Review
Biotechnology & Applied Microbiology
Weifeng Li, Zhenlin Fan, Yan Lin, Tian-Yun Wang
Summary: This review highlights the importance of serum-free medium (SFM) in the production of recombinant therapeutic proteins (RTPs) using Chinese hamster ovary (CHO) cells, with nearly 70% of RTPs currently produced in this manner. It discusses the history, key components, preparation, and experimental design of SFM, as well as the potential benefits of small molecule compound additives in improving RTP yield and quality. Lastly, it explores the future prospects of using SFM with CHO cells for RTP production.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Thu M. Cao, Dayue Chen, Gavin C. Barnard, Amy Shen
Summary: This study explores the potential of using CHO cells for rAAV production and identifies cap protein expression as a limiting factor. By increasing cap protein expression, rAAV titers in CHO cells were comparable to those in HEK-derived rAAV, providing a foundation for potential rAAV production in CHO cells.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Review
Biotechnology & Applied Microbiology
Jun-He Zhang, Lin-Lin Shan, Fan Liang, Chen-Yang Du, Jing-Jing Li
Summary: Recombinant antibodies are a rapidly developing class of therapeutic agents, but high-level expression and production of these antibodies remain a major challenge. This review provides a comprehensive overview of various strategies for optimizing gene sequences, expression vectors, host cell lines, and glycosylation modifications to improve the efficiency and quality of recombinant antibody production.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Kirstin Meiners, Prisca Hamm, Marcus Gutmann, Jan Niedens, Agnieszka Nowak-Krol, Salvador Pane, Tessa Luehmann
Summary: The study developed three polyethylene glycol (PEG)ylated tPA bioconjugates based on the recombinant human tPA drug Alteplase using site-specific conjugation strategies. These bioconjugates showed improved proteolytic activity, slower inhibition kinetics by PAI-1, and increased hydrodynamic size.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Maja Papez, Victor Jimenez Lancho, Peter Eisenhut, Krishna Motheramgari, Nicole Borth
Summary: This study investigates the stress response of mammalian cells during recombinant protein production and identifies the genetic factors involved. By simulating nutrient stress, the cells induce the ISR signaling pathway to cope with amino acid limitation, leading to inhibition of lipid synthesis and the mTOR pathway. The study also demonstrates the effectiveness of SLAM-seq in detecting short-lived transcription factors and suggests its potential use in dynamic transcriptome profiling in CHO cells.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Kexue Liang, Hongzhen Luo, Qi Li
Summary: In this study, the effects of different perfusion culture strategies on process stability, product titer, and product quality were investigated. Continuous perfusion was found to be more effective in maintaining high levels of cell density, product titer, and quality compared to intermittent perfusion culture. Furthermore, the study optimized the perfusion culture conditions by adjusting perfusion rates and culture temperature. The optimized strategy resulted in significantly higher product titer and maintained excellent product quality.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemical Research Methods
Feiyang Zheng, Yoshinori Kawabe, Mai Murakami, Mamika Takahashi, Kyoka Nishihata, Souichiro Yoshida, Akira Ito, Masamichi Kamihira
Summary: The study developed a retrotransposon-based vector system that achieved integration of multiple transgenes into host genome and successfully introduced scFv-Fc into Chinese hamster ovary cells. Separately expressing ORF1 and ORF2 of LINE-1 efficiently regulated retrotransposition and improved specific scFv-Fc productivity.
BIOTECHNOLOGY JOURNAL
(2021)
Review
Biotechnology & Applied Microbiology
Tingting Xu, Jihong Zhang, Tianyun Wang, Xiaoyin Wang
Summary: This review focuses on the aggregation of recombinant therapeutic antibodies (RTAs), discussing factors causing aggregation during RTA production and strategies for overcoming RTA aggregation.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Raffaele Altamura, Jiten Doshi, Yaakov Benenson
Summary: Cell line development is crucial in biopharmaceutical manufacturing, but current protocols rely on random transgene integration. A novel strategy has been proposed to reduce screening effort, improve stability, and predict product titers through engineered multi-copy gene constructs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Hyeonjin Cha, Ju-Hyun Park
Summary: The addition of 30Kc19 alpha protein was found to enhance the production of EPO in CHO cell culture, with potential advantages in downstream purification process. 30Kc19 alpha could be mass-produced as a recombinant protein and delivered intracellularly to improve EPO production through metabolic pathways. The results suggest that 30Kc19 alpha has promising potential for manufacturing biopharmaceutical proteins.
APPLIED SCIENCES-BASEL
(2021)
Review
Biotechnology & Applied Microbiology
Laura Bryan, Martin Clynes, Paula Meleady
Summary: CHO cells are commonly used host cell lines for producing human therapeutic proteins. Research has focused on improving growth, titre, and productivity of CHO cells to reduce production costs. Recent interest in CHO cell engineering has led to studies on post-translational modifications affecting protein functionality.
BIOTECHNOLOGY ADVANCES
(2021)
Article
Biotechnology & Applied Microbiology
Mutsumi Takagi, Shoichi Jimbo, Tsuyoshi Oda, Yuta Goto, Masashi Fujiwara
Summary: The medium cost for continuous serum-free suspension culture of CHO cells may be decreased by the repeated collection and addition of PF containing exosomes and growth factor proteins.
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
(2021)
Article
Biochemical Research Methods
Aleksandra Stec, Monika Targonska, Edyta Karkosinska, Monika Slowik, Agata Ploska, Leszek Kalinowski, Bartosz Wielgomas, Krzysztof Waleron, Jacek Jasiecki, Szymon Dziomba
Summary: The overproduction of proteins in Chinese hamster ovary (CHO) cells can induce the secretion of extracellular vesicles (EVs), potentially leading to the packaging of overexpressed proteins into exosomes. These findings are crucial for the manufacturing of therapeutic drugs in CHO expression systems, as there is a risk of product loss during downstream processing of culture medium and the use of exosomes as nanocarriers for therapeutic proteins.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Klaus Leitner, Krishna Motheramgari, Nicole Borth, Nicolas Marx
Summary: In this study, a fast and robust nanopore Cas9-targeted sequencing (nCats) pipeline was developed to simultaneously obtain information on integration sites, the composition of the integrated sequence, and its DNA methylation status in CHO cells from the same sequencing run. The data generated by nCats provides sensitive, detailed, and correct information on transgene integration sites and expression vector structure, which can only be partially obtained by traditional Targeted Locus Amplification-seq data. Moreover, nCats allows for the analysis of DNA methylation status from the same raw data without prior DNA amplification.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Yukako Senga, Motomichi Doi, Masayoshi Onitsuka, Shinya Honda
Summary: This study establishes an approach to detect intracellular aggregates using a fluorescent-labeled artificial protein, AF.2A1, and finds that the relative amount of intracellular aggregates is correlated with the type of additives used during cell culture. Additionally, there is a moderate correlation between the relative amount of intracellular aggregates and that of extracellular aggregates, suggesting the secretion of intracellular aggregates.
CELL CHEMICAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Sara Restrepo-Pineda, Nuria Sanchez-Puig, Nestor O. Perez, Enrique Garcia-Hernandez, Norma A. Valdez-Cruz, Mauricio A. Trujillo-Roldan
Summary: This study aimed to evaluate the effect of different pre-induction temperatures on the growth of E. coli and the structure of IBs. The results showed that E. coli cultures growing at 34 degrees Celsius had a higher specific growth rate and significantly higher levels of recombinant protein in the IBs, with lower amyloid-like structure content.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Saumel Perez-Rodriguez, Greta Reynoso-Cereceda, Norma A. Valdez-Cruz, Mauricio A. Trujillo-Roldan
Summary: This study examined the impact of operational parameters on CHO cell growth and specific productivity, showing that lower values of oxygen transfer and shear stress can enhance cell concentration. Changes in glucose metabolism were also found in the higher producer cell line.
BIOPROCESS AND BIOSYSTEMS ENGINEERING
(2022)
Article
Engineering, Chemical
David Posadas-Navarro, Carlos Palacios, Abel Blancas-Cabrera, Mauricio A. Trujillo-Roldan, Martin Salinas-Vazquez, Gabriel Ascanio
Summary: The hydrodynamics of a stirred tank equipped with multiple hybrid impellers were experimentally characterized, and the results showed that the hybrid impellers provided a uniform flow distribution throughout the tank at moderate strain rates, making them an attractive alternative for fermentation processes with shear-sensitive cultures and viscous liquids.
CHEMICAL ENGINEERING & TECHNOLOGY
(2022)
Article
Plant Sciences
Alberto Campos-Lopez, Jaime A. Uribe-Lopez, Verna Cazares-Ordonez, Roberto Garibay-Orijel, Norma A. Valdez-Cruz, Mauricio A. Trujillo-Roldan
Summary: In asymbiotic or monoxenic conditions, a specific combination of flavanols and strigolactones can mimic root signaling and stimulate the growth and development of arbuscular mycorrhizal fungi.
Article
Chemistry, Applied
J. D. Lopez-Taborda, A. Vargas-Zapata, J. F. Ramirez-Vargas, N. A. Valdez-Cruz, M. A. Trujillo-Roldan, F. Orozco-Sanchez
Summary: This study developed an alternative control system for dissolved oxygen tension (DOT) in stirred tank bioreactors (STB) and evaluated its performance in terms of control error and energy dissipation rates. The results showed that the developed system effectively controlled DOT with reduced energy dissipation rate and control error.
REVISTA MEXICANA DE INGENIERIA QUIMICA
(2022)
Article
Biotechnology & Applied Microbiology
Leobardo Serrano-Carreon, Sergio Aranda-Ocampo, Karina A. Balderas-Ruiz, Antonio M. Juarez, Edibel Leyva, Mauricio A. Trujillo-Roldan, Norma A. Valdez-Cruz, Enrique Galindo
Summary: The study tested the impact of mid-tech greenhouses using biocontrol and biofertilization on tomato production, and found that this technology can significantly increase profits in middle-income countries like Mexico.
ELECTRONIC JOURNAL OF BIOTECHNOLOGY
(2022)
Article
Virology
Selene Zarate, Blanca Taboada, Mauricio Rosales-Rivera, Rodrigo Garcia-Lopez, Jose Esteban Munoz-Medina, Alejandro Sanchez-Flores, Alfredo Herrera-Estrella, Bruno Gomez-Gil, Nelly Selem Mojica, Angel Gustavo Salas-Lais, Joel Armando Vazquez-Perez, David Alejandro Cabrera-Gaytan, Larissa Fernandes-Matano, Luis Antonio Uribe-Noguez, Juan Bautista Chale-Dzul, Brenda Irasema Maldonado Meza, Fidencio Mejia-Nepomuceno, Rogelio Perez-Padilla, Rosa Maria Gutierrez-Rios, Antonio Loza, Benjamin Roche, Susana Lopez, Carlos F. Arias
Summary: This study presents the spread of the SARS-CoV-2 Omicron BA.1 subvariant in Mexico, which quickly replaced the Delta variant and caused the fourth COVID-19 surge in the country. The spread of BA.1 began in early December 2021 and became dominant within three weeks. Unlike previous variants, BA.1 did not exhibit a geographically distinct circulation pattern, but there were regional differences in the speed of replacing the Delta variant.
Article
Biotechnology & Applied Microbiology
Edgar Velastegui, Johan Quezada, Karlo Guerrero, Claudia Altamirano, Juan Andres Martinez, Julio Berrios, Patrick Fickers
Summary: Culture medium heterogeneity in industrial bioreactors leads to concentration gradients due to the loss of mixing efficiency. This study investigated the cell response to transient perturbations of high methanol concentration combined with hypoxia using a scale-down system. The results showed that stressful culture conditions affected cell metabolism, biomass formation, and cell flocculation. Surprisingly, these conditions actually benefited recombinant protein productivity by increasing the expression levels of genes and eGFP.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Infectious Diseases
Rodrigo Garcia-Lopez, Xaira Rivera-Gutierrez, Mauricio Rosales-Rivera, Selene Zarate, Jose Esteban Munoz-Medina, Benjamin Roche, Alfredo Herrera-Estrella, Bruno Gomez-Gil, Alejandro Sanchez-Flores, Blanca Taboada, Carlos F. Arias
Summary: The BW.1 and its descendant BW.1.1 variants emerged in Southeast Mexico and likely originated during the fifth wave of COVID-19 in July 2022. These variants share similar immune escape mutations with the BQ.1 variant, which may contribute to their rapid spread.
Review
Biotechnology & Applied Microbiology
Ricardo A. Gonzalez-Hernandez, Norma A. Valdez-Cruz, Martha L. Macias-Rubalcava, Mauricio A. Trujillo-Roldan
Summary: Terpenes and terpenoids are the largest group of natural products and secondary metabolites produced by living things. They are synthesized by enzymes called terpene synthases, which add functional groups to cyclized structures. Understanding the regulation of their synthesis is important for directing their production with desired pharmacological properties. This review covers the detailed study of the biosynthesis of fungal terpenoids and their regulation by various physiological and environmental factors.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Mechanics
Jessica Sanchez-Vargas, Francisco J. Valdes-Parada, Mauricio A. Trujillo-Roldan, Didier Lasseux
Summary: A closed macroscopic model for quasi-steady, inertial, incompressible, two-phase generalised Newtonian flow in rigid and homogeneous porous media is derived by upscaling the pore-scale equations. The derived model includes macroscopic equations for mass and momentum balance as well as an expression for the macroscopic pressure difference between the two fluid phases. The predictions from the upscaled models are in excellent agreement with direct numerical simulations, confirming the validity of the derived macroscopic models.
JOURNAL OF FLUID MECHANICS
(2023)
Article
Multidisciplinary Sciences
Otto Geiger, Alejandro Sanchez-Flores, Jonathan Padilla-Gomez, Mauro Degli Esposti
Summary: We breathe by using oxygen consumed by mitochondria in our cells to extract energy. Mitochondria, which derive from aerobic bacteria, play crucial roles in oxidative phosphorylation and other metabolic pathways in eukaryotic cells. The exact bacterial origin of mitochondria and their relationship to the aerobic metabolism of our cells is still controversial despite the abundance of genomic data. In this study, we employ various approaches to identify the most likely bacteria that are the living relatives of the ancestral bacteria from which mitochondria originated. These bacteria inhabit marine environments and possess a high frequency of aerobic traits as well as genes for the metabolism of essential lipids found in eukaryotic membranes, such as sphingolipids and cardiolipin.
Article
Engineering, Multidisciplinary
Norma A. Valdez-Cruz, Fernando Orozco-Sanchez, Mario Rodriguez-Monroy, Victor D. Busto, Mauricio A. Trujillo-Roldan
Summary: Biotechnology is an emerging field for developing countries, and bioreactors are crucial for the development and innovation of bioprocesses. An international training course on bioprocess scaling and bioreactor operation has been held to provide theoretical and practical training for the Latin American scientific community. The course has trained over 1400 people through lectures and 216 people with laboratory skills, and has created a network of contacts in consulting and people mobility.
REVISTA EDUCACION EN INGENIERIA
(2022)