The productivity of stably transfected cell lines is of critical importance for the manufacturing of therapeutic proteins. Various methods have been successfully implemented to increase the production output of mammalian cell cultures. Increasing evidence suggests that optimization of the gene coding sequences of an expression vector can improve specific cell line yield of the recombinant protein. Here we demonstrate that gene optimization substantially enhances antibody production in Chinese hamster ovary cells. When gene optimization was applied to the heavy and light chain genes of a therapeutic antibody, we observed increased antibody production in transient transfection. Elevated heavy chain mRNA level was associated with the increase of antibody production. Further analysis suggested that the increased antibody expression is attributable to enhanced mRNA stability resulting from gene optimization. Gene optimization also led to increased antibody production in stable clones.
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http://dx.doi.org/10.1002/biot.200900192 | DOI Listing |
Bull Math Biol
January 2025
Information Technology Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland, 20899, USA.
Immune events such as infection, vaccination, and a combination of the two result in distinct time-dependent antibody responses in affected individuals. These responses and event prevalence combine non-trivially to govern antibody levels sampled from a population. Time-dependence and disease prevalence pose considerable modeling challenges that need to be addressed to provide a rigorous mathematical underpinning of the underlying biology.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Eli Lilly and Company, Indianapolis, IN, USA.
Background: Anti-amyloid-β (Aβ) immunotherapy trials have shown amyloid-related imaging abnormalities (ARIA) as the most common and serious adverse events linked to pathological changes in cerebral vasculature. Nevertheless, the mechanisms underlying how amyloid immunotherapy triggers vascular damage, increases vascular permeability, and results in microhemorrhages remains unclear. Notably, activation of perivascular macrophages and infiltration of peripheral immune cells have been implicated in regulating cerebrovascular damage.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Tel Aviv university, Tel Aviv, Israel, Israel.
Background: Amyloid filaments formation is a complex kinetic and thermodynamic process. The dependence of peptide polymerization on peptide-peptide interactions to form a β-pleated sheet fibrils and the stimulatory influence of other proteins on the reaction suggest that amyloid formation may be subject to modulation METHOD: In vitro formation of β-amyloid was induced by incubation of an aqueous solution of AβP (10 mg/ml) for 7 days at 37°C. The extent of β-amyloid formation and disaggregation were monitored using a panel of well characterized mAbs raised against soluble AβP fragments.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Institute for Memory Impairments and Neurological Disorders (MIND), Irvine, CA, USA.
Background: Late-onset Alzheimer's disease (LOAD) represents the majority of human AD cases, yet the availability of animal models that accurately reflect LOAD progression and pathology is limited. Traditional transgenic mouse models including 3xTg-AD and 5xFAD rely on supraphysiological overexpression of familial AD risk genes, failing to adequately replicate the disease progression observed in LOAD. Here, we present the first characterization of MODEL-AD1 (MAD1), a platform mouse developed by the Model Organism Development and Evaluation for Late-onset Alzheimer's Disease (MODEL-AD) Consortium.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.
Background: Lewy bodies (LBs), characterized by intraneuronal inclusions of misfolded alpha-synuclein (α-syn) protein, are the pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Because this protein is phosphorylated at serine-129 in 90% of LBs, its phosphorylation is considered a crucial pathogenic event in LB formation and disease development. Here, we present a unique brain autopsy case of a DLB patient with widespread LBs that were negative for phosphorylated-α-syn, challenging traditional diagnostic criteria.
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