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Organoid bioprinting for vascularized tumor assembloids. 血管化肿瘤组合的类器官生物打印。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-07 DOI: 10.1016/j.tibtech.2026.04.009
Zhenzhen Zhou, Yuan Pang, Zhendong Liao, Chang Zhou, Meiling Fu, Changru Liu, Yuting Guo, Kamto Yang, Jianyu He, Botao Gao, Marie Shinohara, Yasuyuki Sakai, Wei Sun
{"title":"Organoid bioprinting for vascularized tumor assembloids.","authors":"Zhenzhen Zhou, Yuan Pang, Zhendong Liao, Chang Zhou, Meiling Fu, Changru Liu, Yuting Guo, Kamto Yang, Jianyu He, Botao Gao, Marie Shinohara, Yasuyuki Sakai, Wei Sun","doi":"10.1016/j.tibtech.2026.04.009","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.009","url":null,"abstract":"<p><p>The complexity and heterogeneity of the tumor microenvironment significantly influence cancer progression and therapeutic outcomes, highlighting the need for physiologically relevant in vitro models. In this study, we present vascularized tumor assembloids (VTASs) constructed via organoid bioprinting using a cell aggregate-rich living gel composed of endothelialized hepatic tumor aggregates and suspended endothelial cells. These VTASs recapitulate dense, volumetric, and hierarchical tissue architectures with functional vasculature and hepatic characteristics. Drug screening revealed reduced apoptosis and delayed intracellular drug accumulation in VTASs with dense microvasculature compared with cell-based or sparsely vascularized models, demonstrating differential responses to cisplatin, sorafenib, combination therapy, and doxorubicin. Co-culture with immune cells captured monocyte-endothelial interactions under inflammatory stimulation. Upon in vivo implantation, VTASs formed perfused tumorlike structures that recapitulated key histological and functional features of human cancer. Thus, VTASs provide a scalable and physiologically relevant platform for studying tumor biology, immune interactions, and high-throughput anticancer drug evaluation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patentability of antibodies in the artificial intelligence era. 人工智能时代抗体的可专利性。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-06 DOI: 10.1016/j.tibtech.2026.04.014
Yu Yao, Fei Yang
{"title":"Patentability of antibodies in the artificial intelligence era.","authors":"Yu Yao, Fei Yang","doi":"10.1016/j.tibtech.2026.04.014","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.014","url":null,"abstract":"<p><p>Artificial intelligence can accelerate antibody discovery, potentially reshaping how inventions must be disclosed while raising standards for truly creative breakthroughs. This science and society article advocates modernizing 'undue experimentation' criteria, giving appropriate evidentiary weight to in silico data, and redefining a skilled person's capabilities, thereby rewarding genuine human inventions while preserving patent incentives.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR-based technologies for large DNA insertions. 基于crispr的大型DNA插入技术。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-06 DOI: 10.1016/j.tibtech.2026.04.004
Mary Gracen A Fuller, Matthew Foley, Rodolphe Barrangou
{"title":"CRISPR-based technologies for large DNA insertions.","authors":"Mary Gracen A Fuller, Matthew Foley, Rodolphe Barrangou","doi":"10.1016/j.tibtech.2026.04.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.004","url":null,"abstract":"<p><p>While the advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based technologies has democratized the genesis of precise mutations, there is a need for more sophisticated tools to enable large-scale DNA manipulations, advancing genome editing across medicine, biotechnology, and agriculture. The success of Cas9 and Cas12 has hinged on the generation of precise DNA nicks and double-stranded breaks (DSBs), enabling local sequence mutagenesis, albeit of a limited size range. Emerging effectors combining Cas with other enzymatic functions, such as CRISPR-associated transposons and site-specific recombinases, enable larger integrations. Sophisticated combinations such as programmable addition via site-specific targeting element (PASTE), prime-editing-assisted site-specific integrase gene editing (PASSIGE), and prime-editing-mediated recombination of opportune target (PrimeRoot) expand payload options and DSB-free editing modalities, with translational potential for next-generation crop breeding in sustainable agriculture and the development of gene and cell therapies in personalized medicine.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of anti-drug antibodies during monoclonal antibody drug therapy. 单克隆抗体药物治疗中抗药物抗体的检测。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-05 DOI: 10.1016/j.tibtech.2026.04.003
Frans Kokojka, Denis Mulleman, Robert S Marks
{"title":"Detection of anti-drug antibodies during monoclonal antibody drug therapy.","authors":"Frans Kokojka, Denis Mulleman, Robert S Marks","doi":"10.1016/j.tibtech.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.003","url":null,"abstract":"<p><p>Therapeutic monoclonal antibodies can elicit anti-drug antibodies (ADAs) in patients, which impact drug pharmacokinetics, reduce efficacy, and occasionally cause hypersensitivity reactions. Growing evidence indicates that early detection of ADA responses improves therapy outcomes, yet their monitoring has remained underappreciated. Conventional assays are complex, time-consuming, and confined to centralized laboratories, thereby delaying clinical decisions. In contrast, emerging biosensor technologies represent a promising alternative for timely, on-site ADA detection. This review examines advancements in ADA detection and provides a critical overview of its clinical relevance based on contemporary findings. Furthermore, the challenges and complexities of accurately biosensing ADAs are discussed. Finally, we explore the prospects of biosensors for on-site analysis and their integration into proactive therapeutic drug monitoring.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated directed evolution and semirational design of Pyrococcus furiosus Argonaute for ultrasensitive tetracycline detection. 用于四环素超灵敏检测的红色焦球菌的定向进化与半种群设计。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-05 DOI: 10.1016/j.tibtech.2026.04.008
Yanyan Chai, Bosheng Zhou, Wanqi Chen, Yuxuan Hu, Bingjie Zheng, Guozhen Liu, Yonggang Hu
{"title":"Integrated directed evolution and semirational design of Pyrococcus furiosus Argonaute for ultrasensitive tetracycline detection.","authors":"Yanyan Chai, Bosheng Zhou, Wanqi Chen, Yuxuan Hu, Bingjie Zheng, Guozhen Liu, Yonggang Hu","doi":"10.1016/j.tibtech.2026.04.008","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.008","url":null,"abstract":"<p><p>In this study, we report an integrated strategy combining directed evolution and semirational design to engineer a high-performance Pyrococcus furiosus Argonaute (PfAgo) variant. The optimized variant exhibited an 8.85-fold increase in catalytic efficiency, substantially enhanced soluble expression, and improved tolerance to elevated salt and metal ion conditions, enabling sensitive nucleic acid detection with a detection limit in the picomolar range. Mechanistic analyses suggested that these improvements may arise from reinforcement of the dimerization interface to stabilize the enzyme's active state, optimization of the catalytic center, and the introduction of charge-shielding salt bridges. Finally, a biosensing platform based on the engineered PfAgo achieved a detection limit of 10 fmol l<sup>-1</sup> for tetracycline, demonstrating its strong potential for sensitive and robust detection. This work provides a generalizable framework for enhancing Argonaute performance and advances their application in field-deployable diagnostics across clinical, environmental, and food safety settings.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A bacterial-derived quorum-sensing platform enables dynamic metabolic control in yeast. 细菌衍生的群体感应平台使酵母的动态代谢控制成为可能。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-05 DOI: 10.1016/j.tibtech.2026.04.007
Haotian Zhai, Xinyue Liu, Pinzeng Guo, Yalin Guo, Xiaoyu Yang, Qingsheng Qi, Jens Nielsen, Zihe Liu, Yun Chen, Jin Hou
{"title":"A bacterial-derived quorum-sensing platform enables dynamic metabolic control in yeast.","authors":"Haotian Zhai, Xinyue Liu, Pinzeng Guo, Yalin Guo, Xiaoyu Yang, Qingsheng Qi, Jens Nielsen, Zihe Liu, Yun Chen, Jin Hou","doi":"10.1016/j.tibtech.2026.04.007","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.007","url":null,"abstract":"<p><p>Dynamic regulation of metabolic pathways is critical for optimizing microbial production, yet robust quorum-sensing (QS) systems remain largely unavailable in eukaryotic microorganisms. Here, we establish a bacterial-derived QS platform in Saccharomyces cerevisiae by repurposing the noncanonical RpaI/RpaR system (a LuxI/R-type QS system), which produces p-coumaroyl-homoserine lactone as a signal molecule, bypassing a fundamental metabolic barrier that has prevented functional bacterial QS in eukaryotes. The engineered circuit features low leakage, high sensitivity, and broad dynamic range. By coupling QS with signal amplification and clustered regularly interspaced short palindromic repeats (CRISPR) interference modules, we create a bifunctional cascade system enabling autonomous transcriptional activation and repression. This QS platform enables growth-production decoupling and improves the production of cordycepin, geraniol, and 3-hydroxypropionic acid in both baseline and high-producing strains. Our work establishes a functional bacterial QS system in yeast and expands the synthetic biology toolkit for eukaryotic hosts.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A DNA-logic artificial cell wall for dimethyl sulfoxide-free cryopreservation and post-thaw proliferation. 无二甲亚砜冷冻保存及解冻后增殖的dna逻辑人工细胞壁。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-04 DOI: 10.1016/j.tibtech.2026.04.010
Heng Gao, Zhongxiang Ding, Leiming Chu, Yanting Zhai, Shixuan Yang, Honglin Liu
{"title":"A DNA-logic artificial cell wall for dimethyl sulfoxide-free cryopreservation and post-thaw proliferation.","authors":"Heng Gao, Zhongxiang Ding, Leiming Chu, Yanting Zhai, Shixuan Yang, Honglin Liu","doi":"10.1016/j.tibtech.2026.04.010","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.04.010","url":null,"abstract":"<p><p>Cell cryopreservation is fundamental to modern biomedicine but is constrained by the cytotoxicity of conventional cryoprotectants like dimethyl sulfoxide and the frequent impairment of cellular function after thawing. Here, we introduce a biocompatible DNA-logic artificial cell wall, engineered by integrating a programmable DNA-logic framework with a calcium alginate hydrogel. This platform simultaneously addresses the two main challenges in cryopreservation: physical damage from ice crystals and poor biological recovery after thawing. The hydrogel physically shields cells from ice injury, while the programmable DNA system enables cell-type-specific recognition, activates intracellular signaling pathways, promotes post-thaw functional recovery, and inhibits ice growth. By merging mechanical protection with biological activation, this dual-mechanism strategy significantly improves cell survival and functional restoration after thawing. This approach resolves the traditional compromise between structural preservation and functional recovery, offering a promising route toward high-fidelity cell preservation and therapy.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Organ-on-chip technologies at the cancer-thrombosis interface. 器官芯片技术在癌症-血栓界面。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-01 Epub Date: 2025-10-25 DOI: 10.1016/j.tibtech.2025.10.001
Inês Soares Marques, Raquel Almeida, Pedro F Costa
{"title":"Organ-on-chip technologies at the cancer-thrombosis interface.","authors":"Inês Soares Marques, Raquel Almeida, Pedro F Costa","doi":"10.1016/j.tibtech.2025.10.001","DOIUrl":"10.1016/j.tibtech.2025.10.001","url":null,"abstract":"<p><p>Cancer-associated thrombosis (CAT) is the second leading cause of death among cancer patients, driven by tumour-haemostasis interactions. While traditional models have proven invaluable to study this process, they often fail to replicate its complexity. Organ-on-chip (OoC) offers a promising alternative, potentially enhancing understanding of CAT mechanisms and advancing therapeutic strategies.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"1193-1197"},"PeriodicalIF":14.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic regulation of oleaginous yeast metabolism for chemical production. 产油酵母化学生产代谢的动态调控。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-01 Epub Date: 2025-11-03 DOI: 10.1016/j.tibtech.2025.10.014
Kaifeng Wang, Mei-Li Sun, Xiao-Jun Ji
{"title":"Dynamic regulation of oleaginous yeast metabolism for chemical production.","authors":"Kaifeng Wang, Mei-Li Sun, Xiao-Jun Ji","doi":"10.1016/j.tibtech.2025.10.014","DOIUrl":"10.1016/j.tibtech.2025.10.014","url":null,"abstract":"<p><p>Dynamic regulation enables precise, signal-responsive control of metabolism in oleaginous yeasts, overcoming limitations of static engineering. By leveraging metabolite and spatiotemporal cues, these systems decouple growth from production and enhance the yield of target chemicals. Integrating such strategies holds promise for building robust and high-performance oleaginous yeast cell factories.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"1198-1202"},"PeriodicalIF":14.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chloroplast engineering for enhancing photosynthetic efficiency and agronomic traits. 提高光合效率和农艺性状的叶绿体工程。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2026-05-01 Epub Date: 2025-10-08 DOI: 10.1016/j.tibtech.2025.09.011
Srishti Jaswal, Ashish K Srivastava, Anand Ballal, Santosh K Sandur
{"title":"Chloroplast engineering for enhancing photosynthetic efficiency and agronomic traits.","authors":"Srishti Jaswal, Ashish K Srivastava, Anand Ballal, Santosh K Sandur","doi":"10.1016/j.tibtech.2025.09.011","DOIUrl":"10.1016/j.tibtech.2025.09.011","url":null,"abstract":"<p><p>Plant chloroplast, the vital organelle that performs photosynthesis, is essential for sustaining life on Earth. It not only converts light energy into food while releasing O<sub>2</sub> in the process, but also consumes CO<sub>2</sub>, thereby reducing the pace of climate warming. Stresses such as heat, oxidative stress, fluctuating light, and herbicides negatively impact the photosynthetic potential of chloroplasts. Hence, concerted research efforts have focused on chloroplast engineering to improve the photosynthetic processes for enhancing plant growth, crop yield, and stress resilience. In this context, this review discusses recent advances in chloroplast engineering, which include manipulation of gene(s) involved in photosynthesis. Additionally, non-genetic approaches that enhance photosynthesis are detailed. Finally, the future directions of research that are likely to yield photosynthetically efficient crops are emphasized.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"1279-1292"},"PeriodicalIF":14.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","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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