assay utilizing chinese hamster ovary (cho) cells stably transfected with gabaa receptors of α1β2γ2 subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. validation was performed with pure compounds and extracts known to contain allosteric gabaa receptor modulators. plants extracts that had been previously reported as active in an assay using xenopus la ...201931127604
identification and crispr/cas9 inactivation of the c1s protease responsible for proteolysis of recombinant proteins produced in cho cells.proteolysis associated with recombinant protein expression in chinese hamster ovary (cho) cells has hindered the development of biologics including hiv vaccines. when expressed in cho cells, the recombinant hiv envelope protein, gp120, undergoes proteolytic clipping by a serine protease at a key epitope recognized by neutralizing antibodies. the problem is particularly acute for envelope proteins from clade b viruses that represent the major genetic subtype circulating in much of the developed w ...201931087560
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
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
four ways to fit an ion channel model.mathematical models of ionic currents are used to study the electrophysiology of the heart, brain, gut, and several other organs. increasingly, these models are being used predictively in the clinic, for example, to predict the risks and results of genetic mutations, pharmacological treatments, or surgical procedures. these safety-critical applications depend on accurate characterization of the underlying ionic currents. four different methods can be found in the literature to fit voltage-sensit ...201931493859
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
a role for alternative end-joining factors in homologous recombination and genome editing in chinese hamster ovary cells.crispr technologies greatly foster genome editing in mammalian cells through site-directed dna double strand breaks (dsbs). however, precise editing outcomes, as mediated by homologous recombination (hr) repair, are typically infrequent and outnumbered by undesired genome alterations. by using knockdown and overexpression studies in chinese hamster ovary (cho) cells as well as characterizing repaired dna junctions, we found that efficient hr-mediated genome editing depends on alternative end-joi ...201931476574
impacts of intentional mycoplasma contamination on cho cell bioreactor cultures.mycoplasma contamination events in biomanufacturing facilities can result in loss of production and costly cleanups. mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and may penetrate the 0.2 µm filters often used in the primary clarification of harvested cell culture fluid. culture cell-based and indicator cell-based assays that are used to detect mycoplasma are highly sensitive but can take up to 28 days to complete and cannot be used for real-time deci ...201931478189
at1aa (angiotensin ii type-1 receptor autoantibodies): cause or consequence of human primary aldosteronism?at1aa (angiotensin ii type-1 receptor autoantibodies) were first detected in patients with primary aldosteronism (pa) because of aldosterone-producing adenoma (apa) with an in-house developed assay, but it remained unclear if they can be ascertained also with commercially available assays and if they have a functional role. aims of our study were to investigate if (1) commercially available kits allow detection of raised at1aa titer in apa; (2) this titer is normalized by adrenalectomy; and (3) ...201931476908
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
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
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
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
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
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
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
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
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
dynamics of mechanosensitive nascent adhesion formation.cellular migration is a tightly regulated process that involves actin cytoskeleton, adaptor proteins, and integrin receptors. forces are transmitted extracellularly through protein complexes of these molecules, called adhesions. adhesions anchor the cell to its substrate, allowing it to migrate. in chinese hamster ovary cells, three classes of adhesion can be identified: nascent adhesions (nas), focal complexes, and focal adhesions, ranked here ascendingly based on size and stability. to underst ...201931493858
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
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
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
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