Article
Biochemical Research Methods
Lauren T. Cordova, Hussain Dahodwala, Rebecca Cooley, Kelvin H. Lee
Summary: In this study, researchers evaluated the expression of five DNA repair genes in over 40 CHO cell lines and found a correlation between two genes and cell line stability. Additionally, they found a negative correlation between the expression levels of DNA repair genes and cell age.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Genetics & Heredity
Dylan G. Chitwood, Lisa Uy, Wanfang Fu, Stephanie R. Klaubert, Sarah W. Harcum, Christopher A. Saski
Summary: The accumulation of metabolic wastes in cell cultures can affect product quality, productivity, and trigger apoptosis. Researchers have attempted to address this issue in CHO cell cultures through various engineering approaches with varying levels of success. This study characterizes a recombinant CHO K-1 cell line adapted to high levels of extracellular lactate and explores the role of eccDNA and gene expression in the adaptation process. The findings suggest stochastic switching and alanine biosynthesis as potential stress adaptation mechanisms in CHO cells.
Article
Plant Sciences
Guillaume Besnard, Oceane Gorrilliot, Pauline Raimondeau, Benoit Genot, Ahmed El Bakkali, Fabien Anthelme, Djamel Baali-Cherif
Summary: The Laperrine's olive is a unique species in the Saharan Mountains, adapted to arid environments. Due to human pressures and limited natural regeneration, this species is locally endangered in the central Sahara. Understanding past population dynamics is crucial for defining management strategies.
Review
Biotechnology & Applied Microbiology
Tobias Jerabek, Christoph Keysberg, Kerstin Otte
Summary: This review highlights recent advances in cellular sub-transcriptomes, sub-proteomes, and secretome analyses for cell line development.
BIOTECHNOLOGY ADVANCES
(2022)
Review
Biotechnology & Applied Microbiology
Tobias Jerabek, Christoph Keysberg, Kerstin Otte
Summary: This review provides an overview of recent advances in the characterization of CHO cells (Chinese hamster ovary cells) using sub-omics approaches and their application in cell line development.
BIOTECHNOLOGY ADVANCES
(2022)
Article
Cell Biology
Sirin Saranyutanon, Srijan Acharya, Sachin Kumar Deshmukh, Mohammad Aslam Khan, Seema Singh, Ajay Pratap Singh
Summary: Nicotine induces M2 polarization of macrophages, enhancing their growth, motility, and invasion, potentially through the Src-STAT3 signaling axis. This novel role of nicotine in immunosuppression could be implicated in the pathogenesis of various diseases.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhipeng Huang, Arslan Habib, Guoping Zhao, Xiaoming Ding
Summary: This study successfully utilizes CRISPR-Cas9 technology to integrate foreign genes into a specific chromosomal location in Chinese hamster ovary cells, allowing for sustained and stable expression of exogenous proteins. The results demonstrate the advantage of the NC_048595.1 locus in this expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Juanjuan Luo, Ying Li, Tangxuan Zhang, Tianhan Xv, Chao Chen, Mengting Li, Qixiang Qiu, Yusheng Song, Shaogui Wan
Summary: Chemotherapy is commonly used for cancer treatment, but drug resistance is a major concern. The mechanisms of cancer drug resistance are complex and involve factors such as genomic instability, DNA repair, and chromothripsis. A recently emerged area of interest is extrachromosomal circular DNA (eccDNA), which forms due to genomic instability and chromothripsis. In this review, we summarize recent progress in understanding the role of eccDNA in the development of drug resistance and discuss its clinical applications and potential strategies for targeted cancer therapies.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Qinghao Zhang, Bo Jiang, Luke Nelson, Steven Huhn, Zhimei Du, Lawrence A. Chasin
Summary: CHO8A, a multiauxotrophic mutant of CHO-K1 cells, was created by restoring the prototrophy of the cells through transfection of complementary DNA-based genes. This cell line allows for the selection of transfectant clones with multiple polypeptide genes, as well as the single-step selection of high producers of a specific protein.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biodiversity Conservation
Lois Morel, Vincent Jung, Simon Chollet, Frederic Ysnel, Lou Barbe
Summary: The study proposes a new method to estimate dark diversity based on the co-occurrence of functional features. By comparing the taxonomic and functional dark diversity of recent woodlands and ancient forests, it shows clear differences in composition. Functional dark diversity provides novel perspectives for ecological diagnostic and restoration.
JOURNAL OF APPLIED ECOLOGY
(2022)
Article
Environmental Sciences
Johanna J. Geeson, Mark A. Hindell, Alistair J. Hobday, Cassie N. Speakman, John P. Y. Arnould
Summary: The Australian fur seal population is recovering but experiencing changing nutritional conditions, which may continue to decline under predicted climate change conditions.
FRONTIERS IN MARINE SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Tianyu Wu, Hao Gu, Yuxi Luo, Lei Wang, Qing Sang
Summary: Meiotic defects in mammalian oocytes can lead to abnormal chromosome segregation. Chromosome segregation is particularly error-prone in human oocytes, but the mechanisms behind these errors remain unclear. Recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis.
Article
Engineering, Electrical & Electronic
Arash Beiranvand, Paul Cuffe
Summary: This paper investigates the structural origins of congestion in power networks and proposes a method to alleviate congestion and improve grid loadability through the enhancement of shadow capacity. By introducing a new metric called shadow capacity, the paper identifies imbalances in line reactances and capacities as the cause of congestion. The results show a modest reduction in congestion, highlighting the potential value of optimizing power networks based on shadow capacity enhancement.
IEEE TRANSACTIONS ON POWER SYSTEMS
(2023)
Article
Environmental Sciences
J. S. Nanditha, Anuj Prakash Kushwaha, Rajesh Singh, Iqura Malik, Hiren Solanki, Dipesh Singh Chuphal, Swarup Dangar, Shanti Shwarup Mahto, Urmin Vegad, Vimal Mishra
Summary: The risk of floods in South Asia has increased due to high vulnerability and exposure. The August 2022 Pakistan flood demonstrates the magnitude and devastation that can occur under a warming climate. The flood was primarily driven by multiday extreme precipitation caused by two atmospheric rivers, resulting in significant human mortality and displacement. This event highlights the need for adaptation and climate mitigation in South Asia.
Review
Endocrinology & Metabolism
Lise Coderre, Lyna Debieche, Joelle Plourde, Remi Rabasa-Lhoret, Sylvie Lesage
Summary: Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis patients, with a prevalence of over 50% in adults. The etiology of CFRD is not fully understood, but research suggests it may result from beta-cell extrinsic factors. Inflammation and ductal cells near beta-cells could play a role in CFRD development.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Philipp N. Spahn, Xiaolin Zhang, Qing Hu, Huiming Lu, Nathaniel K. Hamaker, Hooman Hefzi, Shangzhong Li, Chih-Chung Kuo, Yingxiang Huang, Jamie C. Lee, Anthony J. Davis, Peter Ly, Kelvin H. Lee, Nathan E. Lewis
Summary: This study identified deleterious single-nucleotide variants in DNA repair genes in CHO cells, which contribute to productivity loss and genome instability. Correcting these DNA repair genes improves genome stability and protein expression in CHO cells.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Sumit K. Singh, Kelvin H. Lee
Summary: Glycosylation is a critical quality attribute of monoclonal antibody therapeutics. Hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) is a valuable technology for glycosylation characterization. Traditional glycan analysis based on glucose units (GU) and accurate mass (AM) is not suitable for complex samples or high-throughput applications. This study presents a two-step strategy for targeted glycan analysis and its application in different scenarios.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Nathaniel K. Hamaker, Lie Min, Kelvin H. Lee
Summary: The biomanufacturing industry is moving towards continuous processes, which may pose challenges due to fluctuations in host cell protein (HCP) levels. A study on Chinese hamster ovary (CHO) cells showed that HCP expression changes over time, but not as dramatically as originally expected.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Review
Chemistry, Applied
Alana C. Szkodny, Kelvin H. Lee
Summary: This review highlights the key milestones in the production of biopharmaceuticals and emphasizes the maturity of the technologies used and the importance of understanding the interaction between product quality and processing conditions.
ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Sandeep B. Kedia, Jeffrey C. Baker, Ruben G. Carbonell, Kelvin H. Lee, Christopher J. Roberts, John Erickson, John E. Schiel, Kelley Rogers, Gene Schaefer, Stefanie Pluschkell
Summary: The Manufacturing Readiness Levels (MRLs) are well-established tools for describing technology maturity, and the Biomanufacturing Readiness Levels (BRLs) provide a specific viewpoint for the biomanufacturing industry.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Young Hoon Oh, Matthew L. Becker, Kerri M. Mendola, Leila H. Choe, Lie Min, Kelvin H. H. Lee, Yinges Yigzaw, Alexander Seay, Jerome Bill, Xuanwen Li, David J. Roush, Steven M. Cramer, Stefano Menegatti, Abraham M. Lenhoff
Summary: In the production of biopharmaceuticals, the presence of residual host-cell proteins (HCPs) is a critical quality concern. Measurements on seven monoclonal antibody (mAb) processes revealed that HCP aggregates, not necessarily derived from chromatin, are important factors in the persistence of HCPs. These aggregates can also interfere with accurate detection of HCPs using proteomics methods. The study also highlights the difficulty in removing certain HCPs due to their functional complementarity to the biopharmaceutical product.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Lauren T. Cordova, Hussain Dahodwala, Kathryn S. Elliott, Jongyoun Baik, Daniel C. Odenewelder, Douglas Nmagu, Bradley A. Skelton, Lisa Uy, Stephanie R. Klaubert, Benjamin F. Synoground, Dylan G. Chitwood, Venkata Gayatri Dhara, Harnish Mukesh Naik, Caitlin S. Morris, Seongkyu Yoon, Michael Betenbaugh, Jon Coffman, Frank Swartzwelder, Michael Gilmeister, Sarah W. Harcum, Kelvin H. Lee
Summary: Due to the limitations in cell, media, and feed diversity, as well as the limited public availability of industrially relevant CHO cells, the knowledge translation and research progress in the field have been hindered. To address this issue, AMBIC has acquired two CHO reference cell lines from different lineages and developed detailed technology transfer protocols and a chemically defined media formulation, aiming to provide a universal and industrially relevant CHO culture platform.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Nathaniel. K. K. Hamaker, Kelvin. H. H. Lee
Summary: Efforts to improve CRISPR/Cas9 efficiency in targeted genomic modifications in mammalian cells led to the development of an all-in-one reporter system, including a new superfolder orange fluorescent protein (sfOrange), to quantify gene disruption, site-specific integration (SSI), and random integration (RI). Different donor plasmid formats and Cas9 nuclease variants were evaluated for accuracy and efficiency in Chinese hamster ovary cells. Double-cut and double-nick donor formats significantly improved targeting accuracy, and Cas9-mediated donor linearization increased RI events while donor nicking minimized RI without sacrificing SSI efficiency.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Review
Biotechnology & Applied Microbiology
Gene Schaefer, John Balchunas, Timothy Charlebois, John Erickson, Roger Hart, Sandeep B. Kedia, Kelvin H. Lee
Summary: The challenge of introducing new technologies into established industries is not unique to biopharmaceuticals, but it is crucial for the long-term competitiveness and delivery of therapies, particularly for new treatment modalities such as cell and gene therapies. This review identifies barriers to technology adoption and proposes enablers and suggestions for synergy and connection between innovation in product discovery and manufacturing, and across supplier, discovery, manufacturing, and regulatory arms.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
William Hilliard, Kelvin H. Lee
Summary: The use of targeted integration for industrial CHO cell line development requires significant upfront effort to identify genomic loci capable of supporting high therapeutic protein production. To address this barrier, the Transgene Integrated in Parallel screening method was used to characterize transgene expression from thousands of stable hotspots in the CHO genome. Cell lines with integrations at retargeted hotspot candidates consistently exhibited higher transgene mRNA expression than a commercially viable hotspot. These findings provide valuable resources for targeted integration platform development in the CHO community.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Chase E. Herman, Lie Min, Leila H. Choe, Ronald W. Maurer, Xuankuo Xu, Sanchayita Ghose, Kelvin H. H. Lee, Abraham M. Lenhoff
Summary: Recent research suggests that host-cell proteins (HCPs) and high molecular weight (HMW) species in monoclonal antibody downstream processing may be linked. Proteomic analysis reveals substantial overlap of HCP profiles between harvest cell culture fluid (HCCF) and protein A eluate, with HCPs conserved in aggregates that persist through the protein A capture step. These findings support previous hypotheses and highlight the importance of this persistence mechanism.
BIOTECHNOLOGY PROGRESS
(2023)
Article
Biotechnology & Applied Microbiology
Young Hoon Oh, Kerri M. Mendola, Leila H. Choe, Lie Min, Ashton R. Lavoie, Sobhana A. Sripada, Taufika Islam Williams, Kelvin H. Lee, Yinges Yigzaw, Alexander Seay, Jerome Bill, Xuanwen Li, David J. Roush, Steven M. Cramer, Stefano Menegatti, Abraham M. Lenhoff
Summary: This study investigates the characterization and persistence of host-cell proteins (HCPs) in downstream processing steps for monoclonal antibody (mAb) manufacturing. The results show variability in HCP identities during processing steps, but consistency in the most abundant HCPs across different processes. The abundance of HCPs is likely related to the reproducibility of quantification measurements, and certain groups of HCPs may hinder characterization. The study suggests that factors such as HCP abundance and mAb-HCP interactions contribute to the persistence of individual HCPs and the identification of common, persistent HCPs in mAb manufacturing.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Qiang Fu, Yong Suk Lee, Erica A. Green, Yongdan Wang, So Young Park, Ashli Polanco, Kelvin H. Lee, Michael Betenbaugh, David McNally, Seongkyu Yoon
Summary: This study investigated the influence of four process parameters on the quality attributes of rAAV products. Regression models and a design space were established, and the predictive capability of the models was confirmed.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemical Research Methods
Chase E. Herman, Lie Min, Leila H. Choe, Ronald W. Maurer, Xuankuo Xu, Sanchayita Ghose, Kelvin H. Lee, Abraham M. Lenhoff
Summary: Recent research has revealed that aggregates in mAb solutions may contain not only mAb oligomers but also hundreds of host-cell proteins (HCPs), which suggests a relationship between aggregate persistence and HCP clearance during downstream purification operations. This study found that the phenomenon is relevant to depth filtration, protein A chromatography, and flow-through anion-exchange (AEX) polishing. Confocal laser scanning microscopy showed that aggregates compete with mAb during protein A chromatography, and column chromatography confirmed the presence of high aggregate concentrations in the protein A elution tail. Similar observations were made in flow-through AEX chromatography, with aggregate retention depending on resin surface chemistry. The quantification of aggregate mass fraction may serve as a surrogate for informing early process development decisions regarding HCP clearance strategies.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Biochemical Research Methods
Lauren T. Cordova, Hussain Dahodwala, Rebecca Cooley, Kelvin H. Lee
Summary: In this study, researchers evaluated the expression of five DNA repair genes in over 40 CHO cell lines and found a correlation between two genes and cell line stability. Additionally, they found a negative correlation between the expression levels of DNA repair genes and cell age.
BIOTECHNOLOGY JOURNAL
(2023)
Review
Biochemical Research Methods
Pei-Ru Chen, Peng-Fei Xia
Summary: Carbon dioxide plays a crucial role in mitigating global climate change and supporting life on Earth. Synthetic biology and metabolic engineering offer a promising approach to enhance CO2 fixation by combining the advantages of autotrophic and heterotrophic organisms. This article reviews the current progress in constructing synthetic CO2 fixation pathways, discusses the underlying design principles and challenges, and provides insights into the future of carbon recycling through engineered synthetic carbon fixation pathways.
CURRENT OPINION IN BIOTECHNOLOGY
(2024)
