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Splice, exchange, extend: precision editing of native proteins in live cells. 剪接、交换、扩展：活细胞中天然蛋白的精确编辑。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-08-02 DOI: 10.1016/j.tibtech.2025.07.021
Kevin Schiefelbein, Yael David
{"title":"Splice, exchange, extend: precision editing of native proteins in live cells.","authors":"Kevin Schiefelbein, Yael David","doi":"10.1016/j.tibtech.2025.07.021","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.021","url":null,"abstract":"<p><p>Beyer et al. and Hua et al. developed platforms for precise chemical editing of proteins in living mammalian cells. These approaches enabled site-specific tagging at diverse protein sites without disrupting function. Demonstrated on several key proteins, this technology opens new possibilities for studying protein dynamics and functions in live cells.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776267","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 six-tiered framework for evaluating AI models from repeatability to replaceability. 从可重复性到可替代性评估人工智能模型的六层框架。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-31 DOI: 10.1016/j.tibtech.2025.07.015
Siqi Tian, Alicia Wan Yu Lam, Joseph Jao-Yiu Sung, Wilson Wen Bin Goh
{"title":"A six-tiered framework for evaluating AI models from repeatability to replaceability.","authors":"Siqi Tian, Alicia Wan Yu Lam, Joseph Jao-Yiu Sung, Wilson Wen Bin Goh","doi":"10.1016/j.tibtech.2025.07.015","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.015","url":null,"abstract":"<p><p>Artificial intelligence (AI) is rapidly transforming biotechnology and medicine. But evaluating its safety, effectiveness, and generalizability is increasingly challenging, especially for complex generative models. Traditional evaluation metrics often fall short in high-stakes applications where reliability and adaptability are critical. We propose a six-tiered framework to guide AI evaluation across the dimensions of repeatability, reproducibility, robustness, rigidity, reusability, and replaceability. These tiers reflect increasing expectations, from basic consistency to deployment. Each is defined clearly, with actionable testing methodologies informed by literature. Designed for flexibility, the framework applies to both traditional and generative AI. Through case studies in diagnostics and medical large language models (LLM), we demonstrate its utility in fostering trustworthy, accountable, and effective AI for biomedicine, biotechnology, and beyond.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765533","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
Gas plasma technology mediates deep tissue and anticancer events independently of hydrogen peroxide. 气体等离子体技术介导深层组织和抗癌事件独立于过氧化氢。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-31 DOI: 10.1016/j.tibtech.2025.07.004
Lea Miebach, Marten Hagge, Alice Martinet, Debora Singer, Nadine Gelbrich, Stephan Kersting, Sander Bekeschus
{"title":"Gas plasma technology mediates deep tissue and anticancer events independently of hydrogen peroxide.","authors":"Lea Miebach, Marten Hagge, Alice Martinet, Debora Singer, Nadine Gelbrich, Stephan Kersting, Sander Bekeschus","doi":"10.1016/j.tibtech.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.004","url":null,"abstract":"<p><p>Reactive oxygen species (ROS) can be used as anticancer agents. Some technologies, such as medical gas plasmas, generate large amounts and varieties of these mainly short-lived, reactive molecules. However, it is unclear how far reactive species travel in tissues and which types have major or minor roles in exerting effects. Here, we used novel hydrogel model systems, tumor organoids, and murine and human tissue to help unravel the intricate interplay between gas plasma-derived reactive species and target tissue. For the first time, we identified lateral reactive species diffusion and tumor cell killing for the kINPen plasma jet. Intriguingly, catalase did not rescue in ovo organoid cancers from lethal oxidative damage. This attributes short-lived reactive species or other gas plasma components, but not hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), significant roles in the mediated effects of exposed tissues. Collectively, the findings enable mechanistic insights and empower gas plasma optimization for anticancer treatments.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765535","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
pH-modulated soluble expression of alcohol dehydrogenases in Escherichia coli using adaptive laboratory evolution. ph调节乙醇脱氢酶在大肠杆菌中的可溶性表达的适应性实验室进化。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-31 DOI: 10.1016/j.tibtech.2025.07.013
Suraj Mital, Graham Christie, Annette Alcasabas, Ryan Mellor, Duygu Dikicioglu
{"title":"pH-modulated soluble expression of alcohol dehydrogenases in Escherichia coli using adaptive laboratory evolution.","authors":"Suraj Mital, Graham Christie, Annette Alcasabas, Ryan Mellor, Duygu Dikicioglu","doi":"10.1016/j.tibtech.2025.07.013","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.013","url":null,"abstract":"<p><p>Industrial production of alcohol dehydrogenases (ADHs) is severely hampered by their propensity to form insoluble inclusion bodies during recombinant expression. This work achieves soluble expression of such historically aggregate-prone enzymes in Escherichia coli by addressing the fundamental physicochemical incompatibilities between recombinant proteins and their host environment. Elevating the expression medium to pH 9 and engineering E. coli to adapt to high- pH improved catalytically active soluble yields for industrially significant Rhodococcus ADH-A and ADH-G by 18.55-fold and 26.59-fold, respectively. The evolved E. coli overcame alkaline stress by optimizing energy-intensive metabolic pathways for cytoplasmic pH homeostasis rather than by modulating ribosomal machinery and translation. Seven key mutations acquired during adaptive evolution conferred strategic modifications to cell envelope stress responses, metabolism, and genomic regulation, collectively enhancing fitness. This robust framework proposed for matching the biochemical requirements of heterologous enzymes with host physiology offers a powerful solution for the high-yield production of challenging industrial biocatalysts.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765536","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
Extracellular vesicle manufacture via FACTORY: fully automated collection technology and optimum machinery for clinical translational applications. 通过FACTORY制造细胞外囊泡：全自动收集技术和临床转化应用的最佳机器。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-31 DOI: 10.1016/j.tibtech.2025.06.020
Xing-Chi Liu, Jia-Wen Tian, Jing-Yi Xu, Li-Guo Chen, Zi-Wu Ye, Jue Huang, Lian-Zhi Wu, Zhi-Ling Zhang, Zi-Li Yu, Gang Chen
{"title":"Extracellular vesicle manufacture via FACTORY: fully automated collection technology and optimum machinery for clinical translational applications.","authors":"Xing-Chi Liu, Jia-Wen Tian, Jing-Yi Xu, Li-Guo Chen, Zi-Wu Ye, Jue Huang, Lian-Zhi Wu, Zhi-Ling Zhang, Zi-Li Yu, Gang Chen","doi":"10.1016/j.tibtech.2025.06.020","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.06.020","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) hold significant potential as therapeutic agents and drug carriers. However, current isolation techniques severely limit their clinical application, due to heavy reliance on manual operation, making large-scale isolation of EVs impractical and failing to meet the requirements for clinical translation. Here, we set up the fully automated collection technology and optimum machinery (FACTORY) platform, allowing the efficient collection of high-quality EVs. The platform integrates continuous flow centrifugation and tangential flow filtration (TFF) technologies, achieving a seamless process for the removal of impurities and collection of EVs, thereby ensuring that large scale-manufactured EVs are sterile, mycoplasma free, and low in endotoxins, and exhibit good consistency. We successfully obtained a substantial quantity of EVs utilizing FACTORY, and systematically characterized their EV-specific markers, biological functions, and therapeutic effects. Results indicated that FACTORY significantly promotes the clinical translation of EVs, thereby laying a solid foundation for their application in drug delivery and beyond.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765534","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
AI sheds new light on genome editing. 人工智能为基因组编辑提供了新的视角。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-30 DOI: 10.1016/j.tibtech.2025.07.011
Zhaohui Qin, Zhaolong Deng, Chengwei Li, Daowen Wang, Xiang Ji, Zhen Chen
{"title":"AI sheds new light on genome editing.","authors":"Zhaohui Qin, Zhaolong Deng, Chengwei Li, Daowen Wang, Xiang Ji, Zhen Chen","doi":"10.1016/j.tibtech.2025.07.011","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.011","url":null,"abstract":"<p><p>Artificial intelligence (AI) has revolutionized life sciences, driving transformative advances in engineering clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)-based genome editors for therapeutic and agricultural applications. Recent breakthroughs demonstrate how deep learning accelerates the discovery, engineering, and design of next-generation genome editing tools. In this review, we explore how AI-driven approaches are supercharging genome editing in three aspects: (i) structure-based methods for discovering novel genome editors neglected by conventional methods, (ii) engineering genome editors with enhanced properties, and (iii) the de novo design of entirely new genome editors endowed with bespoke functions. Finally, we discuss the current challenges and envision the future potential of data-driven AI to unlock new possibilities in genome editing, catalyzing innovations across biology and biotechnology.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761458","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
Functional substrate-enhanced bioprinting technology for next-generation organ-on-a-chip: from fabrication to functionalization. 下一代芯片器官的功能基板增强生物打印技术：从制造到功能化。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-29 DOI: 10.1016/j.tibtech.2025.07.014
Gihyun Lee, Soo Jee Kim, Je-Kyun Park
{"title":"Functional substrate-enhanced bioprinting technology for next-generation organ-on-a-chip: from fabrication to functionalization.","authors":"Gihyun Lee, Soo Jee Kim, Je-Kyun Park","doi":"10.1016/j.tibtech.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.014","url":null,"abstract":"<p><p>The integration of bioprinting with advanced substrate technologies offers a transformative approach to tissue engineering, providing vital insight into the development of complex organ-on-a-chip systems. Bioprinting enables the creation of sophisticated microscale biological structures, with the receiving substrate playing a critical role beyond merely supporting the printed constructs. This review explores how substrates enhance both the fabrication precision and functionality of bioprinted tissues, thereby increasing their physiological relevance and analytical capabilities. We demonstrate the potential of substrate-enhanced bioprinting in constructing advanced in vitro models by examining its recent advances, from fabrication technologies to functional applications. This technology has the potential to bridge the gap between traditional cell culture and physiologically relevant tissue models, advancing the development of next-generation organ-on-a-chip platforms.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754401","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
Electrifying food fermentations to promote sustainability. 电气化食品发酵，促进可持续性。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-29 DOI: 10.1016/j.tibtech.2025.07.001
Rui Li, Liuyan Gu, Lars M Blank, Christian Solem, Bin Lai
{"title":"Electrifying food fermentations to promote sustainability.","authors":"Rui Li, Liuyan Gu, Lars M Blank, Christian Solem, Bin Lai","doi":"10.1016/j.tibtech.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.001","url":null,"abstract":"<p><p>The important food microorganism Lactococcus lactis is limited by its fermentative metabolism and low energy yield. This limitation can be partially overcome by activating aerobic respiration which, in a food context, can be difficult to achieve as heme and oxygen must be supplied. Supplying oxygen is particularly challenging due to oxygen mass transfer limitations in food matrices. To address these challenges, we propose to use electro-fermentation to grow L. lactis anaerobically. We propose a technical concept that could potentially increase the biomass productivity by >60% and decrease cooling cost by >90%, and we discuss how this new approach can reshape and enhance the sustainability of the food industry.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754400","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
Third-generation novel technologies for gene editing. 第三代基因编辑新技术。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-29 DOI: 10.1016/j.tibtech.2025.07.012
Pushpendra K Gupta, Sourabh Kumar
{"title":"Third-generation novel technologies for gene editing.","authors":"Pushpendra K Gupta, Sourabh Kumar","doi":"10.1016/j.tibtech.2025.07.012","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.07.012","url":null,"abstract":"<p><p>Gene editing technologies have revolutionized the field of biotechnology. CRISPR-Cas methods using RNA-guided enzymes are the most used gene editing tools and have produced gene-edited crops (rice, wheat, corn, etc.) and human therapeutics (Casgevy, approved for commercial use; Vertex Pharmaceuticals). However, these systems have some limitations, including the requirement of a protospacer adjacent motif sequence, generation of undesirable double-strand breaks (DSBs), and the inability to edit long genomic segments. Some of these limitations were partially addressed by the development of second-generation editors, including base editors (BEs) and prime editors (PEs). Third-generation gene editing technologies such as seekRNA and bridgeRNA can overcome most of these limitations and are the subject of this review.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754402","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-a-chip systems for modeling tumor and normal tissue microenvironments in radiotherapy research. 用于肿瘤和放射治疗研究中正常组织微环境建模的器官芯片系统。
IF 14.9 1区 工程技术
Trends in biotechnology Pub Date : 2025-07-24 DOI: 10.1016/j.tibtech.2025.07.002
Rohollah Nasiri, Arnav Sankaranthi, Guillem Pratx
{"title":"Organ-on-a-chip systems for modeling tumor and normal tissue microenvironments in radiotherapy research.","authors":"Rohollah Nasiri, Arnav Sankaranthi, Guillem Pratx","doi":"10.1016/j.tibtech.2025.07.002","DOIUrl":"10.1016/j.tibtech.2025.07.002","url":null,"abstract":"<p><p>Radiation therapy (RT) precisely targets tumors with ionizing radiation, aiming to achieve local control while minimizing collateral damage to surrounding healthy tissues. Radiation research is often carried out in animal models, but these suffer from ethical issues, high cost of operation, low throughput, and low correlation to responses in humans. The advent of microfluidic organ-on-a-chip (OoC) technology offers a promising alternative to precisely and reproducibly model the physiology of different tissues in a laboratory setting. Furthermore, organ-on-a-chip models can be constructed from patient-specific tissues to tailor therapies while enabling fine control over relevant microenvironmental factors. In this review, we highlight emerging research at the intersection of radiation biology and microphysiological models, with a focus on the unique capabilities enabled by these advanced technologies.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12313272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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