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kinetic modeling of chinese hamster ovary cell culture: factors and principles.as a host for therapeutic protein expression, chinese hamster ovary (cho) cells are widely utilized in the mainstream biopharmaceutical industry. cell culture process development plays an important role in transitioning laboratory research to manufacturing. among different mathematic tools, kinetic modeling is commonly achieved through analyzing cell culture data to design process parameters, optimize media, and scale up bioreactors. in this review, we examine key factors for upstream process de ...202031928250
targeted optical imaging of the glucagonlike peptide 1 receptor using exendin-4-irdye 800cw.the treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (chi) is surgery. however, intraoperative detection can be challenging. this challenge could be overcome with intraoperative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. here, a novel method for targeted near-infrared (nir) fluorescence imaging of glucagonlike peptide 1 receptor (glp-1r)-positive lesions, using the glp-1 agonist exendin-4 labeled with irdye 8 ...202031924726
different localization of lysosomal-associated membrane protein 1 (lamp1) in mammalian cultured cell lines.lysosomal-associated membrane protein 1 (lamp1) mainly localizes to lysosomes and late endosomes. we herein investigated the intracellular localization of lysosomal membrane proteins in five mammalian cultured cell lines. rat lamp1 fused to enhanced green fluorescent protein (egfp) mostly accumulated at a particular cytoplasmic area and barely co-localized with lysotracker® red dnd-99 in golden hamster kidney bhk-21 cells and chinese hamster ovary cho-k1 cells. golden hamster, chinese hamster, a ...202031907597
choice of host cell line is essential for the functional glycosylation of the fc region of human igg1 inhibitors of influenza b viruses.abs are glycoproteins that carry a conserved n-linked carbohydrate attached to the fc whose presence and fine structure profoundly impacts on their in vivo immunogenicity, pharmacokinetics, and functional attributes. the host cell line used to produce igg plays a major role in this glycosylation, as different systems express different glycosylation enzymes and transporters that contribute to the specificity and heterogeneity of the final igg-fc glycosylation profile. in this study, we compare tw ...202031907284
direct optical detection of cell density and viability of mammalian cells by means of uv/vis spectroscopy.the critical process parameters cell density and viability during mammalian cell cultivation are assessed by uv/vis spectroscopy in combination with multivariate data analytical methods. this direct optical detection technique uses a commercial optical probe to acquire spectra in a label-free way without signal enhancement. for the cultivation, an inverse cultivation protocol is applied, which simulates the exponential growth phase by exponentially replacing cells and metabolites of a growing ch ...202031897554
genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion.in mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. the pathway complexity, however, obfuscates its impact on the secretion of different proteins. unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and chinese hamster ovary cells. the resulting reconstructions enable the c ...202031896772
summation of disinfection by-product cho cell relative toxicity indices: sampling bias, uncertainty, and a path forward.the cyto- and genotoxic potencies of disinfection by-products (dbps) have been evaluated in published literature by measuring the response of exposed chinese hamster ovary cells. in recent publications, dbp concentrations divided by their individual toxicity indices are summed to predict the relative toxicity of a water sample. we hypothesized that the omission or inclusion of certain dbps over others is equivalent to statistical sampling bias and may result in biased conclusions. to test this h ...202031894210
robust analytical methods for the accurate quantification of the total biomass composition of mammalian cells.biomass composition is an important input for genome-scale metabolic models and has a big impact on their predictive capabilities. however, researchers often rely on generic data for biomass composition, e.g. collected from similar organisms. this leads to inaccurate predictions, because biomass composition varies between different cell lines, conditions, and growth phases. in this chapter we present protocols for the determination of the biomass composition of chinese hamster ovary (cho) cells. ...202031893373
small-scale bioreactor supports high density hek293 cell perfusion culture for the production of recombinant erythropoietin.process intensification in mammalian cell culture-based recombinant protein production has been achieved by high cell density perfusion exceeding 108 cells/ml in the recent years. as the majority of therapeutic proteins are produced in chinese hamster ovary (cho) cells, intensified perfusion processes have been mainly developed for this type of host cell line. however, the use of cho cells can result in non-human posttranslational modifications of the protein of interest, which may be disadvanta ...202031891733
cytotoxicity and genotoxicity of dmabee, a co-photoinitiator of resin polymerization, on cho-k1 cells: role of redox and carboxylesterase.the 4-dimethylaminobenzoic acid ethyl ester (dmabee) is an important co-initiator for resin polymerization in dental resinous materials. as a radical forming chemical with high lipophilicity, the genotoxicity and cytotoxicity of dmabee deserve prudent investigation. in this study, we found that dmabee reduced the viability and proliferation of chinese hamster ovary (cho-k1) cells in a dose-dependent manner, and altered cell morphology at higher concentrations. g0/g1 cell cycle arrest was induced ...202031880385
hif-1 signaling pathway implicated in phenotypic instability in a chinese hamster ovary production cell line.monitoring genotypic and phenotypic stability is crucial during the development of recombinant chinese hamster ovary (cho) cell lines. although genotypic instability is well-studied, there are few reports on phenotypic instability. here, a case study of two clonal cell lines derived from pfizer's site-specific integration expression platform that expresses the same monoclonal antibody is described. it is shown that both cell lines (herein referred to as "cell line a" and "cell line b") are genot ...202031872551
contactless electroporation induced by high intensity pulsed electromagnetic fields via distributed nanoelectrodes.pulsed electric fields (pefs) can be used to transiently increase cell membrane permeability in procedures ranging from gene therapy to tumor eradication. although very efficient, pef-based therapies generally require the use of invasive electrodes, which cause pain and tissue damage. an emerging noninvasive, contactless alternative to pefs are high intensity pulsed electromagnetic fields (hi-pemf), whereby the electric field inside the tissue is induced remotely by external pulsed magnetic fiel ...202031869699
acquired glanzmann thrombasthenia associated with platelet desialylation.the notable discrepancy between platelet count and bleeding manifestations in immune thrombocytopenia (itp) patients with acquired glanzmann thrombasthenia (gt) has been described.202031869497
design and synthesis of novel ferrocene-quinoline conjugates and evaluation of their electrochemical and antiplasmodium properties.the tropical disease malaria is responsible for more than 400,000 deaths annually, especially in southeast asia and africa. although the number of malaria cases is declining, there still is an urgent need for novel antimalarial agents. the emergence of hybrid antimalarial agents and the precedence set by the antimalarial drug ferroquine (fq) prompted us to design new ferrocene-containing quinoline structures. herein, we report the efficient synthesis of three different series of ferrocene-quinol ...202031865015
investigating toxicity of urban road deposited sediments using chinese hamster ovary cells and chlorella pyrenoidosa.road deposited sediments (rds) is the key carrier of pollutants in the urban road stormwater processes and hence has been seen as an important pollutant source of urban road stormwater. although many research studies have focused on rds and pollutants attached to rds, the investigation on rds toxicity is very limited. toxicity test can permit an overall assessment on whether the rds polluted stormwater can be safely reused. this paper used two living organisms, namely chinese hamster ovary (cho) ...202031864047
how to produce mabs in a cube-shaped stirred single-use bioreactor at 200 l scale.single-use bioreactors have increasingly been used in recent years, for both research and development as well as industrial production, especially in mammalian cell-based processes. among the numerous single-use bioreactors available today, wave-mixed bags and stirred systems dominate. wave-mixed single-use bioreactors are the system of choice for inoculum production, while stirred single-use bioreactors are most often preferred for antibody expression. for this reason, the present chapter descr ...202031858468
orbitally shaken single-use bioreactor for animal cell cultivation: fed-batch and perfusion mode.increasing the cultivation volume from small to large scale can be a rather complex and challenging process when the method of aeration and mixing is different between scales. orbitally shaken bioreactors (osbs) utilize the same hydrodynamic principles that define the success of smaller-scale cultures, which are developed on an orbitally shaken platform, and can simplify scale-up. here we describe the basic working principles of scale-up in terms of the volumetric oxygen transfer coefficient (kl ...202031858465
using a parallel micro-cultivation system (micro-matrix) as a process development tool for cell culture applications.micro-bioreactors appear frequently in today's biotechnology industry as screening and process development tools for cell culture applications. the micro-bioreactor's small volume allows for a high throughput, and when compared to other small-scale systems, such as microtiter plates, its measurement and control capabilities offer a much better insight into the bioprocess. applikon's micro-matrix is one of the micro-bioreactors that are commercially available today. the micro-matrix system consis ...202031858463
reinvestigation of disulfide-bonded oligomeric forms of the unfolded protein response transducer atf6.atf6α is an endoplasmic reticulum (er)-embedded transcription factor which is rapidly activated by er stress, and a major regulator of er chaperone levels in vertebrates. we previously suggested that atf6α occurs as a monomer, dimer and oligomer in the unstressed er of chinese hamster ovary cells due to the presence of two evolutionarily conserved cysteine residues in its luminal region (c467 and c618), and showed that atf6α is reduced upon er stress, such that only reduced monomer atf6α is tran ...202031852864
biallelic loss-of-function mutations in jam2 cause primary familial brain calcification.primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. currently, four autosomal dominant (slc20a2, pdgfrb, pdgfb, xpr1) and one autosomal recessive (myorg) causative genes have been identified. compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with ...202031851307
investigation and circumvention of transfection inhibition by ferric ammonium citrate in serum-free media for chinese hamster ovary cells.while reliable transfection methods are essential for chinese hamster ovary (cho) cell line engineering, reduced transfection efficiencies have been observed in several commercially prepared media. in this study, we aimed to assess common media additives that impede efficiency mediated by three chemical transfection agents: liposomal-based (lipofectamine 2000), polymer-based (transit-x2), and lipopolyplex-based (transit-pro). an in-house gfp-expressing vector and serum-free medium (bcr-f12: deve ...202031850663
insights into virus inactivation by polysorbate 80 in the absence of solvent.triton x-100 has long been used either alone or in combination with solvent to inactivate enveloped viruses in biopharmaceutical manufacturing. however, european chemicals agency (echa) officially placed triton x-100 on the annex xiv authorization list in 2017 because 4-(1,1,3,3-tetramethylbutyl) phenol, a degradation product of triton x-100, is of harmful endocrine disrupting activities. as a result, any use of triton x-100 in the european economic area would require an echa issued authorizatio ...202031846227
endothelial intercellular cell adhesion molecule 1 contributes to cell aggregate formation in cho cells cultured in serum-free media.chinese hamster ovary (cho) cells have been adapted to grow in serum-free media and in suspension culture to facilitate manufacturing needs. some cho cell lines, however, tend to form cell aggregates while being cultured in suspension. this can result in reduced viability and capacity for single cell cloning (scc) via limiting dilution, and process steps to mitigate cell aggregate formation, for example, addition of anti-cell-aggregation agents. in this study, we have identified endothelial inte ...202031846224
surrogates for the removal by ozonation of the cytotoxicity and dna double-strand break effects of wastewater on mammalian cells.effluents from wastewater treatment plants (wwtps) may contain various pollutants with potential toxic effects. ozonation is widely applied to purify wastewater, which may influence the toxicity and water quality indices simultaneously. the main goal of this study was to reveal influence of ozonation on toxicity of wwtp effluents and to find the surrogates for toxicity changes. cytotoxicity and dna double-strand break (dsb) effect of wwtp effluents were measured based on chinese hamster ovary (c ...202031841803
effects of cysteine, asparagine, or glutamine limitations in chinese hamster ovary cell batch and fed-batch cultures.amino acid availability is a key factor that can be controlled to optimize the productivity of fed-batch cultures. to study amino acid limitation effects, a serum-free chemically defined basal medium was formulated to exclude the amino acids that became depleted in batch culture. the effect of limiting glutamine, asparagine, and cysteine on the cell growth, metabolism, antibody productivity, and product glycosylation was investigated in three chinese hamster ovary (cho) cell lines (cho-dxb11, ch ...202031823468
polymorphisms and endometriosis: a systematic review and meta-analyses.endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. it may lead to infertility and non-specific symptoms such as chronic pelvic pain. endometriosis screening and diagnosis are difficult and time-consuming. late diagnosis (with a delay ranging from 3.3 to 10.7 years) is a major problem and may contribute to disease progression and a worse response to treatment once initiated. efficient screening tests might reduce this diagnostic d ...202031821471
oxidative stress-alleviating strategies to improve recombinant protein production in cho cells.large scale biopharmaceutical production of biologics relies on the overexpression of foreign proteins by cells cultivated in stirred tank bioreactors. it is well recognized and documented fact that protein overexpression may impact host cell metabolism and that factors associated with large scale culture, such as the hydrodynamic forces and inhomogeneities within the bioreactors, may promote cellular stress. the metabolic adaptations required to support the high-level expression of recombinant ...202031814104
microrna-504 functions as a tumor suppressor in oral squamous cell carcinoma through inhibiting cell proliferation, migration and invasion by targeting cdk6.microrna (mirna), as tumor suppressor or oncogene, is involved in the regulation of tumor development. however, the role of mirna in human oral squamous cell carcinoma (oscc) is less well understood. in our previous studies, we have successfully established a chinese hamster oral squamous cell carcinoma animal model and constructed a mirna differential expression profile, and screened out the abnormal expressed gene (mir-504). the purpose of this study was to investigate the regulatory mechanism ...202031812760
engineering of chinese hamster ovary cell lipid metabolism results in an expanded er and enhanced recombinant biotherapeutic protein production.chinese hamster ovary (cho) cell expression systems have been exquisitely developed for the production of recombinant biotherapeutics (e.g. standard monoclonal antibodies, mabs) and are able to generate efficacious, multi-domain proteins with human-like post translational modifications at high concentration with appropriate product quality attributes. however, there remains a need for development of new cho cell expression systems able to produce more challenging secretory recombinant biotherape ...202031805379
dr10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.both glucagon-like peptide-1 (glp-1) and glucagon (gcg) belong to the incretin family. this study aimed to investigate the pharmacokinetics and pharmacodynamics of dr10601, a fully recombinant hybrid peptide with dual glp-1/gcg receptor agonistic activity.202031786794
modelling of hollow fiber membrane bioreactor for mammalian cell cultivation using computational hydrodynamics.the hollow fiber membrane bioreactor (hfmb) has been investigated for the cultivation of mammalian chinese hamster ovary cell expansion. the experiments were carried out in petri's dishes and in the hollow fiber membrane bioreactor having 20 fibers (s2025 from fibercell systems). the approach to hfmb modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. the hydrodynamic model is made using ansys fluent software. the mathematical model of hfmb was develop ...202031786664
knockout of sialidase and pro-apoptotic genes in chinese hamster ovary cells enables the production of recombinant human erythropoietin in fed-batch cultures.sialic acid, a terminal monosaccharide present in n-glycans, plays an important role in determining both the in vivo half-life and the therapeutic efficacy of recombinant glycoproteins. low sialylation levels of recombinant human erythropoietin (rhepo) in recombinant chinese hamster ovary (rcho) cell cultures are considered a major obstacle to the production of rhepo in fed-batch mode. this is mainly due to the accumulation of extracellular sialidases released from the cells. to overcome this hu ...202031785386
bioinformatic identification of chinese hamster ovary (cho) cold-shock genes and biological evidence of their cold-inducible promoters.lower cultivation temperature dramatically affects cell growth and cellular productivity in chinese hamster ovary cells (cho) and is often used in industrial applications with the aim to enhance productivity. cold-inducible proteins whose activity is induced at lower temperature play an important role in understanding the mechanisms of cold-induced changes in gene expression. one of these mechanisms is increased transcription of specific target genes controlled by sequence elements in cold-induc ...202031785035
evidence for diversity in the activation of the melanocortin 2 receptor: a study on gar, elephant shark and stingray mc2rs.the melanocortin-2 receptor (mc2r) is a critical component of the hpi and hpa axes of cartilaginous fishes, teleosts and tetrapods. studies on teleost and tetrapod orthologs suggest two contact sites between acth and the receptor involving the following motifs on acth: h6f7r8w9 and k15k16r17r18p19. using spotted gar (g) mc2r as a representative bony fish mc2r ortholog, we found that activation of gmc2r in chinese hamster ovary (cho) cells was diminished following stimulation of the transfected c ...202031778725
engineering of an iranian bordetella pertussis strain producing inactive pertussis toxin.introduction. differences between the genomic and virulence profile of bordetella pertussis circulating strains and vaccine strains are considered as one of the important reasons for the resurgence of whooping cough (pertussis) in the world. genetically inactivated b. pertussis is one of the new strategies to generate live-attenuated vaccines against whooping cough.aim. the aim of this study was to construct a b. pertussis strain based on a predominant profile of circulating iranian isolates tha ...202031778110
distance effect characteristic of the matrix attachment region increases recombinant protein expression in chinese hamster ovary cells.previously, we have found that the matrix attachment region (mar) may confer a 'distance effect' on transgene expression. this work aims to systematically explore the increased transgene expression in transfected chinese hamster ovary (cho) cells due to the characteristics of mar and its mechanism.202031776751
heparin chromatography as an in vitro predictor for antibody clearance rate through pinocytosis.the pharmacokinetic (pk) properties of therapeutic antibodies directly affect efficacy, dose and dose intervals, application route and tissue penetration. in indications where health-care providers and patients can choose between several efficacious and safe therapeutic options, convenience (determined by dosing interval or route of application), which is mainly driven by pk properties, can affect drug selection. therapeutic antibodies can have greatly different pk even if they have identical fc ...202031769731
a novel method based on nonparametric regression with a gaussian kernel algorithm identifies the critical components in cho media and feed optimization.as the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. however, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. therefore, in this work, we developed a nrgk (nonparametric regression with gaussian kernel) method, which aimed to identify the critical components that affect product titres duri ...202031754859
unaccompanied mechanosensory domain mediates low expression of glycoprotein ibα: implications for bernard-soulier syndrome.disruption of protein folding or inter-subunit interactions in the platelet glycoprotein (gp)ib-ix complex leads to its abnormally low expression in the plasma membrane, the hallmark of bernard-soulier syndrome (bss).202031749281
ercc1 c8092a polymorphism predicts fair survival outcome in japanese patients with pharyngo-laryngeal squamous cell carcinoma.to evaluate the prognostic significance of dna excision repair gene polymorphisms, excision repair cross-complementation group 1 (ercc1) and x-ray repair complementing defective repair in chinese hamster cells 1 (xrcc1) polymorphisms were investigated in japanese patients with head and neck squamous cell carcinoma (hnscc).202031749055
developing an equivalent toxicity area approach to comparing toxicity of urban road deposited sediments.urban road stormwater has been seen as an alternative water resource for mitigating water scarcity. road deposited sediments (rds) is the primary source of road stormwater pollution since many toxic pollutants are attached to rds and eventually enter stormwater runoff when rainfall events occur. this could threaten road stormwater reuse safety. this study developed an innovative equivalent toxicity area (eta) approach to comparing overall toxicity of rds among different road sites. in the eta ap ...202031744684
assuring clonality on the beacon digital cell line development platform.during biomanufacturing cell lines development, the generation and screening for single-cell derived subclones using methods that enable assurance of clonal derivation can be resource- and time-intensive. high-throughput miniaturization, automation, and analytic strategies are often employed to reduce such bottlenecks. the beacon platform from berkeley lights offers a strategy to eliminate these limitations through culturing, manipulating, and characterizing cells on custom nanofluidic chips via ...202031743597
resveratrol addition to chinese hamster ovary cell culture media: the effect on cell growth, monoclonal antibody synthesis, and its chemical modification.the effect of the addition of resveratrol to cell culture media during the production of monoclonal antibodies was investigated. treatments of chinese hamster ovary (cho) cells expressing immunoglobulin g (igg) with 25 and 50 μm resveratrol showed that resveratrol was capable of slowing cell growth while almost doubling cell-specific productivity to 4.7 ± 0.6 pg igg/cell·day, resulting in up to a 1.37-fold increase of the final igg titer. a resveratrol concentration of 50 μm slowed the progressi ...202031742929
comparative cytotoxicity of halogenated aromatic dbps and implications of the corresponding developed qsar model to toxicity mechanisms of those dbps: binding interactions between aromatic dbps and catalase play an important role.halogenated aromatic disinfection byproducts (dbps) are a new group of emerging dbps identified recently. they have been detected in disinfected drinking water, wastewater effluents, recreational water and oil/gas produced water, at concentrations of ng/l to μg/l in general. previously studies have demonstrated that most of them can induce developmental toxicity and growth inhibition in aquatic organisms based on in vivo bioassays. in this study, to further understand the adverse effects of arom ...202031739241
human cyp1b1-dependent genotoxicity of dioxin-like polychlorinated biphenyls in mammalian cells.polychlorinated biphenyls (pcbs) are persistent organic pollutants and human carcinogens. it was reported that rat cyp1a1 and catfish cyp1a can hydroxylate 3,3',4,4',5-pentachlorobiphenyl (pcb 126) and 3,3',4,4'-tetrachlorobiphenyl (pcb 77), while potential roles of other cyp1 enzymes in the metabolism of dioxin-like (dl) pcbs remain unconfirmed. in this study, three representative dl-pcbs, i.e., pcb 77, pcb 126, and 3,4,4',5-tetrachlorobiphenyl (pcb 81), were investigated on their genotoxicity ...202031733235
role of a new bioassay for thyroid-stimulating antibodies (aequorin tsab) in graves' ophthalmopathy.graves' ophthalmopathy (go) is characterized by an autoimmune reaction against thyrotropin (tsh) receptors and is diagnosed by tsh receptor antibody (trab). a novel assay for thyroid-stimulating antibody (tsab) was recently introduced using a frozen chinese hamster ovary cell line expressing tsh receptors, cyclic adenosine monophosphate (camp)-gated calcium channel, and aequorin (aequorin tsab). the aim of this study was to evaluate the role of aequorin tsab in go. we studied 136 japanese patien ...202031827052
an agonist radioligand for the proinflammatory lipid-activated g protein-coupled receptor gpr84 providing structural insights.the orphan g protein-coupled receptor (gpcr) gpr84 is expressed on immune cells mediating proinflammatory and immunostimulatory effects. in this study, we prepared the fully efficacious, nonbiased gpr84 agonist 6-hexylamino-2,4(1h,3h)-pyrimidinedione (6) in tritium-labeled form ([3h]psb-1584) by hydrogenation of a hexenyl-substituted precursor with tritium gas. the radioligand was characterized by kinetic, saturation, and competition assays using membranes of chinese hamster ovary cells recombin ...202031721581
an easy and fast method for production of chinese hamster ovary cell line expressing and secreting human recombinant activin a.growth factors are key elements of embryonic stem cell (esc) research. cell line development in eukaryotes is a time-consuming procedure which usually takes 12-18 months. here, we report an easy and fast method with which production of chinese hamster ovary (cho) cells that express and secrete recombinant activin a, as a major growth factor in endo/mesoderm differentiation of embryonic stem cells is achieved within 3-4 weeks.202031721527
aqueous extract of forsythia viridissima fruits: acute oral toxicity and genotoxicity studies.forsythia viridissima fruit, one of forsythiae fructus (ff) is widely used in traditional medicine to treat diverse diseases-related clinical symptoms, including fever, pain, vomiting, nausea, and abscess. however, the safety of ff has not been fully assessed.202031715286
chlorinated effluent organic matter causes higher toxicity than chlorinated natural organic matter by inducing more intracellular reactive oxygen species.during unplanned indirect potable reuse, treated wastewater that contains effluent organic matter (eom) enters the drinking water source, resulting in different toxicity from natural organic matter (nom) in surface water during chlorination. this study found that, during chlorination, eom formed more total organic halogen (tox) and highly toxic nitrogenous disinfection byproducts (dbps) like dichloroacetonitrile and trichloronitromethane than nom did. oxidative stress including both reactive oxy ...202031710900
cardiotoxic effects of [3-[2-(diethylamino)ethyl]-1h-indol-4-yl] acetate and 3-[2-[ethyl(methyl)amino]ethyl]-1h-indol-4-ol.two synthetic tryptamines, namely [3-[2-(diethylamino)ethyl]-1h-indol-4-yl] acetate (4-aco-det) and 3-[2-[ethyl(methyl)amino]ethyl]-1h-indol-4-ol (4-ho-met), are abused by individuals seeking recreational hallucinogens. these new psychoactive substances (npss) can cause serious health problems because their adverse effects are mostly unknown. in the present study, we evaluated the cardiotoxicity of 4-aco-det and 4-ho-met using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt ...202031706004
a high yielding ifnar1 ecd mammalian expression process for use in autoimmune disease drug development.interferon-alpha receptor 1 (ifnar1) is a target of interest for recombinant biotherapeutics that block the jak/stat pathway. this pathway is believed to play a role in many diseases including hepatitis b and c, herpes simplex, multiple sclerosis, and other autoimmune disorders. by using ifnar1 as a target to block type i ifn from binding to the jak/stat pathway and prevent activation of this target, autoimmune disease progression can be modulated. current ifnar1 extracellular domain (ecd) expre ...202031689498
targeted capture of chinese hamster ovary host cell proteins: peptide ligand binding by proteomic analysis.the clearance of host cell proteins (hcps) is of crucial importance in biomanufacturing, given their diversity in composition, structure, abundance, and occasional structural homology with the product. the current approach to hcp clearance in the manufacturing of monoclonal antibodies (mabs) relies on product capture with protein a followed by removal of residual hcps in flow-through mode using ion exchange or mixed-mode chromatography. recent studies have highlighted the presence of "problemati ...202031654407
a critical assessment of the genotoxicity profile of the fungicide tricyclazole.tricyclazole (8-methyl-[1,2,4]triazolo[3,4-b][1,3]benzothiazole) is a fungicide used globally on rice for treatment of the seasonal rice blast disease. human exposure to this fungicide can occur via dietary and nondietary routes. in a battery of in vitro assays, tricyclazole did not induce gene mutations in bacteria (ames test) or at the hprt locus of cho cells. it was also negative for the induction of micronuclei in human lymphocyte cultures and unscheduled dna synthesis (uds) in primary rat h ...202031633836
unraveling what makes a monoclonal antibody difficult-to-express: from intracellular accumulation to incomplete folding and degradation via erad.although most therapeutic monoclonal antibodies (mabs) can routinely be produced in the multigram per litre range, some mab candidates turn out to be difficult-to-express (dte). in addition, the class of more complex biological formats is permanently increasing and mammalian expression systems like chinese hamster ovary (cho) cell lines can show low performance. hence, there is an urgent need to identify any rate limiting processing step during cellular synthesis. therefore, we assessed the intr ...202031631329
characterization and mutagenesis of chinese hamster ovary cells endogenous retroviruses to inactivate viral particle release.the chinese hamster ovary (cho) cells used to produce biopharmaceutical proteins are known to contain type-c endogenous retrovirus (erv) sequences in their genome and to release retroviral-like particles. although evidence for their infectivity is missing, this has raised safety concerns. as the genomic origin of these particles remained unclear, we characterized type-c erv elements at the genome, transcriptome, and viral particle rna levels. we identified 173 type-c erv sequences clustering int ...202031631325
awakening dormant glycosyltransferases in cho cells with crispra.chinese hamster ovary (cho) cells are the preferred workhorse for the biopharmaceutical industry, and crispr/cas9 has proven powerful for generating targeted gene perturbations in cho cells. here, we expand the crispr engineering toolbox with crispr activation (crispra) to increase transcription of endogenous genes. we successfully increased transcription of mgat3 and st6gal1, and verified their activity on a functional level by subsequently detecting that the appropriate glycan structures were ...202031631317
ivabradine for chronic heart rate control in persistent atrial fibrillation. design of the brake-af project.ivabradine is an inhibitor of the if channel, the main determinant of the pacemaker function of the sinus node. the drug has been approved for the treatment of angina and heart failure. there is some evidence of its role as an inhibitor of atrial-ventricular node (avn) conduction. the aim of the brake-af project is to assess ivabradine use for rate control in atrial fibrillation (af).202031631048
engineering antibodies on the surface of cho cells.while antibody libraries are traditionally screened in phage, bacterial, or yeast display formats, they are produced in large scale for pharmaceutical and commercial use in mammalian cell lines. the simpler organisms used for screening have significantly different folding and glycosylation machinery than mammalian cells; consequently, clones resulting from these libraries may require further optimization for mammalian cell expression. to streamline the antibody discovery process, we developed a ...202031625108
impact of micro and macroporous tff membranes on product sieving and chromatography loading for perfusion cell culture.bioprocess intensification can be achieved through high cell density perfusion cell culture with continuous protein capture integration. protein passage and cell retention are commonly accomplished using tangential flow filtration systems consisting of microporous membranes. significant challenges, including low efficiency and decaying product sieving over time, are commonly observed in these cell retention devices. here, we demonstrate that a macroporous membrane overcomes the product sieving c ...202031612989
understanding the mechanism of copurification of "difficult to remove" host cell proteins in rituximab biosimilar products.host cell proteins (hcps) are considered a critical quality attribute and are linked to safety and efficacy of biotherapeutic products. researchers have identified 10 hcps in chinese hamster ovary (cho) that exhibit common characteristics of product association, coelution, and age-dependent expression and therefore are "difficult to remove" during downstream purification. these include cathepsin d, clusterin, galectin-3-binding protein, g-protein coupled receptor 56, lipoprotein lipase, metallop ...202031661608
effects of different 2a peptides on transgene expression mediated by tricistronic vectors in transfected cho cells.multicistronic vectors can increase transgene expression and decrease the imbalance of gene expression in the chinese hamster ovary (cho) cell expression system. small, self-cleaving 2a peptides have a high cleavage efficiency and are essential for constructing high-expression multicistronic vectors. in this study, we investigated the effects of two different 2a peptides on transgene expression in cho cells via their mediating action on tricistronic vectors. the enhanced green fluorescent protei ...202031659692
integration of high-throughput analytics and cell imaging enables direct early productivity and product quality assessment during chinese hamster ovary cell line development for a complex multi-subunit vaccine antigen.mammalian cell line generation typically includes stable pool generation, single cell cloning and several rounds of clone selection based on cell growth, productivity and product quality criteria. individual clone expansion and phenotype-based ranking is performed initially for hundreds or thousands of mini-scale cultures, representing the major operational challenge during cell line development. automated cell culture and analytics systems have been developed to enable high complexity clone sel ...202031568688
the impact of sialylation linkage-type on the pharmacokinetics of recombinant butyrylcholinesterases.chinese hamster ovary (cho) cells typically produce glycoproteins with n-glycans terminating in α-2,3 sialylation. human cells produce glycoproteins that include α-2,3 and α-2,6 sialic acids. to examine the impact of altering protein sialylation on pharmacokinetic properties, recombinant human butyrylcholinesterase (bche) was produced in cho cells by knocking out the α-2,3 sialyltransferase genes followed by overexpression of the α-2,6 sialyltransferase (26bche) enzyme. the n-glycan composition ...202031544955
glycan residues balance analysis - greba: a novel model for the n-linked glycosylation of igg produced by cho cells.the structure of n-linked glycosylation is a very important quality attribute for therapeutic monoclonal antibodies. different carbon sources in cell culture media, such as mannose and galactose, have been reported to have different influences on the glycosylation patterns. accurate prediction and control of the glycosylation profile are important for the process development of mammalian cell cultures. in this study, a mathematical model, that we named glycan residues balance analysis (greba), w ...202031539564
advancing biologics development programs with legacy cell lines: advantages and limitations of genetic testing for addressing clonality concerns prior to availability of late stage process and product consistency data.the bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. to ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few ye ...202031519780
identification of novel phytocannabinoids from ganoderma by label-free dynamic mass redistribution assay.located throughout the body, cannabinoid receptors (cb1 and cb2) are therapeutic targets for obesity/metabolic diseases, neurological/mental disorders, and immune modulation. phytocannabinoids are greatly important for the development of new medicines with high efficacy and/or minor side effects. plants and fungi are used in traditional medicine for beneficial effects to mental and immune system. the current research studied five fungi from the genus ganoderma and five plants: ganoderma hainanen ...202031494202
hplc-esi-qqq based standardization, mutagenic and genotoxic potential of methanol extract of ziziphus mauritiana lam leaves.the leaves of ziziphus mauritiana lam have been an integral part of the traditional system of medicine for the treatment of inflammation, wounds, fever, asthma and liver disorders. the leaves are utilised as an edible vegetable in rural parts of india and indonesia. despite its pharmacological significance, ziziphus mauritiana lam lacks scientific evidence on its mutagenic and genotoxic potential.202031493461
role of human n-acetyltransferase 2 genetic polymorphism on aromatic amine carcinogen-induced dna damage and mutagenicity in a chinese hamster ovary cell mutation assay.carcinogenic aromatic amines such as 4-aminobiphenyl (abp) and 2-aminofluorene (af) require metabolic activation to form electrophilic intermediates that mutate dna leading to carcinogenesis. bioactivation of these carcinogens includes n-hydroxylation catalyzed by cyp1a2 followed by o-acetylation catalyzed by arylamine n-acetyltransferase 2 (nat2). to better understand the role of nat2 genetic polymorphism in abp- and af-induced mutagenesis and dna damage, nucleotide excision repair-deficient (u ...202031490564
intracerebroventricular enzyme replacement therapy with β-galactosidase reverses brain pathologies due to gm1 gangliosidosis in mice.autosomal recessive mutations in the galactosidase β1 (glb1) gene cause lysosomal β-gal deficiency, resulting in accumulation of galactose-containing substrates and onset of the progressive and fatal neurodegenerative lysosomal storage disease, gm1 gangliosidosis. here, an enzyme replacement therapy (ert) approach in fibroblasts from gm1 gangliosidosis patients with recombinant human β-gal (rhβ-gal) produced in chinese hamster ovary cells enabled direct and precise rhβ-gal delivery to acidified ...202031481471
phosphorylation of unique c-terminal sites of the mu-opioid receptor variants 1b2 and 1c1 influences their gs association following chronic morphine.we recently demonstrated in rat spinal cord that a regimen of escalating doses of systemic morphine, analogous to regimens used clinically for chronic pain management, selectively up-regulates the mu-opioid receptor (mor) splice variants mor-1b2 and mor-1c1 mrna and functional protein. this study investigated the potential relevance of up-regulating mor-1b2 and mor-1c1 to the ability of chronic morphine to shift mor signaling from predominantly gi /go inhibitory to gs stimulatory. specifically, ...202031479519
mrna transfection into cho-cells reveals production bottlenecks.obtaining highly productive chinese hamster ovary (cho)-cell clones for the production of therapeutic proteins relies on multiple time-consuming selection steps. several cho-cell strains with high degrees of genomic and epigenetic variation are available. each harbor potential advantages and disadvantages for any given product, particularly those considered difficult to express. a simple test system to quickly assess compatibility of cell line and product may therefore prove useful. transient pl ...202031475780
process intensification in fed-batch production bioreactors using non-perfusion seed cultures.although process intensification by continuous operation has been successfully applied in the chemical industry, the biopharmaceutical industry primarily uses fed-batch, rather than continuous or perfusion methods, to produce stable monoclonal antibodies (mabs) from chinese hamster ovary (cho) cells. conventional fed-batch bioreactors may start with an inoculation viable cell density (vcd) of ~0.5 × 106 cells/ml. increasing the inoculation vcd in the fed-batch production bioreactor (referred to ...202031379298
characterization of chinese hamster ovary cells with disparate chromosome numbers: reduction of the amount of mrna relative to total protein.chromosomes in chinese hamster ovary (cho) cells are labile. we have shown that high-chromosome-number cho cells have greater potential to become robust producers of recombinant proteins. one explanation being the increase in transgene integration sites. however, high-chromosome-number cell clones produce more igg3 following culture of single-cell clones, even under conditions that yield the same number of integrations as cells with normal chromosome numbers. here, we characterized high-chromoso ...202031303495
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
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