Biotechnology and Bioengineering最新文献_第2页

Demonstrating the Effectiveness of an Alternative to Triton X-100 for Detergent-Mediated Viral Inactivation in Biomanufacturing

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-02-05 DOI: 10.1002/bit.28940

Kakolie Banerjee, Alice Antonello, Sandra Johnson, Anja Licht, Almut Rapp, Corinne Miller

{"title":"Demonstrating the Effectiveness of an Alternative to Triton X-100 for Detergent-Mediated Viral Inactivation in Biomanufacturing","authors":"Kakolie Banerjee, Alice Antonello, Sandra Johnson, Anja Licht, Almut Rapp, Corinne Miller","doi":"10.1002/bit.28940","DOIUrl":"https://doi.org/10.1002/bit.28940","url":null,"abstract":"Detergent-mediated viral inactivation is an important process step for ensuring viral safety of parenteral biotherapeutics, including plasma proteins and monoclonal antibodies (mAb). The conventional Triton X-100 detergent has ecological toxicity concerns and REACH classification that mandate replacement in the biopharmaceutical industry. Criteria for a replacement detergent include viral inactivation efficacy, acceptable safety and biodegradation profile, process removal, and quality suitable for parenteral drug product manufacturing. A non-ionic, C11-15 secondary alcohol ethoxylate, Deviron 13-S9 detergent, has been demonstrated to meet the necessary requirements for detergent performance. Benchmarking studies with Triton X-100 detergent demonstrate comparable performance with a panel of enveloped viruses in multiple matrices, including human IgG, clarified cell culture harvest, and fractionated plasma. Deviron 13-S9 detergent demonstrated viral inactivation efficiency comparable to or better than Triton X-100 detergent, achieving > 5 log reduction values. Critical micelle concentration was determined across different temperatures and media. Deviron 13-S9 detergent was demonstrated to be readily biodegradable according to OECD 301B guidelines. The absence of detergent binding to typical chromatography resins used in downstream purification was confirmed. The process removal of Deviron 13-S9 detergent from a protein-containing matrix was demonstrated using a protein A resin. These findings support Deviron 13-S9 detergent as a viable alternative to Triton X-100 detergent, ensuring robust viral inactivation, environmental compatibility, and alignment with regulatory requirements.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"37 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromatography in Downstream Processing of Recombinant Adeno-Associated Viruses: A Review of Current and Future Practises

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-02-04 DOI: 10.1002/bit.28932

Julius Klemens Lorek, Madelène Isaksson, Bernt Nilsson

{"title":"Chromatography in Downstream Processing of Recombinant Adeno-Associated Viruses: A Review of Current and Future Practises","authors":"Julius Klemens Lorek, Madelène Isaksson, Bernt Nilsson","doi":"10.1002/bit.28932","DOIUrl":"https://doi.org/10.1002/bit.28932","url":null,"abstract":"Recombinant adeno-associated virus (rAAV) has emerged as an attractive gene delivery vector platform to treat both rare and pervasive diseases. With more and more rAAV-based therapies entering late-stage clinical trials and commercialization, there is an increasing pressure on the rAAV manufacturing process to accelerate drug development, account for larger trials, and commercially provide high doses. Still, many of the pre-clinical and clinical manufacturing processes are tied to outdated technologies, which results in substantial production expenses. Those processes face challenges including low productivity and difficult scalability, which limits its ability to provide for required dosages which in turn influences the accessibility of the drug. And as upstream efforts are expected to increase productivities, the downstream part needs to adapt with more scalable and efficient technologies. In this review, both traditional and novel rAAV downstream technologies are presented and discussed. Traditional rAAV downstream processes are based on density gradient ultracentrifugation and have been shown to effectively purify rAAVs with high yields and purities. However, those processes lack scalability and efficiency, which is why novel rAAV downstream processes based on column-chromatography have emerged as an attractive alternative and show potential for integration in continuous processes, following the principle of next-generation manufacturing.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"8 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Air Temperature on Transient Expression of Influenza Hemagglutinin in Nicotiana benthamiana: Analysis of Transgene Transcription and Plant Stress Responses.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-31 DOI: 10.1002/bit.28942

Patthasarun Pruksarojanakul, Kazune Atsumi, Youngjun Oh, Nobuyuki Matoba, Ryo Matsuda

{"title":"Effects of Air Temperature on Transient Expression of Influenza Hemagglutinin in Nicotiana benthamiana: Analysis of Transgene Transcription and Plant Stress Responses.","authors":"Patthasarun Pruksarojanakul, Kazune Atsumi, Youngjun Oh, Nobuyuki Matoba, Ryo Matsuda","doi":"10.1002/bit.28942","DOIUrl":"https://doi.org/10.1002/bit.28942","url":null,"abstract":"Postinfiltration air temperature is known to affect the accumulation of recombinant protein in Agrobacterium-mediated transient expression in Nicotiana benthamiana plants, including the number of days needed to reach maximum content and the rate of reduction thereafter. This study aimed to clarify whether the transcript levels of the transgenes and those of plant stress response markers (i.e., hypersensitive response and endoplasmic reticulum [ER] stress) could be primary determinants of the accumulation of recombinant influenza hemagglutinin (HA) at 21 or 26°C. We found no correlation between the transgene expression levels (HA, RdRP, and MP) and the number of days needed to reach the maximum HA protein content at both temperatures. Regardless of the accumulation compartment, HA protein content peaked earlier at 26°C than at 21°C. The rapid reduction of HA content after reaching the maximum, observed only in the ER at 26°C, correlated with severe necrosis and high transcript levels of two representative ER stress markers, bZIP60 and BiP. This correlation suggests that high postinfiltration air temperature affects HA accumulation primarily through ER stress, a key factor in the rapid reduction of HA content after the peak.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine Learning-Powered Optimization of a CHO Cell Cultivation Process.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-31 DOI: 10.1002/bit.28943

Jannik Richter, Qimin Wang, Ferdinand Lange, Phil Thiel, Nina Yilmaz, Dörte Solle, Xiaoying Zhuang, Sascha Beutel

{"title":"Machine Learning-Powered Optimization of a CHO Cell Cultivation Process.","authors":"Jannik Richter, Qimin Wang, Ferdinand Lange, Phil Thiel, Nina Yilmaz, Dörte Solle, Xiaoying Zhuang, Sascha Beutel","doi":"10.1002/bit.28943","DOIUrl":"https://doi.org/10.1002/bit.28943","url":null,"abstract":"Chinese Hamster Ovary (CHO) cells are the most widely used cell lines to produce recombinant therapeutic proteins such as monoclonal antibodies (mAbs). However, the optimization of the CHO cell culture process is very complex and influenced by various factors. This study investigates the use of machine learning (ML) algorithms to optimize an established industrial CHO cell cultivation process. A ML algorithm in the form of an artificial neural network (ANN) was used and trained on datasets from historical and newly generated CHO cell cultivation runs. The algorithm was then used to find better cultivation conditions and improve cell productivity. The selected artificial intelligence (AI) tool was able to suggest optimized cultivation settings and new condition combinations, which promised both increased cell growth and increased mAb titers. After performing the validation experiments, it was shown that the ML algorithm was able to successfully optimize the cultivation process and significantly improve the antibody production. The best results showed an increase in final mAb titer up to 48%, demonstrating that the use of ML algorithms is a promising approach to optimize the productivity of bioprocesses like CHO cell cultivation processes clearly.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling the Performance of an Anaerobic Moving Bed Biofilm Reactor.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-31 DOI: 10.1002/bit.28938

Yuhang Cai, Joshua P Boltz, Bruce E Rittmann

{"title":"Modeling the Performance of an Anaerobic Moving Bed Biofilm Reactor.","authors":"Yuhang Cai, Joshua P Boltz, Bruce E Rittmann","doi":"10.1002/bit.28938","DOIUrl":"https://doi.org/10.1002/bit.28938","url":null,"abstract":"Sub-models representing transformation processes by microorganisms and hydrolases, a one-dimensional (1-D) biofilm, and a bioreactor were integrated to simulate organic-matter fermentation and methane (CH4) production in an anaerobic moving bed biofilm reactor (AnMBBR). The integrated models correctly represented all experimental observations and identified mechanisms underlying how and why AnMBBR performance changed when the volumetric loading rate (VLR) of total chemical oxygen demand (TCOD) increased from 3.9 to 19.5 kg CODT/m3-d. The fractional removal of TCOD and CH4 production decreased as the VLR of TCOD increased, in part, due to an increasing biofilm thickness that filled the protected channels in the interior of the plastic carriers and led to a decrease in biofilm surface area and an increase in the mass-transfer boundary layer. Also, the ~25-day duration for each VLR of TCOD was too brief to allow the biofilm to establish a new quasi-steady state with respect to biofilm thickness. The mechanistic understanding of how biofilm characteristics and process performance respond to increased VLR of TCOD can be applied in engineering practice to improve AnMBBR process design and operation.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

pH Threshold Impacts Chalcopyrite Bioleaching Dynamics for the Extreme Thermoacidophile Sulfurisphaera ohwakuensis.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-31 DOI: 10.1002/bit.28945

Daniel J Willard, Mohammad J H Manesh, Kaitlyn M John, Robert M Kelly

{"title":"pH Threshold Impacts Chalcopyrite Bioleaching Dynamics for the Extreme Thermoacidophile Sulfurisphaera ohwakuensis.","authors":"Daniel J Willard, Mohammad J H Manesh, Kaitlyn M John, Robert M Kelly","doi":"10.1002/bit.28945","DOIUrl":"https://doi.org/10.1002/bit.28945","url":null,"abstract":"The extremely thermoacidophilic archaeon Sulfurisphaera ohwakuensis served as the basis for probing how initial pH (pHinitial) affects copper mobilization from chalcopyrite. Screening of small-scale cultures (75 mL) at 75°C revealed that ~pH 3.0 was a maximal threshold for bioleaching onset. Subsequently, chalcopyrite at 10 g/L in 750 mL culture media, containing small amounts of ferric ion, adjusted to pH 2.5 with sulfuric acid and incubated for 24 h at 75°C before inoculation, brought the pH to approximately 3.0 through abiotic chemical reactions. However, the resulting subtle differences in pHinitial (3.0 ± 0.15) in bioleaching cultures, while not affecting microbial growth, were critical to bioleaching onset and progress. Initial iron levels were less important than pHinitial in starting the bioleaching process. X-Ray Diffraction (XRD) surface analysis informed bioleaching trajectories over 21 days and reinforced the impact of pHinitial. The subtle differences in pHinitial markedly affected S. ohwakuensis onset and outcomes, as it presumably would for other bioleaching thermoacidophilic archaea. Furthermore, the findings here highlight the challenges faced in replicating bioleaching experiments across, and even within, laboratories as well as in achieving consistent results in bioleaching processes.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alterations in Protein Phosphorylation and Arginine Biosynthesis Metabolism Confer β-Phenylethanol Tolerance in Saccharomyces cerevisiae.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-30 DOI: 10.1002/bit.28936

Chenghan Yang, Yilin Ren, Li Zhang, Yina Li, Chunxia Wang, Haifeng Hang, Xiwei Tian, Ali Mohsin, Ju Chu, Yingping Zhuang

{"title":"Alterations in Protein Phosphorylation and Arginine Biosynthesis Metabolism Confer β-Phenylethanol Tolerance in Saccharomyces cerevisiae.","authors":"Chenghan Yang, Yilin Ren, Li Zhang, Yina Li, Chunxia Wang, Haifeng Hang, Xiwei Tian, Ali Mohsin, Ju Chu, Yingping Zhuang","doi":"10.1002/bit.28936","DOIUrl":"https://doi.org/10.1002/bit.28936","url":null,"abstract":"The aromatic compound β-phenylethanol (2-PE) is inherently toxic and can inhibit cell activity in Saccharomyces cerevisiae, making it highly challenging to enhance strain tolerance through rational design due to the lack of reliable connections between tolerance phenotype and genetic loci. This study employed adaptive laboratory evolution strategy to investigate the tolerance characteristics of S. cerevisiae S288C under inhibitory concentrations of 2-PE. The tolerant mutant SEC4.0 was characterized through comprehensive analysis of whole genome sequence, transcriptome, and phosphoproteome. The findings revealed that the high resistance of SEC4.0 was not primarily due to large-scale transcriptional upregulation of stress response genes, but rather through alterations in the phosphorylation levels of lipid-related pathways. PKC1 mutations that affect stress signal transduction and SPT3 mutations that affect arginine biosynthesis have been shown to significantly enhance 2-PE resistance. This study also investigated the effects of exogenous amino acid addition and synergistic effects with two key mutanted genes on 2-PE resistance. This study provides a foundation for enhancing yeast tolerance to this aromatic compound through rational design strategies.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Modeling Approach for Predicting the Growth of Filamentous Algae in Outdoor Algae-Based Wastewater Treatment Systems.

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-30 DOI: 10.1002/bit.28941

Sulochana Pitawala, Peter J Scales, Gregory J O Martin

{"title":"A New Modeling Approach for Predicting the Growth of Filamentous Algae in Outdoor Algae-Based Wastewater Treatment Systems.","authors":"Sulochana Pitawala, Peter J Scales, Gregory J O Martin","doi":"10.1002/bit.28941","DOIUrl":"https://doi.org/10.1002/bit.28941","url":null,"abstract":"Filamentous algae (FA) can form readily harvestable floating mats or attached turfs that facilitate their application in wastewater treatment systems. However, large-scale implementation is hindered by our inability to predict performance as a function of key operational parameters. A predictive mathematical model would be a valuable tool for designing efficient FA-based systems. Developing accurate models is challenging due to dynamic environmental conditions and the spatial complexities of FA cultures. In this work, a model was developed to mathematically describe the biomass productivity of static FA cultures (mats and turfs) in relation to the incident light intensity and temperature. The model was validated against published data to investigate the influence of time-dependent inhibition (inhibition from sustained light exposure) on productivity. When time-dependent inhibition was included in the model, predictions were within ~10% of experimental values, however, without including time-dependent inhibition there was a sixfold overestimation of biomass productivity. The model could also generate predictions of the effects of time-dependent inhibition during diurnal light fluctuations using experimentally determined rate constants. The model represents a powerful tool for optimizing the design and operational parameters in FA cultures that could be further expanded to incorporate the influence of nutrient and CO2 availability.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effectively Guiding Cell Elongation and Alignment by Constructing Micro/Nano Hierarchical Patterned Titania on Titanium Substrate

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-29 DOI: 10.1002/bit.28934

Feng-Jiao Bai, Hui Wang, Yu-Qing Hu, Yun-Fei Shao, Yi-Ran Zhu, Yu-Lin Jiang, Jian-Chen Hu, Hui-Jing Zhao, Ke-Qin Zhang

{"title":"Effectively Guiding Cell Elongation and Alignment by Constructing Micro/Nano Hierarchical Patterned Titania on Titanium Substrate","authors":"Feng-Jiao Bai, Hui Wang, Yu-Qing Hu, Yun-Fei Shao, Yi-Ran Zhu, Yu-Lin Jiang, Jian-Chen Hu, Hui-Jing Zhao, Ke-Qin Zhang","doi":"10.1002/bit.28934","DOIUrl":"https://doi.org/10.1002/bit.28934","url":null,"abstract":"Based on the innate sensitivity of cell to substrate topographical cues, modulating cell-directed growth behavior is crucial for promoting tissue repair and reconstruction. Although photolithography technology has been extensively employed to fabricate a variety of anisotropic patterned structures to guide cell growth, it remains a great challenge to design high-resolution micro/nano hierarchical structures directly onto medical titanium (Ti)-based implants. Herein, we present a rapid, reliable and reproducible approach combining photolithography and hydrothermal technology to construct a micro/nano hierarchical structure including anisotropic micro-strips and a porous structure composed of TiO2 nanotubes features. In vitro biological and physicochemical analyses revealed that the micro/nano hierarchical structures not only efficiently facilitate the localization and adsorption of BSA molecules, but also enhances the control of cell growth behavior. The synergistic effect between the physical limitation for organizing cellular cytoskeleton at micropattern and the control of focal adhesion sits at the nanoscale can effectively guide cells to maintain stable elongation and alignment, even at large micro-stripe width of 100 μm. This study presents a promising strategy to precisely construct micro/nano multi-level patterned structure on Ti substrate using biomaterials with excellent biocompatibility. These functional micro/nano hybrid micropatterns offer a powerful platform for regulating bioreagent localization and cell behaviors in various applications including tissue engineering, regenerative medicine, drug screening, and biosensors.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"48 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteo-Transcriptomic Analysis Reveals the Mechanisms Underlying Escherichia coli Phenotypic Shifts Under Blue Light

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-01-28 DOI: 10.1002/bit.28939

Shuqi Shi, Wenlu Qi, Jinming Zhang, Caice Liang, Wei Liu, Hui Han, Wei Zhuang, Tianpeng Chen, Wenjun Sun, Yong Chen

引用次数: 0