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https://www.readbyqxmd.com/read/28335259/lipid-nanovectors-to-deliver-rna-oligonucleotides-in-cancer
#1
REVIEW
Virginia Campani, Giuseppina Salzano, Sara Lusa, Giuseppe De Rosa
The growing knowledge on the mechanisms of gene silencing and gene regulation by non-coding RNAs (ncRNA), mainly small interfering RNA (siRNA) and microRNA (miRNA), is providing a significant boost to the development of new therapeutic strategies for the treatment of cancer. However, the design of RNA-based therapeutics is hampered by biopharmaceutical issues, thus requiring the use of suitable delivery strategies. In this regards, lipid nanovectors have been successfully investigated to deliver RNA in different forms of cancer...
July 9, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28330101/the-aggregation-of-cytochrome-c-may-be-linked-to-its-flexibility-during-refolding
#2
James I Austerberry, Daniel J Belton
Large-scale expression of biopharmaceutical proteins in cellular hosts results in production of large insoluble mass aggregates. In order to generate functional product, these aggregates require further processing through refolding with denaturant, a process in itself that can result in aggregation. Using a model folding protein, cytochrome C, we show how an increase in final denaturant concentration decreases the propensity of the protein to aggregate during refolding. Using polarised fluorescence anisotropy, we show how reduced levels of aggregation can be achieved by increasing the period of time the protein remains flexible during refolding, mediated through dilution ratios...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28328761/drug-efficacy-monitoring-in-pharmacotherapy-of-multiple-sclerosis-with-biological-agents
#3
M Caldano, W Raoul, T Rispens, A Bertolotto
Multiple Sclerosis (MS) is a heterogeneous disease. Although several EMA approved Disease Modifying Treatments including biopharmaceuticals are available, their efficacy is limited and a certain percentage of patients are always non-responsive. Drug Efficacy Monitoring is an important tool to identify these non-responsive patients early on. Currently, Detection of Anti-Drug Antibodies and quantification of Biological Activity are used as methods of efficacy monitoring for Interferon beta (IFNβ) and Natalizumab (NAT) therapies...
March 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28328760/current-practice-for-therapeutic-drug-monitoring-of-biopharmaceuticals-in-inflammatory-bowel-disease
#4
Iris Detrez, Thomas Van Stappen, María Dolores Martín Arranz, Kostas Papamichael, Ann Gils
Since the late nineties, biopharmaceuticals targeting tumor necrosis factor α have revolutionized the treatment of moderately to severely active inflammatory bowel disease. The robust efficacy witnessed in many patients stands in stark contrast with the observation of a proportion of patients who fail to respond or who lose response over time. Therapeutic drug monitoring has been proposed as a means to understand and respond to the variability in clinical response and remission. Various treatment algorithms have been proposed, but optimal use of these measurements in daily practice awaits additional prospective validation trials...
March 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28322162/arginine-complexes-with-simvastatin-apparent-solubility-in-vitro-dissolution-and-solid-state-characterization
#5
Mmr Meor Mohd Affandi, Minaketan Tripathy, Aba Majeed
Categorized as a Biopharmaceutics Classification System (BCS) Class II drugs, statin exhibit low aqueous solubility and bioavailability thus presenting an obstacle and great challenge to formulation researchers. This paper describes a de novo approach to enhance the aqueous solubility of one of the most commonly prescribed statins i.e. simvastatin (SMV) by forming a complex (SMV-ARG) with cosolute arginine (ARG). The complex has been characterized for its apparent solubility and in vitro dissolution. The solid state characterization has been carried out using Fourier Transform Infra-Red (FTIR) Spectroscopy, Elemental Analysis, X-Ray Powder Diffraction (XRD), Differential Scanning Calorimetry (DSC) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM)...
March 20, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28320829/tissue-engineering-functional-gastrointestinal-regions-the-importance-of-stem-and-progenitor-cells
#6
Andrew Trecartin, Tracy Grikscheit
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28319811/protein-epitope-mimetic-macrocycles-as-biopharmaceuticals
#7
REVIEW
Anatol Luther, Kerstin Moehle, Eric Chevalier, Glenn Dale, Daniel Obrecht
Fully synthetic medium-sized macrocyclic peptides mimicking the key β-hairpin and α-helical protein epitopes relevant in many protein-protein interactions have emerged as a novel class of drugs with the potential to fill an important gap between small molecules and proteins. Conformationally stabilized macrocyclic scaffolds represent ideal templates for medicinal chemists to incorporate bioactive peptide and protein pharmacophores in order to generate novel drugs to treat diseases with high unmet medical need...
March 5, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28302587/transcriptomic-changes-in-cho-cells-after-adaptation-to-suspension-growth-in-protein-free-medium-analysed-by-a-species-specific-microarray
#8
Smriti Shridhar, Gerald Klanert, Norbert Auer, Inmaculada Hernandez-Lopez, Maciej M Kańduła, Matthias Hackl, Johannes Grillari, Nancy Stralis-Pavese, David P Kreil, Nicole Borth
Chinese Hamster Ovary (CHO) cells are the preferred cell line for production of biopharmaceuticals. These cells are capable to grow without serum supplementation, but drastic changes in their phenotype occur during adaptation to protein-free growth, which typically include the change to a suspension phenotype with reduced growth rate. A possible approach to understand this transformation, with the intention to counteract the reduction in growth by targeted supplementation of protein-free media, is gene expression profiling...
March 13, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28302541/trends-on-analytical-characterization-of-polysorbates-and-their-degradation-products-in-biopharmaceutical-formulations
#9
REVIEW
Ariadna Martos, Wendelin Koch, Wim Jiskoot, Klaus Wuchner, Gerhard Winter, Wolfgang Friess, Andrea Hawe
Among many other applications, polysorbates (PS) are used as the most common surfactants in biopharmaceutical products in particular to protect proteins against interfacial stress. Structural heterogeneity, presence of degradants and other impurities, and tendency for degradation are interrelated features found in commercial PS with a direct impact on their functional properties in biopharmaceutical products. These pose a challenge for the analytical characterization of PS at different stages of product development...
March 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28301581/assessing-tn5-and-sleeping-beauty-for-transpositional-transgenesis-by-cytoplasmic-injection-into-bovine-and-ovine-zygotes
#10
R J Bevacqua, R Fernandez-Martin, N G Canel, A Gibbons, D Texeira, F Lange, G Vans Landschoot, V Savy, O Briski, M I Hiriart, E Grueso, Z Ivics, O Taboga, W A Kues, S Ferraris, D F Salamone
Transgenic domestic animals represent an alternative to bioreactors for large-scale production of biopharmaceuticals and could also provide more accurate biomedical models than rodents. However, their generation remains inefficient. Recently, DNA transposons allowed improved transgenesis efficiencies in mice and pigs. In this work, Tn5 and Sleeping Beauty (SB) transposon systems were evaluated for transgenesis by simple cytoplasmic injection in livestock zygotes. In the case of Tn5, the transposome complex of transposon nucleic acid and Tn5 protein was injected...
2017: PloS One
https://www.readbyqxmd.com/read/28298216/network-reconstruction-of-the-mouse-secretory-pathway-applied-on-cho-cell-transcriptome-data
#11
Anne Mathilde Lund, Christian Schrøder Kaas, Julian Brandl, Lasse Ebdrup Pedersen, Helene Faustrup Kildegaard, Claus Kristensen, Mikael Rørdam Andersen
BACKGROUND: Protein secretion is one of the most important processes in eukaryotes. It is based on a highly complex machinery involving numerous proteins in several cellular compartments. The elucidation of the cell biology of the secretory machinery is of great importance, as it drives protein expression for biopharmaceutical industry, a 140 billion USD global market. However, the complexity of secretory process is difficult to describe using a simple reductionist approach, and therefore a promising avenue is to employ the tools of systems biology...
March 15, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28295162/evaluation-of-two-public-genome-references-for-chinese-hamster-ovary-cells-in-the-context-of-rna-seq-based-gene-expression-analysis
#12
Chun Chen, Huong Le, Chetan T Goudar
RNA-Seq is a powerful transcriptomics tool for mammalian cell culture process development. Successful RNA-Seq data analysis requires a high quality reference for read mapping and gene expression quantification. Currently, there are two public genome references for Chinese hamster ovary (CHO) cells, the predominant mammalian cell line in the biopharmaceutical industry. In this study, we compared these two references by analyzing 60 RNA-Seq samples from a variety of CHO cell culture conditions. Among the 20,891 common genes in both references, we observed that 31...
March 15, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28294302/polyclonal-and-monoclonal-igg-binding-on-protein-a-resins-evidence-of-competitive-binding-effects
#13
Justin Weinberg, Shaojie Zhang, Gillian Crews, Edward Healy, Giorgio Carta, Todd Przybycien
Protein A (ProA) chromatography is used extensively in the biopharmaceutical industry for the selective capture of both polyclonal and monoclonal antibodies (mAbs). This work provides a comparison of the adsorptive behavior of a highly heterogeneous polyclonal hIgG versus that of a mAb as well as the behavior of their mixtures on representative ProA resins. Both pH gradient elution and frontal loading experiments using human polyclonal IgG (hIgG) reveal a distribution of IgG-ProA binding strengths likely associated with multiple IgG subclasses and the heterogeneity of the variable region...
March 14, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28292680/robust-quantitation-of-basic-protein-higher-order-aggregates-using-size-exclusion-chromatography
#14
David Gervais, Andrew Downer, Darryl King, Patrick Kanda, Nicholas Foote, Stuart Smith
Detection of higher-order aggregates (HOA) using size-exclusion chromatography (SEC) was found to be variable for a basic protein, using exposed-silanol or diol-silica-based SEC columns. Preparations of the tetrameric biopharmaceutical enzyme Erwinia chrysanthemil-asparaginase (ErA), which has an isoelectric point of 8.6, were analysed using a diol-silica SEC column. Although the proportions of ErA main peak and octamer species were unaffected, HOA recovery and detection were extremely variable and had poor agreement with an orthogonal measurement technique, analytical ultracentrifugation (AUC)...
March 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28289128/characterizing-the-overall-derivatization-of-conjugated-oligomeric-proteins
#15
Michaela Wendeler, Wei Zhao, Christopher Thompson, Manuel Baca, Dhanesh Gadre, Xiangyang Wang, Harry Yang
The analysis and accurate quantitation of bioconjugations proves challenging in the case of oligomeric proteins, especially when the size of the molecule or the nature of the conjugate do not allow the analysis of the intact protein under native conditions. In this case, analytical methods are frequently applied that result in a dissociation of non-covalently linked subunits. This limits the analysis to a description of individual subunits, thereby obscuring the accurate characterization of the overall functionalization...
March 13, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28286289/mechanistic-investigation-of-the-negative-food-effect-of-modified-release-zolpidem
#16
Cord J Andreas, Xavier Pepin, Constantinos Markopoulos, Maria Vertzoni, Christos Reppas, Jennifer Dressman
AIMS: When administered orally as either an immediate or modified release dosage form, zolpidem demonstrates a negative food effect, i.e. decrease in Cmax and AUC. The aim of the study was to arrive at a better understanding of the absorption of this BCS class I compound, in vivo and to simulate the observed plasma profiles using in vitro and in silico methods. METHODS: Pharmacokinetic profiles of zolpidem are presented from a bioavailability (8mg intravenous; 10mg immediate release Stilnox®; 10mg and 12...
March 9, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28284025/editorial-thematic-issue-emerging-biopharmaceuticals-from-bioactive-peptides
#17
EDITORIAL
Dominic Agyei, Michael K Danquah, Chibuike C Udenigwe
No abstract text is available yet for this article.
2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28283956/evaluating-ultraviolet-sensitivity-of-adventitious-agents-in-biopharmaceutical-manufacturing
#18
REVIEW
Sarah M Meunier, Michael R Sasges, Marc G Aucoin
Incidents of contamination in biopharmaceutical production have highlighted the need to apply alternative or supplementary disinfection techniques. Ultraviolet (UV) irradiation is a well-established method for inactivating a broad range of microorganisms, and is therefore a good candidate as an orthogonal technique for disinfection. To apply UV as a safeguard against adventitious agents, the UV sensitivity of these target agents must be known so that the appropriate dose of UV may be applied to achieve the desired level of inactivation...
March 10, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28282262/new-insights-for-therapeutic-recombinant-human-mirnas-heterologous-production-rhodovolum-sulfidophilum-vs-escherichia-coli
#19
Patrícia Pereira, Augusto Q Pedro, João A Queiroz, Ana R Figueiras, Fani Sousa
RNA interference-based technologies have emerged as an attractive and effective therapeutic option with potential application in diverse human diseases. These tools rely on the development of efficient strategies to obtain homogeneous non-coding RNA samples with adequate integrity and purity, thus avoiding non-targeted gene-silencing and related side-effects that impair their application onto pre-clinical practice. These RNAs have been preferentially obtained by in vitro transcription using DNA templates or via chemical synthesis...
March 10, 2017: Bioengineered
https://www.readbyqxmd.com/read/28281765/reversible-macrocyclization-of-peptides-with-a-conjugate-acceptor
#20
Amber M Johnson, Eric V Anslyn
Macrocyclic peptides are an increasingly important class of biopharmaceuticals. A new method of macrocyclization is reported that involves reaction of the N-terminal amine and thiol side chain of cysteine with a Meldrum's acid derived conjugate acceptor. This reaction, which utilizes naturally occurring amino acids and requires no orthogonal protection of side chains, can also be reversed to yield the original linear peptide as desired.
March 10, 2017: Organic Letters
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