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degranulation response in cytotoxic rat lymphocytes measured with a novel cd107a antibody.measuring degranulation through cd107a expression has become an advantageous tool for testing the functional capacity of cytotoxic cells. such functional studies have been hampered in the rat by the lack of a suitable anti-rat cd107a antibody. in this study, we report a novel hybridoma generated by immunizing armenian inbred hamsters with transfected chinese hamster ovary cells expressing cd107a. the sim1 clone exhibited specific reactivity with cd107a and measured degranulation from natural kil ...201628003815
design, synthesis and biological activity of novel molecules designed to target parp and dna.in order to enhance the cytotoxic potential of poly(adp-ribose) polymerase (parp) inhibitors in brca1 or 2 deficient tumours, we designed a series of molecules containing a 1,2,3-triazene moiety tethered to a parp targeting scaffold. a cell-based selectivity assay involving a brca2-deficient chinese hamster cell line and its corresponding brca2 wild type transfectant, was used to predict the parp targeting potential of the latter agents. the results showed that adding a dna damaging function to ...201728003142
plasma membrane organization and dynamics is probe and cell line dependent.the action and interaction of membrane receptor proteins take place within the plasma membrane. the plasma membrane, however, is not a passive matrix. it rather takes an active role and regulates receptor distribution and function by its composition and the interaction of its lipid components with embedded and surrounding proteins. furthermore, it is not a homogenous fluid but contains lipid and protein domains of various sizes and characteristic lifetimes which are important in regulating recep ...201627998689
intracellular cho cell metabolite profiling reveals steady-state dependent metabolic fingerprints in perfusion culture.perfusion cell culture processes allow the steady-state culture of mammalian cells at high viable cell density, which is beneficial for overall product yields and homogeneity of product quality in the manufacturing of therapeutic proteins. in this study, the extent of metabolic steady state and the change of the metabolite profile between different steady states of an industrial chinese hamster ovary (cho) cell line producing a monoclonal antibody (mab) was investigated in stirred tank perfusion ...201627997765
preferential hydrolysis of truncated oxidized glycerophospholipids by lysosomal phospholipase a2.truncated oxidized glycerophospholipids (ox-pls) are bioactive lipids resulting from oxidative stress. the catabolic pathways for truncated ox-pls are not fully understood. lysosomal phospholipase a2 (lpla2) with phospholipase a and transacylase activities is a key enzyme in phospholipid homeostasis. the present study assessed whether lpla2 could hydrolyze truncated ox-pls. incubation of lpla2 with liposomes consisting of 1,2-o-octadecenyl-sn-glycero-3-phosphocholine (dodpc)/1,2-dioleoyl-sn-glyc ...201727993948
hiv protease inhibitors alter amyloid precursor protein processing via β-site amyloid precursor protein cleaving enzyme-1 translational up-regulation.mounting evidence implicates antiretroviral (arv) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of hiv-associated neurocognitive disorders in the post-arv era. based on their ability to induce endoplasmic reticulum (er) stress in various cell types, we hypothesized that arv-mediated er stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (app) proc ...201727993242
high-throughput lipidomic and transcriptomic analysis to compare sp2/0, cho, and hek-293 mammalian cell lines.a combined lipidomics and transcriptomics analysis was performed on mouse myeloma sp2/0, chinese hamster ovary (cho), and human embryonic kidney (hek) cells in order to compare widely used mammalian expression systems. initial thin layer chromatography (tlc) analysis indicated that phosphatidylethanolamine (pe) and phosphatidylcholine (pc) were the major lipid components in all cell lines with lower amounts of sphingomyelin (sm) in sp2/0 compared to cho and hek, which was subsequently confirmed ...201727991764
transient and stable cho expression, purification and characterization of novel hetero-dimeric bispecific igg antibodies.igg bispecific antibodies (bsabs) represent one of the preferred formats for bispecific antibody therapeutics due to their native-like igg properties and their monovalent binding to each target. most reported studies utilized transient expression in hek293 cells to produce bsabs. however, the expression of biotherapeutic molecules using stable cho cell lines is commonly used for biopharmaceutical manufacturing. unfortunately, limited information is available in the scientific literature on the e ...201627977915
bioreactor productivity and media cost comparison for different intensified cell culture processes.process intensification in biomanufacturing has attracted a great deal of interest in recent years. manufacturing platform improvements leading to higher cell density and bioreactor productivity have been pursued. here we evaluated a variety of intensified mammalian cell culture processes for producing monoclonal antibodies. cell culture operational modes including fed-batch (normal seeding density or high seeding density with n-1 perfusion), perfusion, and concentrated fed-batch (cfb) were asse ...201627977910
modeling cell survival and change in amount of dna during protracted irradiation.hyper-radiosensitivity (hrs) is a well-known bioresponse under low-dose or low-dose-rate exposures. although disorder of the dna repair function, non-targeted effects and accumulation of cells in g2 have been experimentally observed, the mechanism for inducing hrs by long-term irradiation is still unclear. on the basis of biological experiments and a theoretical study, we have shown that change in the amount of dna associated with accumulation of cells in g2 enhances radiosensitivity. to demonst ...201627974510
integrated genome and protein editing swaps α-2,6 sialylation for α-2,3 sialic acid on recombinant antibodies from cho.immunoglobin g with α-2,6 sialylation has been reported to have an impact on antibody-dependent cellular cytotoxicity and anti-inflammatory efficacy. however, production of antibodies with α-2,6 sialylation from chinese hamster ovary cells is challenging due to the inaccessibility of sialyltransferases for the heavy chain n-glycan site and the presence of exclusively α-2,3 sialyltransferases. in this study, combining mutations on the fc regions to allow sialyltransferase accessibility with overe ...201727943633
knockout of a difficult-to-remove cho host cell protein, lipoprotein lipase, for improved polysorbate stability in monoclonal antibody formulations.while the majority of host cell protein (hcp) impurities are effectively removed in typical downstream purification processes, a small population of hcps are particularly challenging. previous studies have identified hcps that are challenging for a variety of reasons. lipoprotein lipase (lpl)-a chinese hamster ovary (cho) hcp that functions to hydrolyze esters in triglycerides-was one of ten hcps identified in previous studies as being susceptible to retention in downstream processing. lpl may d ...201727943242
peroxisome biogenesis and human peroxisome-deficiency disorders.peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. to investigate peroxisome biogenesis and human peroxisome biogenesis disorders (pbds) including zellweger syndrome, more than a dozen different complementation groups of chinese hamster ovary (cho) cell mutants impaired in peroxisome biogenesis are isolated as a model experime ...201627941306
synthesis and characterization of injectable sulfonate-containing hydrogels.sulfonate-containing hydrogels are of particular interest because of their tunable mechanical and swelling properties, as well as their biological effects. polysulfonate copolymers were synthesized by reacting 2-acrylamido-2-methylpropanesulfonic acid (amps), acrylamide (am), and acrylic acid (aa). we found that the incorporation rate of sulfonate-containing monomer and the molecular weight of the copolymer were significantly enhanced by increasing the ionic strength of the solution. we introduc ...201627936721
cellular engineering for therapeutic protein production: product quality, host modification, and process improvement.recombinant proteins offer many therapeutic advantages unavailable in traditional small molecule drugs, but the need for cellular versus chemical synthesis complicates production. avenues for producing therapeutic biologics are continuously expanding, and developments in biochemistry, cell biology, and bioengineering fuel new discoveries that promise safer, more efficient, and cheaper drugs for consumers. numerous approaches to express recombinant proteins exist, but escherichia coli, saccharomy ...201727933725
improving the secretory capacity of chinese hamster ovary cells by ectopic expression of effector genes: lessons learned and future directions.chinese hamster ovary (cho) cells are the preferred cell factory for the production of therapeutic glycoproteins. although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in cho cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. to this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. however, studies on effector ge ...201727931938
novel epstein-barr virus-like particles incorporating gh/gl-ebna1 or gb-lmp2 induce high neutralizing antibody titers and ebv-specific t-cell responses in immunized mice.previous epstein-barr virus (ebv) prophylactic vaccines based on the major surface glycoprotein gp350/220 as an immunogen have failed to block viral infection in humans, suggesting a need to target other viral envelope glycoproteins. in this study, we reasoned that incorporating gh/gl or gb, critical glycoproteins for viral fusion and entry, on the surface of a virus-like particle (vlp) would be more immunogenic than gp350/220 for generating effective neutralizing antibodies to prevent viral inf ...201627926486
the homologous recombination protein rad51d protects the genome from large deletions.homologous recombination (hr) is a dna double-strand break (dsb) repair pathway that protects the genome from chromosomal instability. rad51 mediator proteins (i.e. paralogs) are critical for efficient hr in mammalian cells. however, how hr-deficient cells process dsbs is not clear. here, we utilized a loss-of-function hr-reporter substrate to simultaneously monitor hr-mediated gene conversion and non-conservative mutation events. the assay is designed around a heteroallelic duplication of the a ...201627924006
role of a tachykinin-related peptide and its receptor in modulating the olfactory sensitivity in the oriental fruit fly, bactrocera dorsalis (hendel).insect tachykinin-related peptide (trp), an ortholog of tachykinin in vertebrates, has been linked with regulation of diverse physiological processes, such as olfactory perception, locomotion, aggression, lipid metabolism and myotropic activity. in this study, we investigated the function of trp (bdtrp) and its receptor (bdtrpr) in an important agricultural pest, the oriental fruit fly bactrocera dorsalis. bdtrpr is a typical g-protein coupled-receptor (gpcr), and it could be activated by the pu ...201727923683
integrin αiibβ3-dependent erk signaling is regulated by src and rho kinases in both leu33 and pro33 polymorphic isoforms.platelet integrin αiibβ3 possesses a leu/pro polymorphism at residue 33 (leu33/hpa-1a or pro33/hpa-1b). the pro33 isoform has been suggested to exhibit prothrombotic features. αiibβ3-expressing cho (chinese hamster ovary) cells on immobilized fibrinogen show activation of the map kinase family member erk2, with an enhanced erk2 activity in pro33 cells compared to leu33 cells. in our present work, we examined how the leu/pro polymorphism modulates the erk2 activation stimulated by 2 differently t ...201727923225
generation of domain-specific monoclonal antibodies against human glutaredoxin3.human glutaredoxin3 (hglrx3), which encodes a 37.4 kda protein, possesses an n-terminal trx homology domain followed by two tandem repeats of grx domains. glrx3 is expressed in many tissues and plays important roles in iron metabolism, antioxidant effect, cell proliferation and development, regulation of immune reaction, and tumorigenesis. the mechanisms underlying the biological function of glrx3 are still not clear. to facilitate the functional research of glrx3, in this study, monoclonal anti ...201627923109
a carbon dioxide stripping model for mammalian cell culture in manufacturing scale bioreactors.control of carbon dioxide within the optimum range is important in mammalian bioprocesses at the manufacturing scale in order to ensure robust cell growth, high protein yields, and consistent quality attributes. the majority of bioprocess development work is done in laboratory bioreactors, in which carbon dioxide levels are more easily controlled. some challenges in carbon dioxide control can present themselves when cell culture processes are scaled up, because carbon dioxide accumulation is a c ...201627922179
a framework to quantify karyotype variation associated with cho cell line instability at a single-cell level.chinese hamster ovary (cho) cells, the major mammalian host cells for biomanufacturing of therapeutic proteins, have been extensively investigated to enhance productivity and product quality. however, cell line instability resulting in unexpected changes in productivity or product quality continues to be a challenge. based on previous reports about causes and characteristics of production instability, we hypothesized that chromosomal rearrangements due to genomic instability are associated with ...201727922175
genotoxicity evaluation of hwanglyeonhaedok-tang, an herbal formula.hwanglyeonhaedok-tang (huanglianjiedu-tang, orengedoku-to), a traditional herbal formula, is used for the treatment of inflammatory, gastrointestinal and cardiovascular diseases.201727916588
cell compatibility of an eposimal vector mediated by the characteristic motifs of matrix attachment regions.the characteristic sequence of β-interferon matrix attachment regions (mars) can mediate transgene expression via episomal vectors in chinese hamster ovary (cho) cells. however, the host cells were from hamster ovaries, which are not suitable target cells for gene therapy. in this study, we aimed to evaluate the suitability of 12 different human cell lines as target cells for gene therapy. we transfected the cells with episomal vectors and obtained colonies stably expressing the vector products ...201627915978
potent mutagenicity of some non-planar tri- and tetrachlorinated biphenyls in mammalian cells, human cyp2e1 being a major activating enzyme.polychlorinated biphenyls (pcbs) have been classified as human carcinogens. mutagenicity of lower chlorinated biphenyls as well as activation of transcription factors by some other congeners may contribute to the carcinogenicity of pcbs. recently, we reported that human cyp2e1 activates mono- and dichlorobiphenyls to mutagens. however, mutagenicity of other pcbs and the involvement of other cyps remained unknown. in this study, chinese hamster v79-derived cell lines genetically engineered for ex ...201627913846
flavonoids from heliotropium subulatum exudate and their evaluation for antioxidant, antineoplastic and cytotoxic activities ii.the flavonoids are the largest group of phenolic compounds isolated from a wide range of higher plants. these compounds work as antimicrobials, anti-insect agents and protect plants from other types of biotic and abiotic stresses. various researchers have suggested that flavonoids possessed antioxidant, antineoplastic and cytotoxic activities. the main objective of this study was to test dichloromethane fraction of resinous exudate of heliotropium subulatum for their antioxidant, antineoplastic ...201727905025
metachromatic leukodystrophy: biochemical characterization of two (p.307glu→lys, p.318trp→cys) arylsulfatase a mutations.metachromatic leukodystrophy (mld) is a lysosomal storage disease caused by arylsulfatase a (asa) deficiency. the hallmark of the disease is central and peripheral neurodegeneration. more than 200 mutations have been identified in arsa gene so far. some of these mutations were characterized. the aim of this study is to reinforce genotype-phenotype correlation and to understand the effect of mutations on the enzyme by biochemical characterization. two missense mutations (c.919g→a, p.307glu→lys an ...201627904824
vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures.vesivirus 2117 is an adventitious agent that, in 2009, was identified as a contaminant of chinese hamster ovary cells propagated in bioreactors at a pharmaceutical manufacturing plant belonging to genzyme. the consequent interruption in supply of fabrazyme and cerezyme (drugs used to treat fabry and gaucher diseases, respectively) caused significant economic losses. vesivirus 2117 is a member of the caliciviridae, a family of small icosahedral viruses encoding a positive-sense rna genome. we hav ...201727902397
selection of chemically defined media for cho cell fed-batch culture processes.two cho cell clones derived from the same parental cho(bc®) cell line and producing the same monoclonal antibody (bc-g, a low producing clone; bc-p, a high producing clone) were tested in four basal media in all possible combinations with three feeds (=12 conditions) in fed-batch cultures. higher amino acid feeding did not always lead to higher mab production. the two clones showed differences in cell physiology, metabolism and optimal medium-feed combinations. during the phase transitions of al ...201727900626
structural and antitrypanosomal data of different carbasones of piperitone.this article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2, 4-phenyl semicarbazone 3 and 4-phenyl thiosemicarbazone 4 prepared directly in situ from essential oil of cymbopogon schoenantus, whose gc-fid and gc-ms analysis revealed piperitone as major component (68.20%). the structures of hemi-synthesized compounds were confirmed by high throughput ir, ms, (1)h and (13)c nmr based spectrometric analysis. their antiparasitic activities were evaluated in vitro ...201627900358
design and characterization of plasmids encoding antigenic peptides of aha1 from aeromonas hydrophila as prospective fish vaccines.the current investigation aimed at designing dna vaccines against aeromonas hydrophila infections. the dna vaccine candidates were designed to express two antigenic outer membrane protein (aha1) peptides and to be delivered by a nanoparticle-based delivery system. gene sequences of conserved regions of antigenic aha1 [aha1(211-381), aha1(211-381)opt, aha1(703-999) and aha1(703-999)opt] were cloned into pvax-gfp expression vector. the selected dna vaccine candidates were purified from e. coli dh5 ...201727899335
jmv2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia.oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. the purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, jmv2894 and jmv2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. the three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in chine ...201627896546
influence of npc1 genotype on the toxicity of hydroxypropyl-β-cyclodextrin, a potentially therapeutic agent, in niemann-pick type c disease models.hydroxypropyl-β-cyclodextrin (hpbcd) is an attractive drug candidate against niemann-pick type c (npc) disease. however, the safety of hpbcd treatment for npc patients remains to be elucidated. in this study, we examined the acute toxicity of hpbcd in npc1-deficient mice. when treated with hpbcd (20,000 mg/kg, subcutaneously), over half of the wild-type (npc1(+/+)) or npc1(+/-) mice died by 72 h after the injection. in contrast, all of the npc1(-/-) mice survived. marked pathophysiological chang ...201427896072
origanum majorana essential oil lacks mutagenic activity in the salmonella/microsome and micronucleus assays.the present study aimed to investigate the in vitro mutagenic activity of origanum majorana essential oil. the most abundant compounds identified by gc-ms were γ-terpinene (25.73%), α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). mutagenicity was evaluated by the salmonella/microsome test using the preincubation procedure on ta98, ta97a, ta100, ta102, and ta1535 salmonella typhimurium strains, in the absence or in the presence of metabolic activation. cytotoxicity was detecte ...201627891531
a consensus genome-scale reconstruction of chinese hamster ovary cell metabolism.chinese hamster ovary (cho) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. to elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in cho and associated them with >1,700 genes in the cricetulus griseus genome. the genome-scale metabolic model based on this reconstruction, icho1766, and cell-line-specific models for cho-k1, cho-s, a ...201627883890
cho cells can make more protein.a new comprehensive genome-scale metabolic model of chinese hamster ovary cells identifies pathways for improving biopharmaceutical protein production.201627883886
rational design of glycoengineered interferon-β analogs with improved aggregation state: experimental validation.recombinant human interferon-β (rhifn-β) used clinically has lower efficacy than expected due to protein instabilities such as aggregation. increasing molecular stability, glycoengineering has been used to improve clinical efficacy for a number of therapeutics; however, often labor-intensive trail-and-error approaches are used to identify additional glycosylation sites. in this study two rhifn-β analogs with one additional glycosylation site, l6t and s75n, identified by a rational in silico appr ...201727881683
novel role of er stress and autophagy in microcystin-lr induced apoptosis in chinese hamster ovary cells.microcystin-lr (mc-lr) is a ubiquitous peptide that exhibits strong reproductive toxicity, although the mechanistic basis for such toxicity remains largely unknown. the present study was conducted to investigate the mechanisms underlying the adverse effects of exposure to mc-lr in chinese hamster ovary (cho) cells. the results showed that mc-lr inhibited the in vitro proliferation of cho cells significantly, with an ic50 of 10 μm. moreover, mc-lr-treated cho cells revealed strong induction of ce ...201627877136
a nucleoside anticancer drug, 1-(3-c-ethynyl-β-d-ribo-pentofuranosyl)cytosine, induces depth-dependent enhancement of tumor cell death in spread-out bragg peak (sobp) of proton beam.the effect of 1-(3-c-ethynyl-β-d-ribo-pentofuranosyl)cytosine (ecyd) on proton-induced cell death was evaluated in human lung carcinoma cell line a549 and chinese hamster fibroblast cell line v79 to enhance relative biological effectiveness (rbe) within the spread-out bragg peak (sobp) of proton beams. treatment with ecyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of sobp. the p53-binding protein 1 foci forma ...201627875573
engineering translation in mammalian cell factories to increase protein yield: the unexpected use of long non-coding sineup rnas.mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. among them, chinese hamster ovary (cho) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (mabs). to improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. this review ...201627872686
segmented linear modeling of cho fed-batch culture and its application to large scale production.we describe a systematic approach to model cho metabolism during biopharmaceutical production across a wide range of cell culture conditions. to this end, we applied the metabolic steady state concept. we analyzed and modeled the production rates of metabolites as a function of the specific growth rate. first, the total number of metabolic steady state phases and the location of the breakpoints were determined by recursive partitioning. for this, the smoothed derivative of the metabolic rates wi ...201727869296
model-based investigation of intracellular processes determining antibody fc-glycosylation under mild hypothermia.despite the positive effects of mild hypothermic conditions on monoclonal antibody (mab) productivity (qmab ) during mammalian cell culture, the impact of reduced culture temperature on mab fc-glycosylation and the mechanism behind changes in the glycan composition are not fully established. the lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimization. to address this issue, a mathematical model that quantitatively describ ...201627869292
reduced cytotoxicity in pcb-exposed chinese hamster ovary (cho) cells pretreated with vitamin e.the aim of this study was to evaluate protective effects of vitamin e (50 -150 μm) in ovary cells upon cytotoxic effects induced by two structurally distinct pcb congeners - planar "dioxin-like" pcb 77 and non-planar di-ortho-substituted pcb 153 with an emphasis on identifying differences in the mechanism of vitamin e action depending on the structure of congeners. application of three bioassays confirmed that pcbs decrease ovarian cell proliferation with slightly profound effects of pcb 77. pcb ...201727865896
establishment of monoclonal antibodies against cell surface domains of asct2/slc1a5 and their inhibition of glutamine-dependent tumor cell growth.human alanine-serine-cysteine transporter 2 (asct2; slc1a5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. in this study, we generated specific monoclonal antibodies (mabs) against asct2 by establishing an asct2-expressing chinese hamster ovary cell line that was used to immunize mice and rats. the mabs km4008, km4012, and km4018 against asct2 were isolated through a cell-based screen; these specifically bound to asct2-positive c ...201727865832
phenylpropanoids from cinnamon bark reduced β-amyloid production by the inhibition of β-secretase in chinese hamster ovarian cells stably expressing amyloid precursor protein.β-amyloid (aβ) is a substance of alzheimer disease (ad), which is generated via the amyloidogenic pathway from amyloid precursor protein (app) by β-secretase and γ-secretase. inhibition of aβ production is a potential therapeutic approach to ad. thus, we tested the hypothesis that cinnamon bark (cinnamomi cortex spissus), the dried bark of cinnamomum cassia blume (lauraceae), and its constituents are beneficial to ad. the methanol extract of cinnamon bark efficiently reduced aβ40 production in c ...201627865616
glycan region of gpi anchored-protein is required for cytocidal oligomerization of an anticancer parasporin-2, cry46aa1 protein, from bacillus thuringiensis strain a1547.parasporin-2 (ps2), alternatively named cry46aa1, an anticancer protein derived from bacillus thuringiensis strain a1547, causes specific cell damage via ps2 oligomerization in the cell membrane. although ps2 requires glycosylphosphatidylinositol (gpi)-anchored proteins for its cytocidal action, their precise role is unknown. here, we report that the glycan of gpi induces ps2 oligomerization, which causes cell death. cytotoxicity, cell-binding and oligomerization of the toxin were not observed i ...201727863961
molecular characterizations of natalisin and its roles in modulating mating in the oriental fruit fly, bactrocera dorsalis (hendel).initially, natalisin (ntl) was identified from three holometabolous insect species, drosophila melanogaster, tribolium castaneum and bombyx mori, and was documented to regulate reproductive behaviours in d. melanogaster and t. castaneum. in this study, we report the sequences of the ntl precursor and its receptor (ntlr) from an important agricultural pest, bactrocera dorsalis (hendel). ntlr is a typical g-protein coupled receptor and phylogenetic analysis showed that b. dorsalis ntlr was closely ...201727862548
differences in trpc3 and trpc6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension.canonical transient receptor potential (trpc)3 and trpc6 channels of vascular smooth muscle cells (vsmcs) mediate stretch- or agonist-induced cationic fluxes, contributing to membrane potential and vascular tone. native trpc3/c6 channels can form homo- or heterotetrameric complexes, which can hinder individual trpc channel properties. the possibility that the differences in their association pattern may change their contribution to vascular tone in hypertension is unexplored. functional characte ...201727861908
assessment of organic micropollutants occurrence in treated wastewater using heat shock protein 47 stress responses in chinese hamster ovary cells and gc/ms-based non-target screening.combining bioassays and analytical chemistry screening is a powerful approach to assess organic micropollutants which are the main contributors to toxic potential in complex mixtures of treated wastewater (tww). the aim of this study was to perform a comprehensive toxicity assessment of treated effluents using stress response bioassays and then to assess the occurrence of the organic micropollutants which were responsible for this biological response using gas chromatography coupled with a mass ...201627858797
bioisosteric ferrocenyl-containing quinolines with antiplasmodial and antitrichomonal properties.bioisosteric ferrocenyl-containing quinolines and ferrocenylamines containing organosilanes and their carbon analogues, were prepared and fully characterised. the molecular structures of two ferrocenyl-containing quinolines, determined using single-crystal x-ray diffraction, revealed that the compounds crystallise in a folded conformation. the compounds were screened for their antiplasmodial activity against the chloroquine-sensitive (nf54) and cq-resistant (dd2) strains of p. falciparum, as wel ...201627858010
improved recombinant antibody production by cho cells using a production enhancer dna element with repeated transgene integration at a predetermined chromosomal site.chinese hamster ovary (cho) cells are one of the most useful host cell lines for the production of biopharmaceutical proteins. although a series of production processes have been refined to improve protein productivity and cost performance, establishing producer cells is still time-consuming and labor-intensive. recombinase-mediated site-specific gene integration into a predetermined chromosomal locus may enable predictable protein expression, reducing the laborious process of cell screening. we ...201727856232
functional effect of the mutations similar to the cleavage during platelet activation at integrin β3 cytoplasmic tail when expressed in mouse platelets.previous studies in chinese hamster ovary cells showed that truncational mutations of β3 at sites of f754 and y759 mimicking calpain cleavage regulate integrin signaling. the roles of the sequence from f754 to c-terminus and the conservative n756ity759 motif in platelet function have yet to be elaborated. mice expressing β3 with f754 and y759 truncations, or nity deletion (β3-δtnityrgt, β3-δrgt, or β3-δnity) were established through transplanting the homozygous β3-deficient mouse bone marrow cel ...201627851790
genetic analyses of novel compound heterozygous hypodysfibrinogenemia, tsukuba i: fgg c.1129+62_65 del aata and fgg c.1299+4 del a.we found a novel hypodysfibrinogenemia designated tsukuba i caused by compound heterozygous nucleotide deletions with fgg c.1129+62_65 del aata and fgg c.1299+4 del a on different alleles. the former was deep in intron 8 of fgg (ivs-8 deletion) and the latter in exon 9 of fgg (ex-9 deletion), which is translated for the γ'-chain, but not the γa-chain. a western blot analysis of plasma fibrinogen from our patient revealed an aberrant γ-chain that migrated slightly faster than the normal bβ-chain.201627837696
biogenesis of silver nanoparticles using endophytic fungus pestalotiopsis microspora and evaluation of their antioxidant and anticancer activities.an endophytic fungal strain isolated from the leaves of gymnema sylvestre was identified as pestalotiopsis microspora vj1/vs1 based on nucleotide sequencing of internal transcribed spacer region (its 1-5.8s-its 2) of 18s rrna gene (ncbi accession number kx213894). in this study, an efficient and ecofriendly approach has been reported for the synthesis of silver nanoparticles (agnps) using aqueous culture filtrate of p. microspora. ultraviolet-visible analysis confirmed the synthesis of agnps by ...201727826190
investigation on tissue specific effects of pro-apoptotic micro rnas revealed mir-147b as a potential biomarker in ovarian cancer prognosis.the development and progression of cancer can be ascribed to imbalances in gene regulation leading to aberrant cellular behavior. the loss of micro rnas (mirnas) exhibiting tumor-suppressive function has been demonstrated to be often causative for uncontrolled cell proliferation, migration or tissue infiltration. the installation of de novo tumor suppressive function by using pro-apoptotic mirnas might be a promising therapeutic approach. in addition, there is a great demand for novel biomarkers ...201627821806
production and purification of recombinant glucocerebrosidase in transgenic rice cell suspension cultures.gaucher disease, which is caused by deficiency of glucocerebrosidase (gcd), is currently treated by enzyme replacement therapy. plant-based systems produce glycoproteins and can be combined with targeting strategies to generate proteins with terminal mannose structures for macrophage uptake. however, the gliding step for the purification is essential since the produced protein still exists inside cells. in the case of rice-amylase 1a (ramy1a) secretion signal peptide, gcd protein is secreted out ...201727817046
lysosomal alpha-mannosidase and alpha-mannosidosis.lysosomal alpha-mannosidase with acidic ph optimum is ubiquitous in human tissues where is expressed in two major forms, a and b that are the product of a single gene located on chromosome 19. mutations in the gene encoding for alpha-mannosidase cause alpha- mannosidosis, an autosomal recessive disease, resulting in the accumulation of unprocessed mannose containing oligosaccharide material. this rare disease has an estimated incidence of 1/500.0.00 live births and clinically is divided into thr ...201727814608
rapid screening by cell-based fusion assay for identifying novel antivirals of glycoprotein b-mediated herpes simplex virus type 1 infection.herpes simplex virus type 1 (hsv-1) is a causative agent for a variety of diseases. although antiherpetic drugs such as acyclovir have been developed to inhibit virus replication through interaction with dna kinases, their continuous administration leads to an increase in the frequency of drug-resistant hsv-1, which is an important clinical issue that requires urgent solution. recently, we reported that the sialylated o-linked sugar t antigen (stn) and its attached peptide region (o-glycosylated ...201627803463
identification of an igg cdr sequence contributing to co-purification of the host cell protease cathepsin d.recombinant therapeutic monoclonal antibodies (mabs) must be purified from host cell proteins (hcps), dna, and other impurities present in chinese hamster ovary (cho) cell culture media. hcps can potentially result in adverse clinical responses in patients and, in specific cases, have caused degradation of the final mab product. as reported previously, residual traces of cathepsin d caused particle formation in the final product of mab-1. the current work was focused on identification of a prima ...201727798957
regulation of human cardiac kv1.5 channels by extracellular acidification.human kv1.5 channels (hkv1.5) conduct the ultra-rapid delayed rectifier potassium current (i kur), which plays an important role in action potential repolarization of atrial myocytes. the present study was undertaken to examine the effects of acidic ph on hkv1.5 wild-type (wt) and its pore mutant channels heterologously expressed in chinese hamster ovary (cho) cells using site-directed mutagenesis combined with whole-cell patch-clamp technique. both extracellular and intracellular acidifications ...201627796577
imiglucerase in the management of gaucher disease type 1: an evidence-based review of its place in therapy.gaucher disease is the first lysosomal disease to benefit from enzyme replacement therapy, thus serving as model for numerous other lysosomal diseases. alglucerase was the first glucocerebrosidase purified from placental extracts, and this was then replaced by imiglucerase - a chinese hamster ovary cell-derived glucocerebrosidase.201627790078
osmotic effects induced by pore-forming agent nystatin: from lipid vesicles to the cell.the responses of chinese hamster ovary epithelial cells, caused by the pore-forming agent nystatin, were investigated using brightfield and fluorescence microscopy. different phenomena, i.e., the detachment of cells, the formation of blebs, the occurrence of "cell-vesicles" and cell ruptures, were observed. these phenomena were compared to those discovered in giant lipid vesicles. a theoretical model, based on the osmotic effects that occur due to the size-discriminating nystatin transmembrane p ...201627788169
flexible nanopillars to regulate cell adhesion and movement.flexible polymer nanopillar substrates were used to systematically demonstrate cell alignment and migration guided by the directional formation of focal adhesions. the polymer nanopillar substrates were constructed to various height specifications to provide an extensive variation of flexibility; a rectangular arrangement created spatial confinement between adjacent nanopillars, providing less spacing in the horizontal and vertical directions. three polymer nanopillar substrates with the diamete ...201627775920
a biotin-conjugated glutathione-responsive fret-based fluorescent probe with a ferrocenyl bodipy as the dark quencher.an efficient ferrocenyl bodipy based dark quencher has been developed and employed to construct a fret-based fluorescent probe that contains a biotin moiety as a potential directing ligand for cancer cells and a glutathione-cleavable disulfide linker connecting the quencher and a distyryl bodipy fluorophore. this molecular probe is deactivated in the native form through fret followed by intramolecular charge transfer due to the ferrocenyl unit. however, upon interaction with glutathione in phosp ...201627774548
the effect of particle size on the genotoxicity of gold nanoparticles.despite the increasing biomedical applications of gold nanoparticles (aunps), their toxicological effects need to be thoroughly understood. in the present study, the genotoxic potential of commercially available aunps with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. in the comet assay, 20 and 50 nm aunps did not induce obvious dna damage in hepg2 cells at the tested concentrations, whereas 5 nm nps induced a dose-dependent increment ...201727770565
non-proton ligand-sensing domain of acid-sensing ion channel 3 is required for itch sensation.itch, the unpleasant sensation that evokes a desire to scratch, accompanies numerous skin and nervous system disorders. however, the molecular mechanisms of itch are unclear. acid-sensing ion channel 3 (asic3) is a sensor of acidic and primary inflammatory pain. the whole-cell patch clamp technique was used to determine the effect of chloroquine (cq) on asics currents in primary sensory neurons or the chinese hamster ovary cells transfected with rat asic1a or asic3. site-directed mutagenesis of ...201627770439
akt activation by evodiae fructus extract protects ovary against 4-vinylcyclohexene diepoxide-induced ovotoxicity.evodiae fructus (ef) is the dried, unripe fruit of evodia rutaecarpa benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in korea. however, scientific evidence regarding the efficacy and action mechanism of ef is lacking.201627769945
elucidation of molecular mechanism(s) of cognition enhancing activity of bacomind(®): a standardized extract of bacopa monnieri.bacopa monnieri (l.) wettst., commonly known as brahmi, is renowned in indian traditional system for its potent memory enhancing activity, which has been validated by various scientific studies.201627761079
mtorc1 signalling and eif4e/4e-bp1 translation initiation factor stoichiometry influence recombinant protein productivity from gs-chok1 cells.many protein-based biotherapeutics are produced in cultured chinese hamster ovary (cho) cell lines. recent reports have demonstrated that translation of recombinant mrnas and global control of the translation machinery via mammalian target of rapamycin (mtor) signalling are important determinants of the amount and quality of recombinant protein such cells can produce. mtor complex 1 (mtorc1) is a master regulator of cell growth/division, ribosome biogenesis and protein synthesis, but the relatio ...201627760840
evaluating the use of a cpg free promoter for long-term recombinant protein expression stability in chinese hamster ovary cells.methylated cpg dinucleotides in promoters are associated with the loss of gene expression in recombinant chinese hamster ovary (cho) cells during large-scale commercial manufacturing. we evaluated a promoter devoid of cpg dinucleotides, cpgfree, in parallel with a similar cpg containing promoter, cpgrich, for their ability to maintain the expression of recombinant enhanced green fluorescent protein (egfp) after 8 weeks of culturing.201627756290
inhibition of the ubiquitin ligase activity improves the production of biologically active fusion protein hsa-hgf in chinese hamster ovary cells.hepatocyte growth factor (hgf) is a potent multi-functional protein that stimulates proliferation, survival, motility, scattering and differentiation during growth and development, and has been considered to be a potential therapeutic agent for the treatment of a number of intractable diseases. the aim of this study was to enhance the expression of recombinant fusion protein hsa-hgf (r494e) in cho cells by inhibiting the intracellular ubiquitin ligase activity. the high stable expression sub-clo ...201627753513
molecular and functional characterization of toll-like receptor 21 in large yellow croaker (larimichthys crocea).toll-like receptor 21 (tlr21) is a non-mammalian tlr that functions similar to mammalian tlr9 in recognizing cpg dna. in the present study, we identified a tlr21 homologue, lyctlr21, from large yellow croaker (larimichthys crocea). the complete coding sequence of lyctlr21 is 2946 nucleotides long, encoding a protein of 981 amino acids. the deduced lyctlr21 protein has typical tlr domain architecture, including a signal peptide, 13 leucine-rich repeats (lrrs) in the extracellular region, a transm ...201627751918
correlations of in vitro assays for assessing cytotoxicity and biocompatibility of contact lens multipurpose solutions.to demonstrate correlations among in vitro assays used for assessing cytotoxicity of contact lens multipurpose solution (mps) and propose the use of multiple assays as a part of preclinical evaluation for mps biocompatibility assessment.201627749498
apical membrane expression of distinct sulfated glycans represents a novel marker of cholangiolocellular carcinoma.intrahepatic cholangiocarcinoma (icc) is the second most common primary liver neoplasm, followed by hepatocellular carcinoma. icc can be further subclassified as (i) perihilar and (ii) peripheral types, the latter histologically resembling small-sized intrahepatic bile ducts, such as interlobular bile ducts, cholangioles/ductules and the canals of hering. cholangiolocellular carcinoma (cocc), now classified by the world health organization as a subtype of combined hepatocellular-cholangiocarcino ...201627748735
a nanoscale polymeric penetration enhancer based on polylysine for topical delivery of proteins and peptides.to overcome the chemical penetration enhancer-associated toxicities, without sacrificing delivery efficiency, a functional ε-polylysine (epl-g-cetyl) as polymeric permeation enhancers was synthesized by the hydrophobic modification of amino groups of ε-polylysine. the obtained epl-g-cetyl nanoparticles had about 200 nm in size with narrower distribution, high positive charge, and good stability. a high loading capacity (up to 17%) of the formulation provided a sustained and controlled release pa ...201627745885
lengthening of high-yield production levels of monoclonal antibody-producing chinese hamster ovary cells by downregulation of breast cancer 1.the establishment process of high-producing chinese hamster ovary (cho) cells for therapeutic protein production is usually laborious and time consuming because of the low probability of obtaining stable, high-producing clones over a long term. thus, development of an efficient approach is required to establish stable, high-producing cells. this study presents a novel method that can efficiently establish sustainably high-producing cell lines by acceleration of transgene amplification and suppre ...201727742176
specific immune response to phospholipase b-like 2 protein, a host cell impurity in lebrikizumab clinical material.host cell proteins are manufacturing process-related impurities that may co-purify with the product despite extensive efforts to optimize the purification process. the risks associated with these impurities can vary and may be patient and/or therapeutic dependent. therefore, it is critical to monitor and control the levels of these impurities in products and their potential impact on safety and efficacy. lebrikizumab is a humanized immunoglobulin g4 monoclonal antibody (mab) that binds specifica ...201727739010
case study on human α1-antitrypsin: recombinant protein titers obtained by commercial elisa kits are inaccurate.accurate titer determination of recombinant proteins is crucial for evaluating protein production cell lines and processes. even though enzyme-linked immunosorbent assay (elisa) is the most widely used assay for determining protein titer, little is known about the accuracy of commercially available elisa kits. we observed that estimations of recombinant human ø1-antitrypsin (rø1at) titer by coomassie-stained sds-page gels did not correspond to previously obtained titers obtained by a commerciall ...201627731958
chronic opioid treatment augments caveolin-1 scaffolding: relevance to stimulatory μ-opioid receptor adenylyl cyclase signaling.caveolin-1 is the predominant structural protein of caveolae, a subset of (lipid) membrane rafts that compartmentalize cell signaling. caveolin-1 binds most to g protein-coupled receptors and their signaling partners, thereby enhancing interactions among signaling cascade components and the relative activation of specific g protein-coupled pathways. this study reveals that chronic opioid exposure of μ-opioid receptor (mor) expressing chinese hamster ovary cells (mor-cho) and chronic in vivo morp ...201627726130
in vitro chromosomal aberrations induced by various shapes of multi-walled carbon nanotubes (mwcnts).iarc has classified one type of multi-walled carbon nanotubes (mwcnts), mwnt-7, as possibly carcinogenic to humans (group 2b); however, other types of mwcnt were categorized as not classifiable as to their carcinogenicity to humans (group 3). in vitro chromosomal aberration assays of mwnt-7 showed polyploid formation but not structural abnormalities. this study investigated the influence of the shape and size of mwcnt on in vitro induction of chromosomal aberrations.201627725379
small molecule additive enhances cell uptake of 5-aminolevulinic acid and conversion to protoporphyrin ix.administration of exogenous 5-aminolevulinic acid (5-ala) to cancerous tissue leads to intracellular production of photoactive protoporphyrin ix, a biosynthetic process that enables photodynamic therapy and fluorescence-guided surgery of cancer. cell uptake of 5-ala is limited by its polar structure and there is a need for non-toxic chemical additives that can enhance its cell permeation. two zinc-bis(dipicolylamine) (znbdpa) compounds were evaluated for their ability to promote uptake of 5-ala ...201627722428
real-time translocation and function of pkcβii isoform in response to nociceptive signaling via the trpv1 pain receptor.serine/threonine protein kinase c βii isoform (pkcβii) or the pain receptor transient receptor potential vanilloid 1 (trpv1) have been separately implicated in mediating heat hyperalgesia during inflammation or diabetic neuropathy. however, detailed information on the role of pkc βii in nociceptive signaling mediated by trpv1 is lacking. this study presents evidence for activation and translocation of the pkc βii isoform as a signaling event in nociception mediated by activation of trpv1 by caps ...201127721335
inhibition of glycosylation on a camelid antibody uniquely affects its fcγri binding activity.glycoengineering of mabs has become common practice in attempts to generate the ideal mab candidate for a wide range of therapeutic applications. the effects of these glycan modifications on the binding affinity of igg mabs for fcγriiia and their cytotoxicity are well known. however, little is understood about the effect that these modifications have on binding to the high affinity fcγri receptor. this study analyzed the effect of variable n-glycosylation on a human-llama hybrid mab (eg2-hfc, 80 ...201727721040
brodalumab for the treatment of psoriasis.psoriasis is a complex disease in which the alteration of the il-23/th17 axis appears to be crucial for its pathogenic mechanisms, and anti-il17 agents are rapidly becoming important therapeutic tools. brodalumab, a fully human chinese hamster ovary cell-derived immunoglobulin g2 (igg2) anti-il-17ra monoclonal antibody, is currently the most-developed treatment that binds to the il-17ra. the authors review and provide updates of efficacy and safety by several studies on brodalumab. areas covered ...201627718760
mitochondrial genome of cricetulus migratorius (rodentia: cricetidae): insights into the characteristics of the mitochondrial genome and the phylogenetic relationships of cricetulus species.cricetulus migratorius is widely distributed in the northwestern arid regions of china. here, the complete mitochondrial genome (mitogenome) of c. migratorius is reported, to our knowledge, for the first time. it was found to be 16,246bp in length, including 13 protein-coding genes (pcgs), 2 rrna genes, 22 trna genes, and one control region, and showed characteristics typical of the vertebrate mitogenome. comparative analyses of mitogenomes of cricetulus species showed that hamster mitogenomes h ...201627717890
renal drug transporters and their significance in drug-drug interactions.the kidney is a vital organ for the elimination of therapeutic drugs and their metabolites. renal drug transporters, which are primarily located in the renal proximal tubules, play an important role in tubular secretion and reabsorption of drug molecules in the kidney. tubular secretion is characterized by high clearance capacities, broad substrate specificities, and distinct charge selectivity for organic cations and anions. in the past two decades, substantial progress has been made in underst ...201627709005
reduction of ammonia and lactate through the coupling of glutamine synthetase selection and downregulation of lactate dehydrogenase-a in cho cells.chinese hamster ovary (cho) cell cultivation for production of therapeutic proteins is accompanied by production of metabolic wastes, mostly ammonia and lactate. to reduce ammonia production, the glutamine synthetase (gs) system was used to develop therapeutic monoclonal antibody (mab)-producing cho cells (sm-0.025). additionally, the lactate dehydrogenase-a (ldh-a) was downregulated with shrna to reduce lactate production in sm-0.025. the resulting mab-producing cell lines (#2, #46, and #52) pr ...201727704181
clinical applications of gonadotropins in the male.the pituitary gonadotropins, luteinizing hormone (lh), and follicle-stimulating hormone (fsh) play a pivotal role in reproduction. the synthesis and secretion of gonadotropins are regulated by complex interactions among several endocrine, paracrine, and autocrine factors of diverse chemical structure. in men, lh regulates the synthesis of androgens by the leydig cells, whereas fsh promotes sertoli cell function and thereby influences spermatogenesis. gonadotropins are complex molecules composed ...201627697201
general and genetic toxicology of enzyme-treated ginseng extract: toxicology of ginseng rh2.ginseng rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, rh2, rg3, which have potent anticancer activity. we conducted general and genetic toxicity tests to evaluate the safety of ginseng rh2+.201627695630
the utility of the in vitro micronucleus test for evaluating the genotoxicity of natural and manmade nano-scale fibres.a range of fibrous materials, including several types of asbestos and carbon fibres with nano scale diameters that had reported positive genotoxicity data (predominantly clastogenicity), were tested in the in vitro micronucleus test (oecd 487) in glp-compliant studies in chinese hamster ovary cells. out of eight materials tested, only one (crocidolite, an asbestos fibre) gave a positive response either in the presence or absence of metabolic activation (s9) and at short (3h) or extended (24h) ex ...201627692297
macrophage effector responses of horses are influenced by expression of cd154.reactive intermediates contribute to innate immunity by providing phagocytes with a mechanism of defense against bacteria, viruses and parasites. to better characterize the role of cd154 in the production of reactive intermediates, we cloned and expressed recombinant equine cd154 (reqcd154) in chinese hamster ovary (cho). in co-culture experiments, cho cells ectopically expressing reqcd154 elicited superoxide production in monocyte-derived macrophages (mdm). collectively, our results indicate th ...201627692094
functional complementation studies with x-ray-sensitive mutants of chinese hamster cells closely resembling ataxia-telangiectasia cells.in order to isolate a human gene complementing the defect in a-t-like hamster cell mutants, the mutants were used as recipients for genomic dna transfection, using either hela chromosomal dna or dna from a human cosmid library. three primary transformants with an intermediate x-ray sensitivity and almost normal sensitivity to mms, but retaining radioresistant dna synthesis (rds), were obtained. to identify the human chromosome that complements the defect in the a-t-like mutants, and to assess th ...199427687099
enhanced chromosomal response of ataxia-telangiectasia cells to specific types of dna double-strand breaks.the chromosomal response of two ataxiatelangiectasia (a-t) lymphoblastoid cell lines (a-t-pa and a-t-km) to restriction endonucleases (re) is compared with that of a normal (n-sw) lymphoblastoid cell line. the re used were pvuii (generating dna double-strand breaks with blunt termini), bamhi (cohesive termini with 4 base, 5' overhangs) and psti (cohesive termini with 4 base 3' overhangs). chromatid aberrations were analysed in cells 5 h after treatment. cells were porated using streptolysin o to ...199427687089
fish-based analysis of clonally derived cho cell populations reveals high probability for transgene integration in a terminal region of chromosome 1 (1q13).a basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. here, we constructed engineered chinese hamster ovary cell lines (cho-s) with a pcho-hvr1 vector that carried an extracellular domain of a vegf receptor (vr) fusion gene. forty-five clones with high hvr1 expression were selected for karyotype analysis. using fluorescence in situ hybridization (fish) and g-banding, we found that pcho-hvr1 was integ ...201727684722
cell-free systems based on cho cell lysates: optimization strategies, synthesis of "difficult-to-express" proteins and future perspectives.nowadays, biotechnological processes play a pivotal role in target protein production. in this context, chinese hamster ovary (cho) cells are one of the most prominent cell lines for the expression of recombinant proteins and revealed as a safe host for nearly 40 years. nevertheless, the major bottleneck of common in vivo protein expression platforms becomes obvious when looking at the production of so called "difficult-to-express" proteins. this class of proteins comprises in particular several ...201727684475
a novel fusion protein, achr-fc, ameliorates myasthenia gravis by neutralizing antiacetylcholine receptor antibodies and suppressing acetylcholine receptor-reactive b cells.most patients with myasthenia gravis (mg) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (achr) at the neuromuscular junction, which leads to muscle weakness. we developed a fusion protein, achr-fc, as a novel therapeutic biomolecule for patients with mg and examined its efficacy. achr-fc was expressed by chinese hamster ovary cells and purified. we examined the neutralizing activity and cellular cytotoxicity of achr-fc using anti-achr antibody-producing hybr ...201727677608
pharmacokinetic drug evaluation of albutrepenonacog alfa (csl654) for the treatment of hemophilia.replacement therapy for fviii/ix in hemophilia a/b is more than 50 years old following the discovery of cryoprecipitate by judith pool in 1964. on-demand therapy and prophylaxis to treat or prevent bleedings is very demanding owing to the short half-life (hl) of factor concentrates (no more than 12-14 h for fviii or 16-18 h for fix). patients are very eager to prolong the intervals between bolus. the enhanced hl of long-acting recombinant fix (rfix) concentrates seems to fulfill this expectance. ...201627677190
fx knockout cho hosts can express desired ratios of fucosylated or afucosylated antibodies with high titers and comparable product quality.during antibody dependent cell cytotoxicity (adcc) the target cells are killed by monocytes and natural killer cells. adcc is enhanced when the antibody heavy chain's core n-linked glycan lacks the fucose molecule(s). several strategies have been utilized to generate fully afucosylated antibodies. a commonly used and efficient approach has been knocking out the fut8 gene of the chinese hamster ovary (cho) host cells, which results in expression of antibody molecules with fully afucosylated glyca ...201727666939
cationic lipids bearing succinic-based, acyclic and macrocyclic hydrophobic domains: synthetic studies and in vitro gene transfer.in this communication we describe the construction of four succinic-based cationic lipids, their formulation with plasmid dna (pdna), and an evaluation of their in vitro gene delivery into chinese hamster ovarian (cho-k1) cells. the cationic lipids employed in this work possess either a dimethylamine or trimethylamine headgroup, and a macrocyclic or an acyclic hydrophobic domain composed of, or derived from two 16-atom, succinic-based acyl chains. the synthesized lipids and a co-lipid of neutral ...201727662033
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