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identification of a new cell-penetrating peptide derived from the african swine fever virus cd2v protein.the african swine fever virus (asfv) is a huge and complex dna virus that can lead to the acute death of pigs and cause huge losses to the global swine industry. the cd2v protein is a transmembrane protein encoded by the asfv's ep402r gene, which can effectively inhibit the bystander lymphocyte proliferation in response to mitogens and mediate the absorption of red blood cells to asfv-infected cells. the cd2v protein contains repetitive amino acid sequences ([kpcppp]3 labeled as raas), which is ...202134006158
the cryo-em structure of vesivirus 2117 highlights functional variations in entry pathways for viruses in different clades of the vesivirus genus.vesivirus 2117 is an adventitious agent that has been responsible for lost productivity in biopharmaceutical production following contamination of chinese hamster ovary cell cultures in commercial bioreactors. a member of the caliciviridae, 2117 is classified within the vesivirus genus in a clade that includes canine and mink caliciviruses but is distinct from the vesicular exanthema of swine virus (vesv) clade, which includes the extensively studied feline calicivirus (fcv). we have used cryoge ...202133853966
structural and functional characterization of sars-cov-2 rbd domains produced in mammalian cells.as the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic is still ongoing and dramatically influences our life, the need for recombinant viral proteins for diagnostics, vaccine development, and research is very high. the spike (s) protein, and particularly its receptor-binding domain (rbd), mediates the interaction with the angiotensin-converting enzyme 2 (ace2) receptor on host cells and may be modulated by its structural features. therefore, well-characterized recombinant r ...202133871970
preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) continue at pace. here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (s) protein, sclamp, in combination with the licensed adjuvant mf59 'mf59c.1' (seqirus, parkville, australia).202133841880
development of a colloidal gold-based immunochromatographic strip for rapid detection of severe acute respiratory syndrome coronavirus 2 spike protein.the outbreak and worldwide pandemic of the novel severe acute respiratory syndrome coronavirus 2 (sars-cov-2) have a significant impact on global economy and human health. in order to reduce the disease spread, 16 monoclonal antibodies (mcabs) again sars-cov-2 were generated by immunized mice with the spike protein receptor binding domain (rbd), which was expressed in chinese hamster ovary cell (cho). a colloidal gold-based immunochromatographic strip was developed with two mcabs to detect sars- ...202133777026
high-level expression of the monomeric sars-cov-2 s protein rbd 320-537 in stably transfected cho cells by the eef1a1-based plasmid vector.the spike (s) protein is one of the three proteins forming the coronaviruses' viral envelope. the s protein of the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has a spatial structure similar to the s proteins of other mammalian coronaviruses, except for a unique receptor-binding domain (rbd), which is a significant inducer of host immune response. recombinant sars-cov-2 rbd is widely used as a highly specific minimal antigen for serological tests. correct exposure of antigenic d ...202133529230
previously published ethno-pharmacological reports reveal the potentiality of plants and plant-derived products used as traditional home remedies by bangladeshi covid-19 patients to combat sars-cov-2.several plants have traditionally been used since antiquity to treat various gastroenteritis and respiratory symptoms similar to covid-19 outcomes. the common symptoms of covid-19 include fever or chills, cold, cough, flu, headache, diarrhoea, tiredness/fatigue, sore throat, loss of taste or smell, asthma, shortness of breath, or difficulty breathing, etc. this study aims to find out the plants and plant-derived products which are being used by the covid-19 infected patients in bangladesh and ho ...202134305428
production of monoclonal antibodies targeting aminopeptidase n in the porcine intestinal mucosal epithelium.porcine aminopeptidase n (apn), a membrane-bound metallopeptidase abundantly present in small intestinal mucosa, can initiate a mucosal immune response without any interference such as low protein expression, enzyme inactivity, or structural changes. this makes apn an attractive candidate in the development of vaccines that selectively target the mucosal epithelium. previous studies have shown that apn is a receptor protein for both enterotoxigenic escherichia coli (e. coli) f4 and transmissible ...202134096912
immunogenicity and safety of hepatitis b vaccination in patients with type 2 diabetes in china: an open-label randomized controlled trial.hepatitis b virus (hbv) infection remains a global public health challenge. patients with diabetes are at greater risk of hbv infection than healthy people. the immunogenicity and safety of two major hepatitis b vaccines were evaluated in chinese patients with diabetes.202133992438
culture media optimization for chinese hamster ovary cell growth and expression of recombinant varicella-zoster virus glycoprotein e.herpes zoster (hz) is caused by reactivation of varicella-zoster virus (vzv) latent in the sensory ganglia and causes severe pain, often leading to postherpetic neuralgia (phn). two prophylactic vaccines against hz are currently licensed for human use, a live attenuated vaccine and a subunit vaccine containing recombinant vzv glycoprotein e (ge) as antigen. the latter has superior protective efficacy against hz and phn. during hz subunit vaccine development, we obtained chinese hamster ovary (ch ...202133897103
efficacy of minute virus of mice (mvm) inactivation utilizing high temperature short time (htst) pasteurization and suitability assessment of pasteurized, concentrated glucose feeds in chinese hamster ovary (cho) cell expression systems.there is a growing need to provide effective adventitious agent mitigation for high risk upstream cell culture raw materials used for the production of biologics. it is also highly important in the growing fields of cell and gene therapies. glucose is a critical raw material necessary for effective cell growth and productivity; however, glucose is the highest risk animal-origin-free raw material for viral contamination, and often the highest risk raw material in the upstream process as more comp ...202134257631
development of anti-human t cell immunoreceptor with ig and itim domains (tigit) monoclonal antibodies for flow cytometry.immune checkpoint inhibitors targeting programmed cell death-ligand 1 (pd-l1), programmed cell death-1 (pd-1), and cytotoxic t lymphocyte-associated antigen 4 (ctla-4) recently made a significant survival rate improvement in cancer treatment. t cell immunoreceptor with ig and itim domains (tigit) is expressed in t and nk cells related to their activities. it has a single extracellular immunoglobulin domain, a type 1 transmembrane domain, and a single intracellular itim. tigit binds with poliovir ...202133900817
culturing chinese hamster ovary cells on cyclo olefin polymer triggers epithelial-mesenchymal transition and spheroid formation, which increases the foreign gene expression driven by the moloney murine leukemia virus long terminal repeat promoter.chinese hamster ovary (cho) cells are frequently used for recombinant protein production (rpp) as a host. while the rpp has been proven successful, there is still a compelling need for further improvement. cyclo olefin polymer (cop) is a plastic material widely utilized due to its properties including its low protein absorption. we applied this as a raw material for rpp cell culture to see if the cop is suitable. a recombinant cho cell line expressing the human erythropoietin (hepo) gene under t ...202133913259
early detection of severe acute respiratory syndrome coronavirus 2 antibodies as a serologic marker of infection in patients with coronavirus disease 2019.thousands of medical staff have been infected with severe acute respiratory syndrome coronavirus 2 (sars-cov-2), with hundreds of deaths reported. such loss could be prevented if there were a serologic assay for sars-cov-2-specific antibodies for serological surveillance of its infection at the early stage of disease.202032357209
the development and study of recombinant immunoglobulin a to hemagglutinins of the influenza virus.we obtained recombinant variants of human antibody fi6 broadly specific to hemagglutinins of the influenza a virus. on the basis of a bi-promoter (cmv, hef1-htlv) vector, we developed genetic constructs for the expression of the heavy and light chains of the immunoglobulins of iga1-, iga2m1-, and igg-isotypes. following transfection and selection, stable chinese hamster ovary (cho) cell lines were produced. the antibodies of iga1-, iga2m1-, and igg-isotypes were purified from culture media. we p ...202030116613
assessment of complex genomic alterations induced by azt, 3tc, and the combination azt +3tc.highly active antiretroviral therapy (haart) regimens are based on the use of nucleoside reverse transcriptase inhibitors (nrtis), which are the main drugs used by patients infected with the human immunodeficiency virus (hiv). the use of nrtis combinations has afforded clear clinical benefits to patients undergoing haart. however, the combination of two nrtis may increase the risk of genomic instability in comparison with the drugs administered individually. we analyzed the ability of zidovudine ...202030208744
a highly productive cho cell line secreting human blood clotting factor ix.hemophilia b patients suffer from an inherited blood-clotting defect and require regular administration of blood-clotting factor ix replacement therapy. recombinant human factor ix produced in cultured cho cells is nearly identical to natural, plasma-derived factor ix and is widely used in clinical practice. development of a biosimilar recombinant human factor ix for medical applications requires the generation of a clonal cell line with the highest specific productivity possible and a high leve ...202029713519
development and characterization of anti-sheep podoplanin monoclonal antibodies pmab-253 and pmab-260.anti-podoplanin (pdpn) monoclonal antibodies (mabs) are needed as markers for lymphatic endothelial cells or type i alveolar cells in immunohistochemical analyses. we have developed anti-pdpn mabs for many species, including humans, mice, rats, rabbits, dogs, cats, bovines, pigs, tasmanian devils, alpacas, tigers, whales, goats, horses, and bears. this study develops and characterizes anti-sheep pdpn (spdpn) mabs using cell-based immunization and screening (cbis) method. a rap14 tag was added to ...202032679010
development of an anti-sheep podoplanin monoclonal antibody pmab-256 for immunohistochemical analysis of lymphatic endothelial cells.sensitive and specific monoclonal antibodies (mabs) targeting podoplanin (pdpn) are needed for immunohistochemical analyses as a marker for lymphatic endothelial cells. we recently have developed anti-pdpn mabs against many species, including human, mouse, rat, rabbit, dog, cat, bovine, pig, tasmanian devil, alpaca, tiger, whale, goat, horse, and bear. however, anti-sheep pdpn (spdpn) has not yet been established. in this study, we used the cell-based immunization and screening method for the de ...202032349619
osmolality as a lever to modulate the n-glycolylneuraminicacid (neu5gc) level of a recombinant glycoprotein produced in chinese hamster ovary cells.glycoproteins could be highly sialylated, and controlling the sialic acid levels for some therapeutic proteins is critical to ensure product consistency and efficacy. n-acetylneuraminic acid (neu5ac, or nana) and n-glycolylneuraminic acid (neu5gc, or ngna) are the two most common forms of sialic acids produced in mammalian cells. as neu5gc is not produced in humans and can elicit immune responses, minimizing neu5gc formation is important in controlling this quality attribute for complex glycopro ...202032542945
high throughput generation of a resource of the human secretome in mammalian cells.the proteins secreted by human tissues and blood cells, the secretome, are important both for the basic understanding of human biology and for identification of potential targets for future diagnosis and therapy. here, a high-throughput mammalian cell factory is presented that was established to create a resource of recombinant full-length proteins covering the majority of those annotated as 'secreted' in humans. the full-length dna sequences of each of the predicted secreted proteins were gener ...202032502629
vanadium: risks and possible benefits in the light of a comprehensive overview of its pharmacotoxicological mechanisms and multi-applications with a summary of further research trends.vanadium (v) is an element with a wide range of effects on the mammalian organism. the ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine.202032305626
lack of acute toxicity and mutagenicity from recombinant epinephelus lanceolatus piscidin expressed in pichia pastoris.the antimicrobial peptide (amp) piscidin was identified from epinephelus lanceolatus and demonstrated to possess antimicrobial and immune-related functions. supplementation of feed with recombinant epinephelus lanceolatus piscidin (rep)-expressing yeast pellets may minimize the excessive use of antibiotics and control pathogens in aquaculture or animal husbandry. however, before implementing rep as a supplement, it is necessary to understand whether it harbors any toxicity. since toxicological i ...202032290449
gene (hprt) and chromosomal (mn) mutations of nickel metal powder in v79 chinese hamster cells.nickel metal is a naturally occurring element used in many industrial and consumer applications. human epidemiological data and animal cancer bioassays indicate that nickel metal is not likely to be a human carcinogen. yet, nickel metal is classified as a suspected human carcinogen (clp) and possibly carcinogenic to humans (iarc). there are no reliable studies on the potential for nickel metal to induce gene and micronucleus (mn) mutations. to fill these datagaps and increase our understanding o ...202032014793
hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants.a recombinant respiratory syncytial virus (rsv) fusion glycoprotein candidate vaccine (rsv-pref) manufactured in chinese hamster ovary cells was developed for immunization of pregnant women, to protect newborns against rsv disease through trans-placental antibody transfer. traces of a host-cell protein, hamster neogenin (haneo1), were identified in purified rsv-pref antigen material. given the high amino-acid sequence homology between haneo1 and human neogenin (huneo1), there was a risk that pot ...202031951765
towards a new avenue for producing therapeutic proteins: microalgae as a tempting green biofactory.most of the recent approved therapeutic proteins are multi-subunit biologics, which need glycosylation and disulfide bridges for their correct conformation and biological functions. currently, there exist many protein-based drugs that are mostly produced in the chinese hamster ovary (cho) cells. however, this expression system appears to associate with some limitations both in upstream and downstream processing steps, including low growth rate, sensitivity to different stresses and pathogens, an ...202031862234
toxicity variability of urban road stormwater during storage processes in shenzhen, china: identification of primary toxicity contributors and implications for reuse safety.urban road stormwater reuse is one of the most important ways to mitigate water resource shortage. generally, stormwater is stored prior to reuse or further treatment. this study explored the stormwater toxicity variability during two types of storages, closed and open storages using chinese hamster ovary cells (cho), which are mammalian cells. the toxicity test by cho cells can indirectly represent the risk related to human health. both rainfall (without reaching ground surfaces) and urban road ...202032717603
novel peptide ligands for antibody purification provide superior clearance of host cell protein impurities.the quest for ligands alternative to protein a for the purification of monoclonal antibodies (mabs) has been pursued for almost three decades. yet, the igg-binding peptides known to date still fall short of the host cell protein (hcp) logarithmic removal value (lrv) set by protein a media (2.5-3.1). in this study, we present an integrated computational-experimental approach leading to the discovery of peptide ligands that provide hcp lrvs on par with protein a. first, the screening of 60,000 pep ...202032709313
chromatographic clarification overcomes chromatin-mediated hitch-hiking interactions on protein a capture column.protein a capture chromatography is a critical unit operation in the clearance of host cell protein (hcp) impurities in monoclonal antibody (mab) purification processes. though one of the most effective purification steps, variable levels of protein impurities are often observed in the eluate. coelution of hcp impurities is suggested to be strongly affected by the presence of chromatin complexes (gagnon et al., 2014; koehler et al., 2019). we investigated the effect of removal of dna complex and ...202032706389
quinoline-triazole half-sandwich iridium(iii) complexes: synthesis, antiplasmodial activity and preliminary transfer hydrogenation studies.iridium(iii) half-sandwich complexes containing 7-chloroquinoline-1,2,3-triazole hybrid ligands were synthesised and their inhibitory activities evaluated against the plasmodium falciparum malaria parasite. supporting computational analysis revealed that metal coordination to the quinoline nitrogen occurs first, forming a kinetic product that, upon heating over time, forms a more stable cyclometallated thermodynamic product. single crystal x-ray diffraction confirmed the proposed molecular struc ...202032697227
low density lipoprotein receptor variants in the beta-propeller subdomain and their functional impact.background: pathogenic variants in the low density lipoprotein receptor gene are associated with familial hypercholesterolemia. some of these variants can result in incorrect folding of the ldlr protein, which is then accumulated inside the cell and cannot fulfill its function to internalize ldl particles. we analyzed the functional impact of 10 ldlr variants localized in the beta-propeller of epidermal growth factor precursor homology domain. the experimental part of the work was complemented b ...202032695144
antibodies to the muscarinic acetylcholine receptor m3 in primary biliary cholangitis inhibit receptor function on cholangiocytes.background and aims: in primary biliary cholangitis (pbc), antibodies to a peptide of the muscarinic acetylcholine receptor 3 (machr3) have been described. since the machr3 is expressed on cholangiocytes and machr3-signaling is involved in the pathogenesis of chronic inflammatory biliary diseases, we wanted to investigate whether anti-machr3-antibodies influence the function of the receptor and the proliferative response of cholangiocytes. methods: immunoglobulins were isolated by ammonium sulfa ...202032695096
a direct rt qpcr method for quantification of retrovirus-like particles in biopharmaceutical production with cho cells.chinese hamster ovary (cho) cells are the host cell of choice for manufacturing biologic drugs, like monoclonal antibody, in the biopharmaceutical industry. retrovirus-like particles (rvlps) are made during the manufacturing process with cho cells and it is incumbent upon the manufacturer to perform risk assessment based on levels of rvlp in unprocessed bulk. quantification of rvlp using electron microscopy (em) is the standard method. however, reverse transcription based real-time pcr (rt qpcr) ...202032693202
dynamism of pi4-phosphate during interactions with human erythrocytes in entamoeba histolytica.phosphatidylinositol phosphates (pips) are involved in many cellular events as important secondary messengers. in entamoeba histolytica, a human intestinal protozoan parasite, virulence-associated mechanisms such as cell motility, vesicular traffic, trogo- and phagocytosis are regulated by pips. it has been well established that pi3p, pi4p, and pi(3,4,5)p3 play specific roles during amoebic trogo- and phagocytosis. in the present study, we demonstrated the nuclear localization of pi4p in e. hist ...202032679800
sub-microsecond electrotransfection using new modality of high frequency electroporation.micro-millisecond range electric field pulses have been used for decades to facilitate dna transfer into cells and tissues, while the growing number of clinical trials underline the strong potential of dna electroporation. in this work, we present new sub-microsecond range protocols and methodology enabling successful electrotransfection in the sub-microsecond range. to facilitate dna transfer, a 3 kv/60 a and high frequency (1 mhz) sub-microsecond range square wave generator was applied in the ...202032679337
establishment of an anti-cd20 monoclonal antibody (c20mab-60) for immunohistochemical analyses.sensitive and specific monoclonal antibodies (mabs) are needed for detecting cd20. this antigen, one of several b lymphocyte antigens, is a target for every application used in the diagnosis of b cell lymphoma. many anti-cd20 mabs have been established, although applications of these antibodies are limited. this study aims to establish sensitive and specific anti-cd20 mabs suitable for broad application, such as flow cytometry, western blotting, and immunohistochemical analyses. using the cell-b ...202032667234
metabolic engineering challenges of extending n-glycan pathways in chinese hamster ovary cells.in mammalian cells, n-glycans may include multiple n-acetyllactosamine (poly-lacnac) units that can play roles in various cellular functions and properties of therapeutic recombinant proteins. previous studies indicated that β-1,3-n-acetylglucosaminyltransferase 2 (b3gnt2) and β-1,4-galactotransferase 1 (b4galt1) are two of the primary glycosyltransferases involved in generating lacnac units. in the current study, knocking out sialyltransferase genes slightly enhanced the lacnac content (≥4 repe ...202032663509
media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation.monoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy-one that can be modified by such factors as media formulation and process conditions during production. using a design-of-experiments approach, we examined the effect of 2-f-peracetyl fucose (2fp), uridine, and g ...202032662879
random epigenetic modulation of cho cells by repeated knockdown of dna methyltransferases increases population diversity and enables sorting of cells with higher production capacities.chinese hamster ovary (cho) cells produce a large share of today's biopharmaceuticals. still, the generation of satisfactory producer cell lines is a tedious undertaking. recently, it was found that cho cells, when exposed to new environmental conditions, modify their epigenome, suggesting that cells adapt their gene expression pattern to handle new challenges. the major aim of the present study was to employ artificially induced, random changes in the dna-methylation pattern of cho cells to div ...202032662873
characterization of glutathione proteome in cho cells and its relationship with productivity and cholesterol synthesis.glutathione (gsh) plays a central role in the redox balance maintenance in mammalian cells. previous studies of industrial chinese hamster ovary cell lines have demonstrated a relationship between gsh metabolism and clone productivity. however, a thorough investigation is required to understand this relationship and potentially highlight new targets for cell engineering. in this study, we have modulated the gsh intracellular content of an industrial cell line under bioprocess conditions to furth ...202032662871
immunoglobulin fragment f(ab')2 against rbd potently neutralizes sars-cov-2 in vitro.covid-19, which is caused by the emerging human coronavirus sars-cov-2, has become a global pandemic that poses a serious threat to human health. to date, no vaccines or specific antiviral drugs have been approved for the treatment of this disease in clinic. herein, therapeutic antibodies for sars-cov-2 were obtained from hyperimmune equine plasma. first, a recombinant sars-cov-2 spike protein receptor-binding domain (rbd) was obtained in gram-level quantities through high-cell density fermentat ...202032659292
rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the cmc properties along the entire pharmaceutical process chain.the discovery of therapeutic monoclonal antibodies (mabs) primarily focuses on their biological activity favoring the selection of highly potent drug candidates. these candidates, however, may have physical or chemical attributes that lead to unfavorable chemistry, manufacturing, and control (cmc) properties, such as low product titers, conformational and colloidal instabilities, or poor solubility, which can hamper or even prevent development and manufacturing. hence, there is an urgent need to ...202032658605
recombinant epstein-barr virus glycoprotein 350 as a serological antigen.epstein-barr virus (ebv) glycoprotein 350 (gp350) is the most abundant glycoprotein expressed on the ebv envelope, the major target for neutralizing antibodies and also essential for virion attachment to b lymphocytes. several studies have addressed ebv gp350 as a vaccine candidate, but less commonly as a potential antigen for serological assays. the aim of the current study was to develop a diagnostic tool to quantify ebv gp350-specific igg in previously ebv-infected individuals. a construct en ...202032650039
in situ fucosylation of the wnt co-receptor lrp6 increases its endocytosis and reduces wnt/β-catenin signaling.wnt/β-catenin signaling regulates critical, context-dependent transcription in numerous physiological events. among the well-documented mechanisms affecting wnt/β-catenin activity, modification of n-glycans by l-fucose is the newest and the least understood. using a combination of chinese hamster ovary cell mutants with different fucosylation levels and cell-surface fucose editing (in situ fucosylation [isf]), we report that α(1-3)-fucosylation of n-acetylglucosamine (glcnac) in the galβ(1-4)-gl ...202032649905
lc-ms/ms-based quantitative proteomic and phosphoproteomic analysis of cho-k1 cells adapted to growth in glutamine-free media.this study aims to provide insights into the molecular mechanisms underlying adaptation of cho-k1 cells to growth in glutamine-free media and potentially identifying critical signalling proteins and pathways involved in this phenotype.202032648187
s-adenosylmethionine and methylthioadenosine boost cellular productivities of antibody forming chinese hamster ovary cells.the improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. in this study, s-(5'-adenosyl)- l-methionine (sam) and 5'-deoxy-5'-(methylthio)adenosine (mta) were found to stimulate cell specific ...202032644191
malignant tissues produce divergent antibody glycosylation of relevance for cancer gene therapy effectiveness.gene therapy approaches now allow for the production of therapeutic antibodies by healthy or cancerous human tissues directly in vivo, and, with an increasing number of gene delivery methods available, the cell type for expression can be chosen. yet, little is known about the biophysical changes introduced by expressing antibodies from producer cells or tissues targeted by gene therapy approaches, nor about the consequences for the type of glycosylation. the effects of different glycosylation on ...202032643525
improving the reaction mix of a pichia pastoris cell-free system using a design of experiments approach to minimise experimental effort.a renaissance in cell-free protein synthesis (cfps) is underway, enabled by the acceleration and adoption of synthetic biology methods. cfps has emerged as a powerful platform technology for synthetic gene network design, biosensing and on-demand biomanufacturing. whilst primarily of bacterial origin, cell-free extracts derived from a variety of host organisms have been explored, aiming to capitalise on cellular diversity and the advantageous properties associated with those organisms. however, ...202032637667
what cho is made of: variations in the biomass composition of chinese hamster ovary cell lines.cell line-specific, genome-scale metabolic models enable rigorous and systematic in silico investigation of cellular metabolism. such models have recently become available for chinese hamster ovary (cho) cells. however, a key ingredient, namely an experimentally validated biomass function that summarizes the cellular composition, was so far missing. here, we close this gap by providing extensive experimental data on the biomass composition of 13 parental and producer cho cell lines under various ...202032619503
improving chinese hamster ovary host cell protein elisa using ella®: an automated microfluidic platform.chinese hamster ovary (cho) cells are a mammalian cell line used in the production of therapeutic proteins. host cell proteins (hcps) are process-related impurities that are derived from the host cell expression system. during biopharmaceutical drug development, removal of hcps is required. enzyme-linked immunosorbent assay (elisa) is a common technique to quantitate hcps, but is a labor-intensive process that takes up to 7 h. ella® is an automated instrument that utilizes microfluidics and glas ...202032615786
directed evolution approach to enhance efficiency and speed of outgrowth during single cell subcloning of chinese hamster ovary cells.chinese hamster ovary (cho) cells are the working horse of the pharmaceutical industry. to obtain high producing cell clones and to satisfy regulatory requirements single cell cloning is a necessary step in cell line development. however, it is also a tedious, labor intensive and expensive process. here we show an easy way to enhance subclonability using subcloning by single cell sorting itself as the selection pressure, resulting in improved subcloning performance of three different host cell l ...202032612755
the p.p888l sap97 polymorphism increases the transient outward current (ito,f) and abbreviates the action potential duration and the qt interval.synapse-associated protein 97 (sap97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates na+ and k+ channels. here we compared the electrophysiological effects of native (wt) and p.p888l sap97, a common polymorphism. currents were recorded in cardiomyocytes from mice trans-expressing human wt or p.p888l sap97 and in chinese hamster ovary (cho)-transfected cells. the duration of the action potentials and the qt interval were significantly shorter in p.p888l-sap97 ...202032612162
functional pasta consumption in healthy volunteers modulates abcg1-mediated cholesterol efflux capacity of hdl.prevention of cardiovascular (cv) disease is considered a central issue in public health and great attention is payed to nutritional approaches, including consumption of functional foods to reduce cv risk in individuals without indications for anti-atherosclerotic drugs. cholesterol efflux capacity (cec) is an important anti-atherogenic property of hdl and a marker of cv risk. we evaluated the effect of a daily consumption of an innovative whole-wheat synbiotic pasta, compared to a control whole ...202032605885
evaluation of osteogenic/cementogenic modulating potential of pai-1 transfected media for stem cells.in vitro evaluation of the effects of plasminogen activator inhibitor-1 (pai-1) transfected-conditioned media (p-cm) on the differentiation of human periodontal ligament stem cells (hpdlscs) and human periapical follicular stem cells (hpafscs).202032603295
design, construction, and expression of recombinant human interferon beta gene in cho-s cell line using ebv-based expression system.codon optimization has been considered as a powerful strategy to increase the expression level of protein therapeutics in mammalian cells. as an empirical approach to study the effects of the codon usage and gc content on heterologous gene expression in suspension adapted chinese hamster ovary (cho-s) cells, we redesigned the recombinant human interferon beta (rhifn- β) gene based on the codon preference of the cho cell in a way to increase the gc content in the third position of each codon.202032582354
investigation into the impact of tyrosine on the product formation and quality attributes of mabs in rcho cell cultures.tyrosine (tyr) is crucial to the maintenance of the monoclonal antibody (mab) titers and quality attributes in fed-batch cultures of recombinant chinese hamster ovary (rcho) cells. however, the relation between tyrosine and these aspects is not yet fully defined. in order to further elucidate such a relation, two groups of fed-batch experiments with high tyrosine (h-t) or low tyrosine (l-t) additions producing an igg1 monoclonal antibody against cd20 were implemented to investigate the intracell ...202032577803
enabling speed to clinic for monoclonal antibody programs using a pool of clones for ind-enabling toxicity studies.the importance of speed to clinic for medicines that may address unmet medical needs puts pressure on product development timelines. historically, both toxicology and first-in-human clinical materials are generated using the same clonal-derived cells to ensure safety and minimize any development risks. however, cell line development with single cell cloning is time consuming, and aggravated by the time needed to screen for a lead clone based on cell line stability and manufacturability. in order ...202032449878
modulation of acid-sensing ion channels by hydrogen sulfide.acid-sensing ion channels (asics) have been implicated in many physiological and patho-physiological processes like synaptic plasticity, inflammation, pain perception, stroke-induced brain damage and, drug-seeking behaviour. although asics have been shown to be modulated by gasotransmitters like nitric oxide (no), their regulation by hydrogen sulfide (h2s) is not known. here, we present strong evidence that h2s potentiates asics-mediated currents. low ph-induced current in chinese hamster ovary ...202032446393
production of integrin αiibβ3 in stably transfected and clonal chinese hamster ovary cells for functional and structural studies. 202032445462
impacts on product quality attributes of monoclonal antibodies produced in cho cell bioreactor cultures during intentional mycoplasma contamination events.a mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2-µm filters used in the clarification of harvested cell culture fluid. previously, we reported a study regarding the ability of mycoplasma arginini to persist in a single-use, perfusion rocking bioreactor system containing a chinese hamster ovary (cho) dg4 ...202032436993
overexpression of the mitochondrial pyruvate carrier reduces lactate production and increases recombinant protein productivity in cho cells.chinese hamster ovary (cho) cells are characterized by a low glucose catabolic efficiency, resulting in undesirable lactate production. here, it is hypothesized that such low efficiency is determined by the transport of pyruvate into the mitochondria. the mitochondrial pyruvate carrier (mpc), responsible for introducing pyruvate into the mitochondria, is formed by two subunits, mpc1 and mpc2. stable cho cell lines, overexpressing the genes of both subunits, were constructed to facilitate the ent ...202032436990
using metabolomics to identify cell line-independent indicators of growth inhibition for chinese hamster ovary cell-based bioprocesses.chinese hamster ovary (cho) cells are widely used for the production of biopharmaceuticals. efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. in addition to ammonia and lactate, many other metabolites accumulate in cho cell cultures, although their effects remain largely unknown. elucidating these effects has the potential to further improve ...202032429145
small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in chinese hamsters with type 2 diabetes mellitus.type 2 diabetes mellitus (t2dm) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (ir), or both. chinese hamsters have potential value as non-obese animal models of spontaneous t2dm for studying the pathogenesis and molecular characteristics of diabetes. in this study, the molecular characteristics of the chinese hamster diabetes animal model were investigated through small intestine proteomics and ...202032428569
biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study.process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. this case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-l scale (process a, n = 5) to intensified processing schemes at both 1000-l (process b, n = 8) and 2000-l scales (process c, n = 3) for the production of a monoclonal antibody by a chinese hamster ovary cell line. for the upstream part of the process, we implemented an inte ...202032425110
rich production media as a platform for cho cell line development.recent cell culture media for mammalian cells can be abundantly formulated with nutrients supporting production, but such media can be limited to use in host cell culture, transfection, cell cloning, and cell growth under the low cell density conditions. in many cases, appropriate platform media are used for cell line development, and then replaced with rich media for production. in this study, we demonstrate rich chemically defined media for chinese hamster ovary (cho) cells that are suitable a ...202032415509
atypical chemokine receptor ackr2-v41a has decreased ccl2 binding, scavenging, and activation, supporting sustained inflammation and increased alzheimer's disease risk.a recent genome-wide association study (gwas) of 59 cerebrospinal fluid (csf) proteins with a connection to alzheimer's disease (ad) demonstrated an association between increased levels of chemokine ligand 2 (ccl2) with an atypical chemokine receptor chemokine-binding protein 2 variant v41a (ackr2-v41a; rs2228467). high levels of ccl2 are associated with increased risk of ad development as well as other inflammatory diseases. in this study we characterized the biological function of the ackr2-v4 ...202032415244
cellular reference materials for dna damage using electrochemical oxidation.reference materials are needed to quantify the level of dna damage in cells, to assess sources of measurement variability and to compare results from different laboratories. the comet assay (single cell gel electrophoresis) is a widely used method to determine dna damage in the form of strand breaks. here we examine the use of electrochemical oxidation to produce dna damage in cultured mammalian cells and quantify its percentage using the comet assay. chinese hamster ovary (cho) cells were grown ...202032411438
proteoglycan-dependent endo-lysosomal fusion affects intracellular survival of salmonella typhimurium in epithelial cells.proteoglycans (pgs) are glycoconjugates which are predominately expressed on cell surfaces and consist of glycosaminoglycans (gags) linked to a core protein. an initial step of gags assembly is governed by the β-d-xylosyltransferase enzymes encoded in mammals by the xylt1/xylt2 genes. pgs are essential for the interaction of a cell with other cells as well as with the extracellular matrix. a number of studies highlighted a role of pgs in bacterial adhesion, invasion, and immune response. in this ...202032411142
chromosome-scale scaffolds for the chinese hamster reference genome assembly to facilitate the study of the cho epigenome.the chinese hamster genome serves as a reference genome for the study of chinese hamster ovary (cho) cells, the preferred host system for biopharmaceutical production. recent re-sequencing of the chinese hamster genome resulted in the refseq picr meta-assembly, a set of highly accurate scaffolds that filled over 95% of the gaps in previous assembly versions. however, these scaffolds did not reach chromosome-scale due to the absence of long-range scaffolding information during the meta-assembly p ...202032410221
the relation of bleomycin delivery efficiency to microbubble sonodestruction and cavitation spectral characteristics.the concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. experiments were conducted on chinese hamster ovary cells coadministered with sonovue microbubbles. detailed analysis of the scattering and attenuation temporal functions culminated in q ...202032385397
receptor-targeted photodynamic therapy of glucagon-like peptide 1 receptor-positive lesions.treatment of hyperinsulinemic hypoglycemia is challenging. surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism is invasive and carries major risks of morbidity. medication to treat nesidioblastosis and diffuse congenital hyperinsulinism has varying efficacy and causes significant side effects. here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing β-cells by receptor-targeted photodynamic therapy (rtpdt) with exend ...202032385165
effects of gentiana delavayi flower extract on app processing in app/ps1 cho cells.gentiana delavayi franch. (gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. in this study we investigated the influence of g. delavayi flower extract on amyloid precursor protein (app) processing at molecular and cellular levels. app/ps1 chinese hamster ovary (cho) cells were treated with chloroform extract of g. delavayi flower ...202032378555
expression vector cassette engineering for recombinant therapeutic production in mammalian cell systems.human tissue plasminogen activator was the first recombinant therapy protein that successfully produced in chinese hamster ovary cells in 1986 and approved for clinical use. since then, more and more therapeutic proteins are being manufactured in mammalian cells, and the technologies for recombinant protein production in this expression system have developed rapidly, with the optimization of both upstream and downstream processes. one of the most promising strategies is expression vector cassett ...202032372203
one-step enrichment of intact glycopeptides from glycoengineered chinese hamster ovary cells.recently, the glycoproteomic analysis of intact glycopeptides has emerged as an effective approach to decipher the glycan modifications of glycoproteins at the site-specific level. a rapid method to enrich intact glycopeptides is essential for the analysis of glycoproteins, especially for biopharmaceutical proteins. in this study, we established a one-step method for the rapid capture of intact glycopeptides for analysis by mass spectrometry. compared to the conventional sequential enrichment me ...202032363175
an efficient screening system in yeast to select a hyperactive piggybac transposase for mammalian applications.as non-viral transgenic vectors, the piggybac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. however, further improvements in transpose activity are required for industrialization and clinical applications. herein, we established a one-plasmid effective screening system and a two ...202032357554
kcnq1 antibodies for immunotherapy of long qt syndrome type 2.patients with long qt syndrome (lqts) are predisposed to life-threatening arrhythmias. a delay in cardiac repolarization is characteristic of the disease. pharmacotherapy, implantable cardioverter-defibrillators, and left cardiac sympathetic denervation are part of the current treatment options, but no targeted therapy for lqts exists to date. previous studies indicate that induced autoimmunity against the voltage-gated kcnq1 k+ channels accelerates cardiac repolarization.202032354382
dynamic modeling of cho cell metabolism using the hybrid cybernetic approach with a novel elementary mode analysis strategy.chinese hamster ovary (cho) cell culture has a major importance on the production of biopharmaceuticals, including recombinant therapeutic proteins such as monoclonal antibodies (mab). mathematical modeling of biological systems can successfully assess metabolism complexity while providing logical and systematic methods for relevant genetic target and culture parameter identification toward cell growth and productivity improvements. most modeling approaches on cho cells have been performed under ...202032351947
subphysiological temperature induces pervasive alternative splicing in chinese hamster ovary cells.rna sequencing (rnaseq) has been widely used to associate alterations in chinese hamster ovary (cho) cell gene expression with bioprocess phenotypes; however, alternative messenger rna (mrna) splicing, has thus far, received little attention. in this study, we utilized rnaseq for transcriptomic analysis of a monoclonal antibody (mab) producing cho k1 cell line subjected to a temperature shift. more than 2,465 instances of differential splicing were observed 24 hr after the reduction of cell cult ...202032346860
a doubly auxotrophic cho-k1 cell line for the production of recombinant monoclonal antibodies.chinese hamster ovary (cho) cells are the most widely used mammalian hosts for recombinant protein production due to their hardiness, ease of transfection, and production of glycan structures similar to those in natural human monoclonal antibodies. to enhance the usefulness of cho-k1 cells we developed a new selection system based on double auxotrophy. we used crispr-cas9 to knockout the genes that encode the bifunctional enzymes catalyzing the last two steps in the de novo synthesis of pyrimidi ...202032346859
antimicrobial activity, toxicity and accumulated hard-tissue debris (ahtd) removal efficacy of several chelating agents.to evaluate the antimicrobial, toxicity and cleaning effectiveness of ethylenediaminetetraacetic acid (edta) and maleic acid (ma) alone and combined with cetrimide (ctr).202032344451
optimization of parameters affecting on cho cell culture producing recombinant erythropoietin.several factors may affect erythropoietin (epo) sugar structures including designing cell culture procedure, ph, concentration of additives, dissolved oxygen, and other physicochemical parameters. in this study, we investigated the influence of changes in effective parameters and compounds on the growth rate of chinese hamster ovary cell (cho) cells producing recombinant epo. cell culture was performed at different temperature, buffering conditions, and varied concentrations of additives such as ...202032336186
naturally occurring variants in the transmembrane and cytoplasmic domains of the human coxsackie- and adenovirus receptor have no impact on virus internalisation.the coxsackie- and adenovirus receptor (car) mediates homophilic cell-cell contacts and susceptibility to both human pathogenic viruses through its membrane-distal immunoglobulin domain. in the present study, we screened five missense variants of the human car gene for their influence on adenovector or coxsackievirus entry into chinese hamster ovary cells. the car variants facilitated virus internalisation to a similar extent as wild type car. this underlines car's presumed invariance and essent ...202032334832
short communication: the essential role of n-glycosylation in the transport activity of bovine peptide transporter 2.bovine peptide transporter 2 (bpept2), which mediates the absorption of di- and tripeptides in the bovine mammary gland, was predicted to contain multiple putative n-glycosylation sites of asparagine residues. n-linked glycosylation is proven to be essential for the folding, stability, localization, and substrate binding of nutrient transporters and could therefore potentially have an essential role in the function of bpept2. this study investigated the effect of mutagenesis of n-glycosylation s ...202032331895
enzyme capacity-based genome scale modelling of cho cells.chinese hamster ovary (cho) cells are most prevalently used for producing recombinant therapeutics in biomanufacturing. recently, more rational and systems approaches have been increasingly exploited to identify key metabolic bottlenecks and engineering targets for cell line engineering and process development based on the cho genome-scale metabolic model which mechanistically characterizes cell culture behaviours. however, it is still challenging to quantify plausible intracellular fluxes and d ...202032330653
biological filtering and substrate promiscuity prediction for annotating untargeted metabolomics.mass spectrometry coupled with chromatography separation techniques provides a powerful platform for untargeted metabolomics. determining the chemical identities of detected compounds however remains a major challenge. here, we present a novel computational workflow, termed extended metabolic model filtering (emmf), that aims to engineer a candidate set, a listing of putative chemical identities to be used during annotation, through an extended metabolic model (emm). an emm includes not only can ...202032326153
genotoxicity of micro- and nano-particles of kaolin in human primary dermal keratinocytes and fibroblasts.kaolin is a clay mineral with the chemical composition al2si2o5(oh)4. it is an important industrial material, and is also used as a white cosmetic pigment. we previously reported that fine particles of kaolin have genotoxic potency to chinese hamster ovary cho aa8 cells, and to the lungs of c57bl/6 j and icr mice. in the present study, we evaluated the genotoxicity of different particle sizes of kaolin using primary normal human diploid epidermal keratinocytes and primary normal human diploid de ...202032322315
dna nanovaccines prepared using lema antigen protect golden syrian hamsters against leptospira lethal infection.nanoparticles (nps) are viable candidates as carriers of exogenous materials into cells via transfection and can be used in the dna vaccination strategy against leptospirosis.202032321154
multiplex secretome engineering enhances recombinant protein production and purity.host cell proteins (hcps) are process-related impurities generated during biotherapeutic protein production. hcps can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. here, we present an effort to create a "clean" chinese hamster ovary (cho) cell by disrupting multiple genes to eliminate hcps. using a model of cho cell protein secretion, we predict that the elimination of unnecessary hcps could have a non-negligible impact on ...202032313013
a high-resolution measurement of nucleotide sugars by using ion-pair reverse chromatography and tandem columns.n-linked glycosylation is a cellular process transferring sugars from glycosyl donors to proteins or lipids. biopharmaceutical products widely produced by culturing mammalian cells such as chinese hamster ovary (cho) cells are typically glycosylated during biosynthesis. for some biologics, the n-linked glycan is a critical quality attribute of the drugs. nucleotide sugars are the glycan donors and impact the intracellular glycosylation process. in current analytical methods, robust separation of ...202032300845
development of a scale-up strategy for chinese hamster ovary cell culture processes using the kl a ratio as a direct indicator of gas stripping conditions.herein, we described a scale-up strategy focused on the dissolved carbon dioxide concentration (dco2 ) during fed-batch cultivation of chinese hamster ovary cells. a fed-batch culture process for a 2000-l scale stainless steel (ss) bioreactor was scaled-up from similarly shaped 200-l scale bioreactors based on power input per unit volume (p/v). however, during the 2000-l fed-batch culture, the dco2 was higher compared with the 200-l scale bioreactor. therefore, we developed an alternative approa ...202032298540
combining lipoic acid to methylene blue reduces the warburg effect in cho cells: from tca cycle activation to enhancing monoclonal antibody production.the warburg effect, a hallmark of cancer, has recently been identified as a metabolic limitation of chinese hamster ovary (cho) cells, the primary platform for the production of monoclonal antibodies (mab). metabolic engineering approaches, including genetic modifications and feeding strategies, have been attempted to impose the metabolic prevalence of respiration over aerobic glycolysis. their main objective lies in decreasing lactate production while improving energy efficiency. although yield ...202032298377
electroceutical silk-silver gel to eradicate bacterial infection.with more than 50% of bacteria resistant to standard antibiotics, new strategies to treat bacterial infection and colonization are needed. based on the concept of targeting the bacteria synergistically on various fronts, it is hypothesized that an electrical insult associated with antibacterial materials may be a highly effective means of killing bacteria. in this work, an injectable conductive gel based on silk fibroin (sf) and silver nanoparticles (ag-nps) is synthesized, capable of coating a ...202032293155
immunogenicity risk assessment for an engineered human cytokine analogue expressed in different cell substrates.the purpose of this article is to illustrate how performance of an immunogenicity risk assessment at the earliest stage of product development can be instructive for critical early decision-making such as choice of host system for expression of a recombinant therapeutic protein and determining the extent of analytical characterization and control of heterogeneity in co- and post-translational modifications. application of a risk-based approach for a hypothetical recombinant dna analogue of a hum ...202032291556
patches and blebs: a comparative study of the composition and biophysical properties of two plasma membrane preparations from cho cells.this study was aimed at preparing and characterizing plasma membranes (pm) from chinese hamster ovary (cho) cells. two methods of pm preparation were applied, one based on adhering cells to a poly-lysine-coated surface, followed by hypotonic lysis and removal of intracellular components, so that pm patches remain adhered to each other, and a second one consisting of bleb induction in cells, followed by separation of giant plasma membrane vesicles (gpmv). both methods gave rise to pm in sufficien ...202032290157
fam83g is a novel inducer of apoptosis.the family with sequence similarity 83 (fam83) protein family g (fam83g) possesses a predicted consensus phosphorylation motif for serine/threonine-protein kinase d1/protein kinase c mu (pkd1/pkcμ) at serine residue 356 (s356). in this study, overexpressed wild-type fam83g coimmunoprecipitated with pkd1/pkcμ in chinese hamster ovary (cho) cells inhibited heat shock protein 27 (hsp27) phosphorylation at s82 and reduced the living cell number. the expression of a fam83g phosphorylation-resistant m ...202032570757
construction of an expression vector mediated by the dual promoter for prokaryotic and mammalian cell expression system.the aim of this study was to construct an expression vector mediated by the dual promoter that can simultaneously drive the recombinant protein production in eukaryotic and prokaryotic cells. the prokaryotic t7 promoter and ribosome binding site (rbs) was cloned downstream of cmv promoter in the eukaryotic expression vector pires-neo, and t7 termination sequence was inserted upstream of neomycin phosphotransferase gene to generate the dual promoter vector. the enhanced green fluorescent protein ...202032564228
expanding the chinese hamster ovary cell long noncoding rna transcriptome using rnaseq.our ability to study chinese hamster ovary (cho) cell biology has been revolutionised over the last decade following the development of next generation sequencing technology and publication of reference dna sequences for cho cells and the chinese hamster. rna sequencing has not only enabled the association of transcript expression with bioreactor conditions and desirable bioprocess phenotypes but played a key role in the characterisation of protein coding and small noncoding rnas. the annotation ...202032558938
lycopene alleviates oxidative stress via the pi3k/akt/nrf2pathway in a cell model of alzheimer's disease.oxidative stress (os) plays an important role in neurodegenerative diseases such as alzheimer's disease (ad). lycopene is a pigment with potent antioxidant and anti-tumor effects. however, its potential role in central nervous system is not well-defined. the aim of this study was to investigate the effect of lycopene on the cell model of ad and determine its underlying mechanisms.202032551202
cytotoxicity and mutagenicity of narrowband uvb to mammalian cells.phototherapy using narrowband ultraviolet-b (nb-uvb) has been shown to be more effective than conventional broadband uvb (bb-uvb) in treating a variety of skin diseases. to assess the difference in carcinogenic potential between nb-uvb and bb-uvb, we investigated the cytotoxicity via colony formation assay, genotoxicity via sister chromatid exchange (sce) assay, mutagenicity via hypoxanthine phosphoribosyltransferase (hprt) mutation assay, as well as cyclobutane pyrimidine dimer (cpd) formation ...202032545288
applications of small molecules in modulating productivity and product quality of recombinant proteins produced using cell cultures.mammalian cell cultures have been used extensively for production of recombinant protein therapeutics such as monoclonal antibodies, fusion proteins and enzymes for decades. small molecules have been investigated as media supplements to improve process productivity and reduce cost of goods. those chemicals can lead to significant yield improvement through different mechanisms such as cell cycle modulation, cellular redox regulation, etc. in addition to productivity, small molecules have also bee ...202032540474
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