Biotechnology Progress最新文献

筛选
英文 中文
On-deck pH measurement with integrated feedback control on a micro-scale platform for monoclonal antibody low pH viral inactivation. 微尺度单克隆抗体低pH病毒灭活平台上集成反馈控制的甲板pH测量。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-05-05 DOI: 10.1002/btpr.88516
Paras Sharma, Nikolas von den Eichen, Sabine Schweisgut, Lars Robbel, Michael Schmitt, Daniel G Bracewell
{"title":"On-deck pH measurement with integrated feedback control on a micro-scale platform for monoclonal antibody low pH viral inactivation.","authors":"Paras Sharma, Nikolas von den Eichen, Sabine Schweisgut, Lars Robbel, Michael Schmitt, Daniel G Bracewell","doi":"10.1002/btpr.88516","DOIUrl":"https://doi.org/10.1002/btpr.88516","url":null,"abstract":"<p><p>The increasing demand for efficient monoclonal antibody manufacturing has accelerated the adoption of high throughput process development (HTPD) platforms, which enable rapid, automated screening of downstream operations. However, the integration of non-chromatographic steps such as low pH viral inactivation (VI) within automated workflows remains limited, largely due to the absence of a micro-scale method for accurate, on-deck pH measurement and control. This study presents the development and implementation of an automated pH measurement and feedback control system using optical pH sensors immobilized within 96-well microplates. The approach enables non-invasive, real-time monitoring of pH across the acidic range required for VI and is fully compatible with standard liquid-handling platforms. Integration of a feedback control algorithm allowed autonomous acid and base addition to achieve precise target pH values during both acidification and neutralization phases. The method achieved strong agreement between measured and expected pH values following optimization of measurement conditions, including ionic strength adjustment. The system was further integrated with Sartobind® Q and cation exchange chromatography steps to demonstrate an end-to-end automated workflow. Systematic assessment of cation exchange chromatography performance under controlled loading conditions enabled direct visualization of separation behavior and early identification of sub-optimal operating regions, demonstrating the platform's capability to expand experimental space and accelerate mechanistic process understanding. This work establishes a micro-scale, fully automated downstream platform with pH control, bridging a critical technological gap and advancing the vision of an end-to-end HTPD system for biopharmaceutical purification.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88516"},"PeriodicalIF":2.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833040","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
A PVA/chitosan/gelatin scaffold incorporating salicylic acid-loaded TiO₂ nanoparticles enhances collagen I expression and accelerates cutaneous wound repair in mice. PVA/壳聚糖/明胶支架结合负载水杨酸的tio2纳米颗粒增强胶原I表达,加速小鼠皮肤伤口修复。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-05-05 DOI: 10.1002/btpr.88500
Parvin Safaiefar, Somayeh Reiisi, Mehdi Haghi, Sadegh Shirian
{"title":"A PVA/chitosan/gelatin scaffold incorporating salicylic acid-loaded TiO₂ nanoparticles enhances collagen I expression and accelerates cutaneous wound repair in mice.","authors":"Parvin Safaiefar, Somayeh Reiisi, Mehdi Haghi, Sadegh Shirian","doi":"10.1002/btpr.88500","DOIUrl":"https://doi.org/10.1002/btpr.88500","url":null,"abstract":"<p><p>Wound healing is a complex biological process requiring coordinated cellular and molecular responses, motivating the development of bioactive scaffolds capable of modulating the wound microenvironment. In this study, a nanocomposite scaffold composed of chitosan, polyvinyl alcohol (PVA), and gelatin incorporating salicylic acid-loaded titanium dioxide nanoparticles (TiO₂ NPs) was fabricated and evaluated for wound-healing applications. TiO₂ nanoparticles synthesized via a co-precipitation method exhibited nanoscale dimensions, high crystallinity, a negative surface charge (-19.4 mV), and a drug-loading efficiency exceeding 90%. The scaffold showed good structural integrity under physiological conditions, excellent hemocompatibility (<5% hemolysis), and a swelling ratio of approximately 50%. Sustained, pH-independent release of salicylic acid was observed. In vitro studies demonstrated that the nanocomposite increased fibroblast migration by approximately 90% compared with untreated controls and significantly upregulated COL1 gene expression by 2.5-fold (p < 0.05), while maintaining high cell viability. In a murine excisional wound model, the nanocomposite-treated group achieved 85% wound closure by day 10, compared with 30% in untreated wounds and 50% in the drug-free scaffold group (p < 0.05), along with improved epidermal regeneration. Overall, these results indicate that controlled delivery of salicylic acid from a TiO₂-containing polymeric scaffold supports fibroblast activity, collagen-related responses, and wound closure, providing a rational basis for further optimization of multifunctional wound dressings.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88500"},"PeriodicalIF":2.5,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832996","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
Data-driven design of deterministic lateral displacement microfluidic devices for CTC separation. 确定性横向位移微流控分离装置的数据驱动设计。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-29 DOI: 10.1002/btpr.88515
Tanbir Sarowar, Sadia Anjum Mim, Xiaolin Chen
{"title":"Data-driven design of deterministic lateral displacement microfluidic devices for CTC separation.","authors":"Tanbir Sarowar, Sadia Anjum Mim, Xiaolin Chen","doi":"10.1002/btpr.88515","DOIUrl":"https://doi.org/10.1002/btpr.88515","url":null,"abstract":"<p><p>Circulating tumor cells (CTCs) are established biomarkers for cancer diagnosis and therapeutic monitoring, yet their extreme rarity in peripheral blood and size overlaps with leukocytes present substantial technical barriers to clinical deployment. Deterministic lateral displacement (DLD) is a promising microfluidic technique for label-free, continuous CTC separation. However, due to the extreme heterogeneity of cancer cells, rational device design requires computationally expensive iterative simulation across multi-dimensional geometric parameter spaces. Here we present a data-driven design framework that integrates validated computational fluid dynamics (CFD) simulations with supervised machine learning to enable rapid prediction of particle separation behavior and critical diameter in DLD arrays. A dataset of approximately 8.5 million trajectory data points was generated across 1160 unique combinations of array period number (N = 3-48) and particle diameter (1-20 μm) using COMSOL-based CFD. Four regression algorithms, Gradient Boosting, Random Forest, k-Nearest Neighbors, and Multi-Layer Perceptron, were trained and evaluated on trajectory prediction and critical diameter estimation. Random Forest achieved the highest accuracy, with a test-set R<sup>2</sup> of 0.994 and a mean absolute error of 0.31 μm in critical diameter prediction. A clinical case study targeting colorectal CTC separation from blood demonstrated that the ML-guided design workflow converged on an optimal device configuration (N = 15, D<sub>c</sub> = 10-12 μm) in under 2.3 s, representing a speedup exceeding four orders of magnitude compared to equivalent CFD iteration. The framework enables direct translation of CTC size distributions into DLD device configurations and provides a scalable foundation for reproducible microfluidic process development in biomedical applications.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88515"},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760831","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
Protein hydrolysates in cell culture: Toward multi-omics characterization. 细胞培养中的蛋白水解物:迈向多组学表征。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-28 DOI: 10.1002/btpr.88505
Michelle Combe, Brandon M Wrage, Angel Varela-Rohena, Stanislav Sokolenko
{"title":"Protein hydrolysates in cell culture: Toward multi-omics characterization.","authors":"Michelle Combe, Brandon M Wrage, Angel Varela-Rohena, Stanislav Sokolenko","doi":"10.1002/btpr.88505","DOIUrl":"https://doi.org/10.1002/btpr.88505","url":null,"abstract":"<p><p>The high cost of conventional cell culture media has driven demand for sustainable, cost-effective serum-free formulations in biopharmaceutical manufacturing and cultivated meat production. Although plant- and yeast-derived hydrolysates are generally considered to be promising additives, significant variability in raw materials and processing conditions results in substantial compositional and batch-to-batch differences between products, making it challenging to predict effectiveness in cell culture a priori. This review examines hydrolysate media additives through the specific lens of comprehensive multi-omic characterization as a means of addressing this uncertainty. While typical characterization is often limited to metrics such as degree of hydrolysis or color, detailed metabolomic and peptidomic profiling remains uncommon. We identify a gap in systematic, high-resolution characterization and argue that integrating compositional and bioactivity analyses is essential to transition hydrolysates from undefined inputs toward semi-defined media components.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88505"},"PeriodicalIF":2.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760788","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
Addressing challenging impurities in fusion proteins: A comprehensive review and cost-effective strategy for HCP and low molecular weight species control. 解决融合蛋白中具有挑战性的杂质:HCP和低分子量物种控制的综合综述和成本效益策略。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-23 DOI: 10.1002/btpr.88512
Anindita Das, Madhava Ram Paranandi, Karthikeyan Subbiramani, Ranganadha Reddy
{"title":"Addressing challenging impurities in fusion proteins: A comprehensive review and cost-effective strategy for HCP and low molecular weight species control.","authors":"Anindita Das, Madhava Ram Paranandi, Karthikeyan Subbiramani, Ranganadha Reddy","doi":"10.1002/btpr.88512","DOIUrl":"https://doi.org/10.1002/btpr.88512","url":null,"abstract":"<p><p>Fusion proteins represent a rapidly expanding class of biotherapeutics engineered by combining functional domains from different proteins to enhance therapeutic efficacy, stability, and pharmacokinetics. Their unique design enables extended half-life, reduced dosing frequency, and multi-targeting capabilities, making them highly versatile for diverse therapeutic indications. However, the manufacturing of fusion proteins presents significant challenges, particularly in managing complex product- and process-related impurities such as host cell proteins (HCPs), fragments, and low-molecular-weight (LMW) species. These impurities are difficult to eliminate due to their structural and physicochemical similarity to the target protein, complicating purification and scale-up. Part I of this paper provides a comprehensive review of published studies addressing impurity characterization and control strategies in fusion protein manufacturing. The review highlights critical impurity types, analytical tools for detection and quantification, and process strategies for effective removal while maintaining product integrity and regulatory compliance. Part II presents a case study from Kemwell Biopharma, illustrating a cost-effective platform purification strategy for complex fusion proteins. The approach is applicable to non-tagged, Fc-based, and multispecific fusion protein formats and demonstrates efficient removal of HCPs and LMW impurities while achieving high yield and purity. Together, the review and case study provide both a broad scientific understanding and a practical demonstration of scalable impurity control approaches, offering valuable insights for the development of robust and economically viable manufacturing processes for next-generation fusion protein therapeutics.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88512"},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760810","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
Strategies for removing two "problematic" host cell proteins, using an "end-to-end" approach. 使用“端到端”方法去除两种“有问题”的宿主细胞蛋白的策略。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-23 DOI: 10.1002/btpr.88514
Greg Evangelist, Chris Kwiatkowski, Krishnakumar Malu, Suli Lu, Linda Yi, Sarwat Khattak, Brad Stanley
{"title":"Strategies for removing two \"problematic\" host cell proteins, using an \"end-to-end\" approach.","authors":"Greg Evangelist, Chris Kwiatkowski, Krishnakumar Malu, Suli Lu, Linda Yi, Sarwat Khattak, Brad Stanley","doi":"10.1002/btpr.88514","DOIUrl":"https://doi.org/10.1002/btpr.88514","url":null,"abstract":"<p><p>Host cell proteins (HCPs) are critical process-related impurities of recombinant protein biopharmaceuticals that have the potential to impact product safety and efficacy. In this study, two residual HCPs, heat shock protein 90 beta and perilipin-4-like, produced from a CHO cell line, were identified during the development of a late-stage platform Immunoglobulin G subclass 1 (IgG1) monoclonal antibody process. A risk assessment was performed that included identification of HCPs, homology with their human protein counterparts, and prior non-clinical and clinical experience. The outcome deemed these two species as \"problematic\" and target levels were established to guide approaches for removal. Given the high productivity of the upstream and downstream platform processes, the goal was to explore conditions that minimize deviations from the platform. An end-to-end approach was performed that evaluated downstream levers, including Protein A washes, polishing chromatography operational parameters, and exploration of depth filter media. Upstream levers were also explored, evaluating effects of temperature shift and modulation of iron and citrate to help control levels of both HCP species. The results presented in this study demonstrated the upstream and downstream conditions achieved effective removal of the two HCP species to meet drug substance targets.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88514"},"PeriodicalIF":2.5,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760794","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
Evaluating the impact of ionic strength on retention of minute virus of mice during small virus-retentive filtration. 小病毒保留过滤过程中离子强度对小鼠微小病毒保留的影响。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-20 DOI: 10.1002/btpr.88511
Cody Murphy, Ashley Slocum, Matthew Tierson, Benjamin Cacace, Paul Genest, Kathryn Martin Remington, Justin Hale
{"title":"Evaluating the impact of ionic strength on retention of minute virus of mice during small virus-retentive filtration.","authors":"Cody Murphy, Ashley Slocum, Matthew Tierson, Benjamin Cacace, Paul Genest, Kathryn Martin Remington, Justin Hale","doi":"10.1002/btpr.88511","DOIUrl":"https://doi.org/10.1002/btpr.88511","url":null,"abstract":"<p><p>Small virus-retentive filtration (VRF) is a critical unit operation utilized in the viral clearance package to ensure the viral safety of biotherapeutics. This step is relied upon to provide effective parvovirus retention of ≥4 log reduction value (LRV) (e.g., minute virus of mice; MVM), and robust retention of larger viruses. Biomolecules, including multispecific antibodies and recombinant proteins, present purification challenges that require multiple chromatography columns to achieve final purity specifications. These additional polishing steps may utilize high ionic strength solution conditions to meet purity targets, and it is critical to assess if those process conditions impact the viral retention performance of the subsequent VRF operations. In one instance, retention performance was lower than expected (≤4 LRV) and was attributed to the use of a high ionic strength buffer. Two possible mechanisms were investigated, that is, reduction in the effective size of the MVM virus (~25 nm) and/or an increase in the membrane filter pore size, as observed with increase in the virus filter permeability. Based on modeling and experimental data presented here, at high ionic strength solution conditions the hydrodynamic size of MVM is reduced while virus-retentive membrane effective pore size is larger, as compared to low ionic strength conditions. Additionally, MVM LRV and membrane permeability of multiple commercial-grade virus filters were impacted by high ionic strength and process interruptions. These results demonstrate that high ionic strength solution conditions could impact parvovirus retention performance, and these findings may guide process development for biotherapeutics operating under similar atypical solution conditions.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88511"},"PeriodicalIF":2.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728196","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
Effect of cell retention techniques in Komagataella phaffii lab-scale continuous processes 细胞保留技术对法菲小松草实验室规模连续工艺的影响。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-07 Epub Date: 2025-11-18 DOI: 10.1002/btpr.70092
Marina Y. Linova, Satish K. Kodiripaka, Edite Martins, Sobhana A. Sripada, Stefano Menegatti, John M. Woodley
{"title":"Effect of cell retention techniques in Komagataella phaffii lab-scale continuous processes","authors":"Marina Y. Linova,&nbsp;Satish K. Kodiripaka,&nbsp;Edite Martins,&nbsp;Sobhana A. Sripada,&nbsp;Stefano Menegatti,&nbsp;John M. Woodley","doi":"10.1002/btpr.70092","DOIUrl":"10.1002/btpr.70092","url":null,"abstract":"<p>Perfusion technologies play a growing role in the implementation of continuous processes for biotherapeutics production in mammalian-based manufacturing. However, their application to alternative production hosts is limited. Cell retention systems are of key importance for the efficiency of perfusion bioreactors. In this study, we investigate two cell retention technologies for the development of lab-scale <i>Komagataella phaffii</i> continuous processes. An acoustic-based process (AP) and a membrane-based process (MP) were developed using an acoustic cell separator (ACS) and a vibrating membrane filtration (VMF) device, respectively. Both systems allowed for continuous cell recycle and production of scFv13R4 antibody fragment for 8 days (AP) and 9 days (MP), without loss in productivity, while maintaining high viability (greater than 90%). Higher volumetric and specific productivities were achieved during the AP process, namely 50.63 ± 1.63 mg L<sup>−1</sup> day<sup>−1</sup> and 1.09 ± 0.07 mg g<sup>−1</sup> day<sup>−1</sup>, against the 32.29 ± 1.21 mg L<sup>−1</sup> day<sup>−1</sup> and 0.44 ± 0.02 mg g<sup>−1</sup> day<sup>−1</sup> afforded by the MP process. The VMF device provided 100% separation efficiency with biomass accumulating up to concentrations of 74.1 ± 0.1 g L<sup>−1</sup> dry cell weight (DCW), whereas the acoustic device reached 55.1 ± 0.47 g L<sup>−1</sup> DCW at 98% separation efficiency. The acoustic device showed selectivity towards larger and more complex cells in the yeast population, which might be linked to the observed higher productivities for the AP process. This study discusses the advantages and drawbacks of both cell retention technologies and provides an outlook towards their future investigation in <i>K. phaffii</i> perfusion processes.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling microbial and microalgal chassis for therapeutic and diagnostic protein expression 揭示微生物和微藻底盘治疗和诊断蛋白表达。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-07 Epub Date: 2026-01-21 DOI: 10.1002/btpr.70098
Lakshika Bhandari, Samir Kulkarni, Gunjan Prakash
{"title":"Unveiling microbial and microalgal chassis for therapeutic and diagnostic protein expression","authors":"Lakshika Bhandari,&nbsp;Samir Kulkarni,&nbsp;Gunjan Prakash","doi":"10.1002/btpr.70098","DOIUrl":"10.1002/btpr.70098","url":null,"abstract":"<p>Biopharmaceuticals are becoming one of the most successful clinical therapeutic products for treating various disorders and are gradually being utilized across nearly all areas of medicine. They have revolutionized the treatment of numerous diseases and continue to represent a significant area of research and development. Presently, host cell systems like bacteria, yeast, insects, and mammalian cells dominate the production of both therapeutic and diagnostic proteins. This review explores the strengths and limitations of these existing host systems for recombinant protein production, emphasizing the promising potential of microalgal systems for expressing therapeutic and diagnostic proteins. It accentuates the advantages of microalgae, such as their rapid growth rates, scalability, and sustainability. We delve into the intricacies of glycosylation patterns in microalgae, comparing them with those in other expression systems. This review highlights recent advancements in algal-based protein expression systems for diagnostic and therapeutic applications. It also outlines a strategic roadmap for future developments in biopharmaceutical production, emphasizing how each expression system's unique characteristics can help meet modern medicine's growing demands.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008787","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
Augmenting therapeutic protein production in CHO cells: A proline-based selection strategy for enhanced productivity and product quality 在CHO细胞中增加治疗性蛋白质的生产:基于脯氨酸的选择策略,以提高生产力和产品质量。
IF 2.5 3区 生物学
Biotechnology Progress Pub Date : 2026-04-07 Epub Date: 2025-11-17 DOI: 10.1002/btpr.70091
Bin Zhao, Boya Zhang, Yanshen Kang, Shenghai Liu, Zhangying Jia, Chenlin Lu, Yajing Cao, April Xu, Kyu-Sung Lee, Zheng Zhang, Jing Song
{"title":"Augmenting therapeutic protein production in CHO cells: A proline-based selection strategy for enhanced productivity and product quality","authors":"Bin Zhao,&nbsp;Boya Zhang,&nbsp;Yanshen Kang,&nbsp;Shenghai Liu,&nbsp;Zhangying Jia,&nbsp;Chenlin Lu,&nbsp;Yajing Cao,&nbsp;April Xu,&nbsp;Kyu-Sung Lee,&nbsp;Zheng Zhang,&nbsp;Jing Song","doi":"10.1002/btpr.70091","DOIUrl":"10.1002/btpr.70091","url":null,"abstract":"<p>Chinese hamster ovary (CHO) cells have emerged as the predominant mammalian host for the production of therapeutic recombinant proteins, including monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and fusion proteins. To meet the growing demand for biologics and reduce manufacturing costs, the exploitation of efficient cell line development platforms is essential. Over the past decades, various selection markers, such as dihydrofolate reductase (DHFR), glutamine synthetase (GS), and antibiotic resistance genes, have been widely utilized in the development of production cell lines. In this study, we introduce the proline selection system, an alternative metabolic selection strategy, as an efficient approach to optimize our CHO cell line development platform. By employing yeast <i>PRO1</i> and <i>PRO2</i> genes as selection markers, proline selection effectively complements GS selection to establish high-producing cell lines for both mAbs and bsAbs. In particular, the integration of <i>PRO1</i> and <i>PRO2</i> genes into a single plasmid, in conjunction with the GS gene, significantly enhances productivity for asymmetric molecules. Optimized chain configuration across proline and GS selection plasmids can further boost protein yield. Additionally, the overexpression of regulator proteins can be leveraged with proline selection to enhance antibody production or fine-tune product quality. Taken together, the incorporation of proline selection into CHO cell line development, particularly when combined with GS selection, provides a consistent and streamlined strategy to meet the growing demand for high-quality biologics in the pharmaceutical industry.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538977","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信
小红书