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A design space for the filtration of challenging monoclonal antibodies using Planova™ S20N, a new regenerated cellulose virus removal filter.
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2025-01-23 DOI: 10.1002/btpr.3533
Asami Inoue, Satoshi Murakami, Akika Futamura, Naoto Watanabe, Yumiko Masuda
{"title":"A design space for the filtration of challenging monoclonal antibodies using Planova™ S20N, a new regenerated cellulose virus removal filter.","authors":"Asami Inoue, Satoshi Murakami, Akika Futamura, Naoto Watanabe, Yumiko Masuda","doi":"10.1002/btpr.3533","DOIUrl":"https://doi.org/10.1002/btpr.3533","url":null,"abstract":"<p><p>Virus removal by filtration is a crucial step in ensuring the safety of therapeutic antibodies and other biopharmaceutical products by mitigating the risk of endogenous and adventitious viral contamination. However, there are monoclonal antibodies (mAb) that are difficult to filter effectively using virus removal filters (i.e., challenging mAbs), necessitating the creation of guidelines for designing suitable filtration conditions for these challenging molecules. This study presents a filtration design space for filtration conditions using a new regenerated cellulose membrane filter with a representative challenging mAb. The filter demonstrated that filtration throughput is adaptable across a wide range of conditions for low to medium mAb concentrations, indicating its suitability for introduction into platform processes for related biopharmaceutical products.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3533"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Highly iterated palindrome 1 sequence improves Synechococcus sp. PCC 7002 transformation efficiencies in a homology- and methylation-dependent manner.
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2025-01-23 DOI: 10.1002/btpr.3518
Cody Kamoku, David R Nielsen
{"title":"Highly iterated palindrome 1 sequence improves Synechococcus sp. PCC 7002 transformation efficiencies in a homology- and methylation-dependent manner.","authors":"Cody Kamoku, David R Nielsen","doi":"10.1002/btpr.3518","DOIUrl":"https://doi.org/10.1002/btpr.3518","url":null,"abstract":"<p><p>The ability to precisely engineer cyanobacterial metabolism first requires the ability to efficiently deliver engineered DNA constructs. Here, we investigate how natural transformation efficiencies in Synechococcus sp. PCC 7002 can be greatly improved by leveraging the native and abundant cyanobacterial Highly Iterated Palindrome 1 (HIP1) sequence. While including at least one homologous HIP1 site within the homology arms of an integrating plasmid increased integration efficiency by up to 7-fold, methylation of those sites by HIP1 methyltransferase (encoded by slr0214 from Synechococcus sp. PCC 6803) boosted this to greater than a 100-fold improvement overall. Non-homologous HIP1 sites also improved transformation efficiencies of both integrating and replicating episomal plasmids (by up to 60- and 9-fold, respectively), but only if methylated. The collective data further reveal that HIP1 does not function as part of a native restriction enzyme system in PCC 7002, but rather may improve transformation efficiency via an alternative mechanism(s), occurring prior to and/or during homologous recombination. Future studies are needed, however, to more clearly elucidate the specific role of HIP1 during natural transformation of cyanobacteria.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3518"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Sensitivity of bulk electrical impedance spectroscopy (bio-capacitance) probes to cell and culture properties: Study on CHO cell cultures. 体电阻抗谱(生物电容)探针对细胞和培养特性的敏感性:CHO细胞培养的研究。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-12-26 DOI: 10.1002/btpr.3519
Elham Salimi, Sara Absalan, Julien Robitaille, Johnny Montes, Michael Butler, Douglas Thomson, Greg Bridges
{"title":"Sensitivity of bulk electrical impedance spectroscopy (bio-capacitance) probes to cell and culture properties: Study on CHO cell cultures.","authors":"Elham Salimi, Sara Absalan, Julien Robitaille, Johnny Montes, Michael Butler, Douglas Thomson, Greg Bridges","doi":"10.1002/btpr.3519","DOIUrl":"https://doi.org/10.1002/btpr.3519","url":null,"abstract":"<p><p>Bulk electrical impedance spectroscopy (bio-capacitance) probes, hold significant promise for real-time cell monitoring in bioprocesses. Focusing on Chinese hamster ovary (CHO) cells, we present a sensitivity analysis framework to assess the impact of cell and culture properties on the complex permittivity spectrum, ε<sub>mix</sub>, and its associated parameters, permittivity increment, Δε, critical frequency, f<sub>c</sub>, and Cole-Cole parameter, α, measured by bio-capacitance probes. Our sensitivity analysis showed that Δε is highly sensitive to cell size and concentration, making it suitable for estimating biovolume during the exponential growth phase, whereas f<sub>c</sub> provides information about cumulative changes in cell size, membrane permittivity, and cytoplasm conductivity during the transition to death phase. The analysis indicated that specific information about cell membrane permittivity or internal conductivity cannot be extracted from ε<sub>mix</sub> spectrum. Based on the sensitivity analysis, we proposed two alternative parameters for monitoring cells in bioprocesses: Δε<sub>1 MHz</sub> and Δε<sub>1 MHz</sub>/Δε<sub>0.3 MHz</sub>, using measurements at 300 kHz, 1 MHz, and 10 MHz. Δε<sub>1 MHz</sub> is suitable for estimating viable cell density during the exponential growth phase due to its lower sensitivity to cell size. Δε<sub>1 MHz</sub>/Δε<sub>0.3 MHz</sub> can replace f<sub>c</sub> due to similar sensitivities to cell size and dielectric properties. These frequencies are within most bio-capacitance probes' optimal operation range, eliminating the need for low-frequency electrode polarization and high-frequency stray capacitances corrections. Experimental measurements on CHO cells confirmed the results of sensitivity analysis.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3519"},"PeriodicalIF":2.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Online monitored characterization of Phocaeicola vulgatus for organic acid production using anaerobic microtiter plate cultivations. 利用厌氧微孔板培养在线监测 Phocaeicola vulgatus 生产有机酸的特征。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-12-20 DOI: 10.1002/btpr.3526
Laura Keitel, Benjamin Schick, Gino Pohen, Stanislav Yordanov, Jochen Büchs
{"title":"Online monitored characterization of Phocaeicola vulgatus for organic acid production using anaerobic microtiter plate cultivations.","authors":"Laura Keitel, Benjamin Schick, Gino Pohen, Stanislav Yordanov, Jochen Büchs","doi":"10.1002/btpr.3526","DOIUrl":"https://doi.org/10.1002/btpr.3526","url":null,"abstract":"<p><p>Phocaeicola vulgatus (formerly Bacteroides vulgatus), an anaerobic gut bacterium, produces several organic acids. Research on P. vulgatus is still in its infancy. However, a detailed understanding of P. vulgatus growth and metabolism is essential for its assessment as an organic acid producer. Media variations, including different initial glucose and NH<sub>4</sub>Cl concentrations and osmolalities, are significant means to yield higher organic acid titers. Furthermore, examining different nitrogen and carbon sources is important to evaluate the potential of P. vulgatus for growth on renewable resources. Cultivations were performed in an in-house built device for anaerobic online-monitoring of fluorescence and scattered light in microtiter plates. Results revealed that the highest organic acid concentrations were reached while using galactose, glucose, or xylose as a carbon source, high osmolalities, and 0.25 g L<sup>-1</sup> NH<sub>4</sub>Cl. In addition, the organic acid composition changed with changing carbon and nitrogen sources. P. vulgatus was successfully further characterized, thereby contributing to a faster characterization of other anaerobic strains and paving the way for anaerobic organic acid production.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3526"},"PeriodicalIF":2.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
High-sensitivity real-time monitoring of pH and respiration activity unveils metabolic dynamics in shake flask cultures. 高灵敏度实时监测pH值和呼吸活动揭示了摇瓶培养的代谢动力学。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-12-13 DOI: 10.1002/btpr.3525
Burak Sarikaya, Karsten Günster, Luca Antonia Grebe, Eva Forsten, Katharina Hürter, Jochen Büchs, Jørgen Magnus
{"title":"High-sensitivity real-time monitoring of pH and respiration activity unveils metabolic dynamics in shake flask cultures.","authors":"Burak Sarikaya, Karsten Günster, Luca Antonia Grebe, Eva Forsten, Katharina Hürter, Jochen Büchs, Jørgen Magnus","doi":"10.1002/btpr.3525","DOIUrl":"https://doi.org/10.1002/btpr.3525","url":null,"abstract":"<p><p>Erlenmeyer shake flasks are widely used during the first steps of bioprocess development. Despite their broad application in academia and industry, shake flasks usually lack standardized and user-friendly online monitoring techniques. In this work, the pH and Respiratory Activity MOnitoring System (pH-RAMOS) for the non-invasive online measurement of the oxygen transfer rate (OTR), carbon dioxide transfer rate (CTR), and pH in up to eight parallel shake flasks under sterile conditions is presented. The OTR and CTR are quasi-continuously measured in the headspace of the shake flasks using dedicated oxygen and carbon dioxide sensors, enabling precise respiratory quotient (RQ) evaluation. Self-adhesive pH sensor spots are used for the high-frequent real-time pH monitoring of the culture. These prototype pH sensor spots stand out due to their simple sterilizability and subsequent one-point calibration in the cultivation medium. The long-term stability of the pH sensor spots was assessed in a 28-day long abiotic experiment. The novel pH-RAMOS was validated with different eukaryotic and prokaryotic microorganisms, such as Ogataea polymorpha, Ustilago trichophora, and Vibrio natriegens. The combination of online OTR, CTR, RQ, and pH signals allowed for identifying various metabolic phenomena, such as oxygen limitations, substrate limitations, diauxies, and the production or consumption of specific compounds, based on their degree of reduction or change of pH. The high-frequent and sensitive pH-monitoring was particularly advantageous for registering subtle and transient metabolic phenomena.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3525"},"PeriodicalIF":2.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Electrospun gelatin/hyaluronic acid nanofibers as a platform for uric acid delivery to neural tissue. 电纺明胶/透明质酸纳米纤维作为向神经组织输送尿酸的平台。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-11-10 DOI: 10.1002/btpr.3517
Reva M Street, Frank H Kung, Laura T Beringer, Daniel B Amchin, Bonnie L Firestein, Caroline L Schauer
{"title":"Electrospun gelatin/hyaluronic acid nanofibers as a platform for uric acid delivery to neural tissue.","authors":"Reva M Street, Frank H Kung, Laura T Beringer, Daniel B Amchin, Bonnie L Firestein, Caroline L Schauer","doi":"10.1002/btpr.3517","DOIUrl":"https://doi.org/10.1002/btpr.3517","url":null,"abstract":"<p><p>Uric acid (UA) is an antioxidant that has been reported to be a neuroprotective compound for injuries and diseases, and specifically, diseases of the central nervous system. However, uric acid is highly insoluble in aqueous solutions, and high levels in the serum lead to gout, which limits its use in humans. Here, we develop a novel drug delivery platform that will release uric acid in a sustained manner for application to neural tissue. We demonstrate that one-step incorporation of UA into an electrospun gelatin/hyaluronic acid nanofiber mat results in controlled release of UA in culture medium. Taking a unique approach, we made solutions of 12% gelatin and 1% hyaluronic acid in a formic acid solvent and added UA for production of nanofiber mats. We then dehydrothermally crosslinked the mats and tested for release of UA into physiological cell culture medium. To test whether the mats have any detrimental effects on healthy nervous system tissue, we cultured spinal cord explants on the mats extended and assessed extensions from the explants. We observed that comparable numbers and lengths of dendrites are extended from the spinal cord tissue, regardless of the amount UA content in the mats. Our results suggest that electrospun gelatin/hyaluronic acid nanofibers can be used as a platform for sustained uric acid delivery to neural tissue without detrimental effects.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3517"},"PeriodicalIF":2.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Non-thermal plasma decontamination of microbes: a state of the art. 微生物的非热等离子净化:最新技术。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-10-27 DOI: 10.1002/btpr.3511
Yiyi Xu, Amarjeet Bassi
{"title":"Non-thermal plasma decontamination of microbes: a state of the art.","authors":"Yiyi Xu, Amarjeet Bassi","doi":"10.1002/btpr.3511","DOIUrl":"https://doi.org/10.1002/btpr.3511","url":null,"abstract":"<p><p>Microbial decontamination is a critical concern in various sectors, from healthcare to food processing. Traditional decontamination methods, while effective to a degree, present limitations in terms of environmental impact, efficiency, and potential harm to the target material. This review investigates the emerging realm of non-thermal plasma (NTP) as a promising alternative for microbial decontamination, emphasizing its mechanisms, reactor designs and applications. The mechanism decomposed into physical, chemical and biological effects of plasma, are elaborated upon to provide a foundational understanding of the intrinsic principles of plasma decontamination. Except for the generation type of NTP, reactors and other parameters by which NTP achieves microbial decontamination, emphasizing the design considerations and parameters that influence its efficacy. Moreover, the latest applications of NTP in decontaminating air, water, and surfaces, supported by the latest research findings in each domain are explored. Additionally, the perspectives on the future research tendencies of NTP decontamination and disinfection are highlighted with potential avenues for exploration and innovation. Through this comprehensive review, the aim is to underscore the potential of NTP, particularly DBD plasma, as a versatile, efficient, and environmentally friendly method for microbial decontamination.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3511"},"PeriodicalIF":2.5,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Mechanistic model of minute virus of mice elution behavior in anion exchange chromatography purification. 阴离子交换色谱纯化过程中小鼠微小病毒洗脱行为的机理模型。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-10-23 DOI: 10.1002/btpr.3516
Ryunosuke Kitamura, Lena Enghauser, Riku Miyamoto, Takahiro Ichikawa, Takaki Aiso, Yumiko Masuda, Daisuke Kajihara, Hirofumi Kakihara, Koichi Nonaka
{"title":"Mechanistic model of minute virus of mice elution behavior in anion exchange chromatography purification.","authors":"Ryunosuke Kitamura, Lena Enghauser, Riku Miyamoto, Takahiro Ichikawa, Takaki Aiso, Yumiko Masuda, Daisuke Kajihara, Hirofumi Kakihara, Koichi Nonaka","doi":"10.1002/btpr.3516","DOIUrl":"https://doi.org/10.1002/btpr.3516","url":null,"abstract":"<p><p>This study aimed to propose a methodology for developing a mechanistic model for viral clearance of the minute virus of mice (MVM) on flow-through anion exchange (AEX) chromatography. Protein surface analysis was applied to investigate the possibility of molecular interaction between the recombinant biotherapeutic and MVM. The protein product-free Tris buffers were spiked with MVM, and the MVM elution profile from AEX chromatography was quantitatively analyzed using quantitative polymerase chain reaction (qPCR) for pooled fractions. GoSilico™ Chromatography Modeling Software was applied to develop the mechanistic models for MVM species. For evaluating the visual fit of the developed model, the R<sup>2</sup> of intact MVM virions and uncoated capsids between the simulated and measured amount in each fraction are 0.880 and 0.948, respectively. Response surface plots of logarithmic reduction values (LRV) against pH and conductivity in loaded sample were generated to show the range for suitable loaded sample conditions for achieving a good LRV. To evaluate the applicability of the developed MVM elution model to a recombinant biotherapeutic, two demonstrations of AEX chromatography purification were performed with a loaded sample of a model monoclonal antibody. The peaks of the MVM species in the elution step of both runs were accurately simulated by the developed model. In addition, to assess the possibility of molecular interaction between the virus and the target protein significantly affecting the MVM elution behavior, the antibody's surface was evaluated in terms of hydrophobicity/hydrophilicity using surface analysis.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3516"},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Comparing in silico flowsheet optimization strategies in biopharmaceutical downstream processes. 比较生物制药下游工艺中的硅学流程优化策略。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-10-18 DOI: 10.1002/btpr.3514
Daphne Keulen, Myrto Apostolidi, Geoffroy Geldhof, Olivier Le Bussy, Martin Pabst, Marcel Ottens
{"title":"Comparing in silico flowsheet optimization strategies in biopharmaceutical downstream processes.","authors":"Daphne Keulen, Myrto Apostolidi, Geoffroy Geldhof, Olivier Le Bussy, Martin Pabst, Marcel Ottens","doi":"10.1002/btpr.3514","DOIUrl":"https://doi.org/10.1002/btpr.3514","url":null,"abstract":"<p><p>The challenging task of designing biopharmaceutical downstream processes is initially to select the type of unit operations, followed by optimizing their operating conditions. For complex flowsheet optimizations, the strategy becomes crucial in terms of duration and outcome. In this study, we compared three optimization strategies, namely, simultaneous, top-to-bottom, and superstructure decomposition. Moreover, all strategies were evaluated by either using chromatographic Mechanistic Models (MMs) or Artificial Neural Networks (ANNs). An overall evaluation of 39 flowsheets was performed, including a buffer-exchange step between the chromatography operations. All strategies identified orthogonal structures to be optimal, and the weighted overall performance values were generally consistent between the MMs and ANNs. In terms of time-efficiency, the decomposition method with MMs stands out when utilizing multiple cores on a multiprocessing system for simulations. This study analyses the influence of different optimization strategies on flowsheet optimization and advices on suitable strategies and modeling techniques for specific scenarios.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3514"},"PeriodicalIF":2.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
General strategies for IgG-like bispecific antibody purification. IgG 样双特异性抗体纯化的一般策略。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2024-10-15 DOI: 10.1002/btpr.3515
Yifeng Li
{"title":"General strategies for IgG-like bispecific antibody purification.","authors":"Yifeng Li","doi":"10.1002/btpr.3515","DOIUrl":"https://doi.org/10.1002/btpr.3515","url":null,"abstract":"<p><p>Bispecific antibodies (bsAbs) can simultaneously bind two different antigens or epitopes. Their dual-targeting capability enables novel mechanisms of action, gaining therapeutic advantages over conventional monospecific mAbs. In recent years, the number of bsAbs grows rapidly and bsAbs under development are available in diverse formats. In particular, Fc-containing IgG-like bsAbs, which represent the major group, can be constructed in asymmetric or symmetric format. For asymmetric ones, whose assembly requires multiple distinct chains, although numerous strategies have been developed to promote desired chain pairing, product-related variants such as free chains, half molecules and mispaired species are usually present at various levels. For symmetric ones, increased level of aggregates and truncating variants is often associated with their production. In general, bsAbs pose greater challenges to the downstream team than regular mAbs. In the past few years, our team successfully developed the downstream process for over 70 bsAbs in greater than 30 different formats and accumulated substantial experience. This review introduces general strategies that we have used while purifying these challenging molecules.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e3515"},"PeriodicalIF":2.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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