Pharmaceutical proteins at the interfaces and the role of albumin
AbstractA critical measure of the quality of pharmaceutical proteins is the preservation of native conformations of the active pharmaceutical ingredients. Denaturation of the active proteins in any step before administration into patients could lead to loss of potency and/or aggregation, which is associated with an increased risk of immunogenicity of the products. Interfacial stress enhances protein instability as their adsorption to the air-liquid and liquid –solid interfaces are implicated in the formation of denatured proteins and aggregates. While excipients in protein formulations have been employed to reduce the ri...
Source: Biotechnology Progress - April 23, 2024 Category: Biotechnology Authors: Ketki Y. Velankar, Ellen S. Gawalt, Yi Wen, Wilson S. Meng Tags: REVIEW Source Type: research

Effects of green light supplementation with red and blue combinations of LED light spectrums on the growth and transcriptional response of Haematococcus pluvialis
In this study, the effects of green light supplementation, in the combination with red and blue light were investigated inHaematococcus pluvialis. 10% and 20% of green light supplementations were applied in 3:2 ratios of red and blue LED light combinations as an expense of red-light. Growth rates, chlorophyll concentration, and dry weight were measured to assess the growth kinetics ofH. pluvialis along with the relative transcript accumulations of four mRNAs: Rubisco, PTOX2, PsaB, and PsbS. Growth rates, chlorophyll concentrations and dry weight were found significantly higher in presence of 10% green light supplementation...
Source: Biotechnology Progress - April 21, 2024 Category: Biotechnology Authors: G. Karag ülle, M. Telli Tags: RESEARCH ARTICLE Source Type: research

Issue Information
(Source: Biotechnology Progress)
Source: Biotechnology Progress - April 18, 2024 Category: Biotechnology Tags: ISSUE INFORMATION Source Type: research

Strategies to improve CHO cell culture performance: Targeted deletion of amino acid catabolism and apoptosis genes paired with growth inhibitor supplementation
AbstractChinese hamster ovary (CHO) cells are the predominant host of choice for recombinant monoclonal antibody (mAb) expression. Recent advancements in gene editing technology have enabled engineering new CHO hosts with higher growth, viability, or productivity. One approach involved knock out (KO) of BCAT1 gene, which codes for the first enzyme in the branched chain amino acid (BCAA) catabolism pathway; BCAT1 KO reduced accumulation of growth inhibitory short chain fatty acid (SCFA) byproducts and improved culture growth and titer when used in conjunction with high-end pH-controlled delivery of glucose (HiPDOG) technolo...
Source: Biotechnology Progress - April 18, 2024 Category: Biotechnology Authors: Cynthia Lam, Alyssa Sargon, Camil Diaz, Zijuan Lai, Dewakar Sangaraju, Inn Yuk, Gavin Barnard, Shahram Misaghi Tags: RESEARCH ARTICLE Source Type: research

Single cell analysis of Chinese hamster ovary cells during a bioprocess using a novel dynamic imaging system
This article assesses a novel dynamic imaging system for single cell analysis. This data shows that comparable total cell density, viable cell density and percentage viability data shown here, generated by the imaging system, aligned well with conventional trypan blue counting methods for an industrially relevant Chinese Hamster Ovary (CHO) cell line. Furthermore, detailed statistical analysis shows that the classification system used by the PharmaFlow system can reveal trends of interest in monitoring the health of mammalian cells over a 6-day bioreactor culture. The system is also capable of sampling at-line, removing th...
Source: Biotechnology Progress - April 14, 2024 Category: Biotechnology Authors: Laura Breen, James Flynn, Adam Bergin, Evangelia Flampouri, Michael Butler Tags: RESEARCH ARTICLE Source Type: research

Monte Carlo simulation ‐guided design for size‐tuned tumor spheroid formation in 3D printed microwells
This study showed prominent steps in investigating spheroid formation, thereby leveraging the current know-how on the mechanism of tumor growth. (Source: Biotechnology Progress)
Source: Biotechnology Progress - April 13, 2024 Category: Biotechnology Authors: Ismail E ş, Ana‐Maria Theodora Ionescu, Burak M. Görmüş, Fatih Inci, Marco P. C. Marques, Nicolas Szita, Lucimara Gaziola de la Torre Tags: RESEARCH ARTICLE Source Type: research

A systemic approach to identifying sequence frameworks that decrease mAb production in a transient Chinese hamster ovary cell expression system
AbstractMonoclonal antibodies (mAbs) are often engineered at the sequence level for improved clinical performance yet are rarely evaluated prior to candidate selection for their “developability” characteristics, namely expression, which can necessitate additional resource investments to improve the manufacturing processes for problematic mAbs. A strong relationship between primary sequence and expression has emerged, with slight differences in amino acid sequence result ing in titers differing by up to an order of magnitude. Previous work on these “difficult-to-express” (DTE) mAbs has shown that these phenotypes ar...
Source: Biotechnology Progress - April 13, 2024 Category: Biotechnology Authors: Alana C. Szkodny, Kelvin H. Lee Tags: RESEARCH ARTICLE Source Type: research

Online monitoring of the respiration activity in 96 ‐deep‐well microtiter plate Chinese hamster ovary cultures streamlines kill curve experiments
In conclusion, the broad application of OTR online monitoring for CHO cell cultures in 96-deep-well plates is highlighted. The μTOM device proves as a valuable tool for high-throughput experiments, paving the way fo r diverse applications, such as media and clone screening, cytotoxicity tests, and scale-up experiments. (Source: Biotechnology Progress)
Source: Biotechnology Progress - April 12, 2024 Category: Biotechnology Authors: Anne Neuss, Nele von Vegesack, Raoul Liepelt, Jochen B üchs, Jørgen Barsett Magnus Tags: RESEARCH ARTICLE Source Type: research

Mesenchymal stem cells derived ‐exosomes enhanced amniotic membrane extract promotes corneal keratocyte proliferation
In this study, we evaluated the effects of both AME and WJ-MSC-Exos, individually and together, on the proliferation of corneal keratocytes as well as their ability to promote in vitro cell migration, wound healing, and their impact on cellular morphology. Our findings indicated that the presence of both exosomes (3  × 105 Exo/mL) and AME (50 μg/mL) synergistically enhance the proliferation of corneal keratocytes. Combined use of these solutions (3 × 105 Exo/mL + 50 μg/mL) increased cell proliferation compared to only 50 μg/mL AME treatment on day 3 (****p <  0.0001). This mixture treatmen...
Source: Biotechnology Progress - April 11, 2024 Category: Biotechnology Authors: Fatma Zehra Erkoc ‐Biradli, Berkay Erenay, Alp Ozgun, Hayriye Öztatlı, Ferda Işık, Utku Ateş, Rıfat Rasier, Bora Garipcan Tags: RESEARCH ARTICLE Source Type: research

Development of a pan ‐tau multivalent nanobody that binds tau aggregation motifs and recognizes pathological tau aggregates
AbstractAlzheimer's disease and other tauopathies are characterized by the misfolding and aggregation of the tau protein into oligomeric and fibrillar structures. Antibodies against tau play an increasingly important role in studying these neurodegenerative diseases and the generation of tools to diagnose and treat them. The development of antibodies that recognize tau protein aggregates, however, is hindered by complex immunization and antibody selection strategies and limitations to antigen presentation. Here, we have taken a facile approach to identify single-domain antibodies, or nanobodies, that bind to many forms of ...
Source: Biotechnology Progress - April 4, 2024 Category: Biotechnology Authors: Nikki McArthur, Bokyung Kang, Felix G. Rivera Moctezuma, Akber T. Shaikh, Kathryn Loeffler, Nemil N. Bhatt, Madison Kidd, Jennifer M. Zupancic, Alec A. Desai, Naima Djeddar, Anton Bryksin, Peter M. Tessier, Rakez Kayed, Levi B. Wood, Ravi S. Tags: RESEARCH ARTICLE Source Type: research

CD133 ligand ‐enhanced etoposide‐liposome complex for targeted killing of lung cancer cells
In this study, we combined nanotechnology and biotechnology to develop a CD133 ligand-modified etoposide-liposome complex (Lipo@ETP-CD133) for targeted therapy of lung cancer. The CD133 ligand targeted lung cancer stem cells, causing the composite material to aggregate at the tumor site, where high levels of ETP liposomes could exert a strong tumor-killing effect. Our research results demonstrated that this nano-drug had efficient targeting and tumor-killing effects, indicating its potential for clinical application. (Source: Biotechnology Progress)
Source: Biotechnology Progress - April 2, 2024 Category: Biotechnology Authors: Shiwei Nie, Junzheng Zhou, Xiaodong Zheng, Xudong Wei, Jinrui Zhang, Xiaojuan Shen, Weimin Zhang Tags: RESEARCH ARTICLE Source Type: research

Optimizing glutamine concentration enhances ex vivo expansion of natural killer cells through improved redox status
This study aimed to clarify the relationship between amino acid metabolism and expansion and cytotoxicity of NK cells. Based on analyzing the mino acid metabolism of NK-92 cells and Design of Experiments (DOE), we optimized the combinations and concentrations of amino acids in NK-92 cells culture medium. The results demonstrated that NK-92 cells showed a pronounced demand for glutamine, serine, leucine, and arginine, in which glutamine played a central role. Significantly, at a glutamine concentration of 13  mM, NK-92 cells expansion reached 161.9 folds, which was significantly higher than 55.5 folds at 2.5 mM. Additio...
Source: Biotechnology Progress - April 1, 2024 Category: Biotechnology Authors: Danni Ying, Guofeng Zhang, Huimin Huang, Wen ‐song Tan, Haibo Cai Tags: RESEARCH ARTICLE Source Type: research

Digital application for drug product potency target evaluation in biopharmaceutical manufacturing
AbstractBiopharmaceutical manufacturing entails a series of highly regulated steps. The manufacturing of safe and efficacious drug product (DP) requires testing of critical quality attributes (CQAs) against specification limits. DP potency concentration, which measures the dosage strength of a particular DP, is a CQA of great interest. In order to minimize the DP potency out-of-specification (OOS) risk, sterile fill finish (SFF) process adjustments may be needed. Varying the potency targets can be one such process adjustment. To facilitate such evaluation, data acquisition and statistical calculations are required. Regular...
Source: Biotechnology Progress - April 1, 2024 Category: Biotechnology Authors: Darrick Shen, Shyam Panjwani, Konstantinos Spetsieris Tags: RESEARCH ARTICLE Source Type: research

GMP implementation of a hybrid continuous manufacturing process for a recombinant non ‐mAb protein—A case study
AbstractAdvances in manufacturing technology coupled with the increased potency of new biotherapeutic modalities have created an external environment where continuous manufacturing (CM) can address a growing need. Amgen has successfully implemented a hybrid CM process for a commercial lifecycle program. In this process, the bioreactor, harvest, capture column, and viral inactivation/depth filtration unit operations were integrated together in an automated, continuous module, while the remaining downstream unit operations took place in stand-alone batch mode. CM operations are particularly suited for so-called “high mix, ...
Source: Biotechnology Progress - March 30, 2024 Category: Biotechnology Authors: Venkatesh Natarajan, Neil Soice, Johanna Mullen, David Bull Tags: RESEARCH ARTICLE Source Type: research

Modeling scalability of impurity precipitation in downstream biomanufacturing
The objective of this work is to compare isoelectric impurity precipitation behavior for a monoclonal antibody product across scales, from benchtop to pilot manufacturing. Scaling parameters such as agitation and vessel geometry were investigated, with the precipitate amount and particle size distribution (PSD) characterized via turbidity and flow imaging microscopy. Qualitative analysis of the data shows that maintaining a consistent energy dissipation rate (EDR) could be used for approximate scaling of vessel geometry and agitator speeds in the absence of more detailed simulation. For a more rigorous approach, however, a...
Source: Biotechnology Progress - March 28, 2024 Category: Biotechnology Authors: Jing Guo, Steven J. Traylor, Mohamed Agoub, Weixin Jin, Helen Hua, R. Bertrum Diemer, Xuankuo Xu, Sanchayita Ghose, Zheng Jian Li, Abraham M. Lenhoff Tags: RESEARCH ARTICLE Source Type: research