{"title":"De-extinction and beyond: trait design powered by generative AI.","authors":"Siqi Wang, Wei Li, Guihai Feng","doi":"10.1016/j.tibtech.2025.09.015","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.015","url":null,"abstract":"<p><p>Functional de-extinction is the process of creating organisms with traits resembling those of extinct species that benefit modern ecosystems. Advances in genome-wide sequencing, gene editing and traditional cloning technologies have substantially accelerated progress toward de-extinction. However, beyond ongoing ethical debates, this field still faces significant technical challenges. In this opinion, we outline current de-extinction strategies and discuss their advantages and limitations. We then propose a forward-looking framework for de novo trait design by integrating generative AI, including genomic language models, together with ex vivo life engineering. This AI-driven approach to de-extinction may offer powerful tools for uncovering developmental regulatory mechanisms and promoting biodiversity conservation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281120","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}
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":"https://doi.org/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":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-08","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}
Aakash Jog, Ron Sverdlov, Silvia Schuster, Adi Avni, Yosi Shacham-Diamand
{"title":"A reversible genetic NOR gate in plants using translational repression.","authors":"Aakash Jog, Ron Sverdlov, Silvia Schuster, Adi Avni, Yosi Shacham-Diamand","doi":"10.1016/j.tibtech.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.004","url":null,"abstract":"<p><p>A proof-of-concept reversible genetic logic circuit in tobacco plants is presented. The genetic circuit implements a Boolean NOR function using a Cas6-based translational repression system, with exposure to estradiol and ethanol as inputs, and expression of GFP as the output. Expressed in the presence of the inducers, two Cas6 proteins are used to selectively prevent the translation of GFP. The circuit yields a 40-90% reduction in GFP expression in the presence of the inducers. A mathematical model of the circuit's mechanism of action is proposed and validated using experimentally acquired data. The employed genetic circuit design methodology is versatile, simplistic, and analogous to PMOS-based pass-transistor logic used in electronic circuit design, making it possible to design complex logic circuits without extensive biological expertise. Lowering the barrier to entry, this methodology can help improve the use of synthetic biology and its integration with other systems.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245337","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}
{"title":"Governance strategies for biological AI: beyond the dual-use dilemma.","authors":"Alex B Lu, Anna C F Lewis","doi":"10.1016/j.tibtech.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.012","url":null,"abstract":"<p><p>A common framing for governing artificial intelligence (AI) in the biological sciences is to focus on risk mitigation owing to the technology's potential 'dual-use' for both beneficial and harmful applications. This is a reactive policy approach, and a broader framing that urges policymakers to actively champion the benefits alongside mitigating risks is needed, including through targeted investments aimed at securing public priorities.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245272","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}
Farhad Nazarian-Firouzabadi, Jianing Bai, Cesar de la Fuente-Nunez
{"title":"Small but mighty: emerging roles of uORFs in plants.","authors":"Farhad Nazarian-Firouzabadi, Jianing Bai, Cesar de la Fuente-Nunez","doi":"10.1016/j.tibtech.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.009","url":null,"abstract":"<p><p>The discovery and manipulation of upstream open reading frames (uORFs) represent a promising frontier in plant biotechnology, offering strategies to enhance disease resistance and crop resilience. Here, we explore the role of uORFs in regulating gene expression under biotic stress and discuss approaches to engineer uORFs for sustainable agriculture and precision breeding.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228633","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}
Tanmay Gupta, Pritish Rath, Viktoriya Pakharenko, Abhijit Vyas, Lena Hofsass, Amirjalal Jalali, Samit Kumar Nandi, Eli D Sone, Subrata Bandhu Ghosh, Sanchita Bandhyopadhyay-Ghosh, Mohini Sain
{"title":"Bioinspired thermoreversible bioink orchestrates focal adhesion-dependent osteogenesis.","authors":"Tanmay Gupta, Pritish Rath, Viktoriya Pakharenko, Abhijit Vyas, Lena Hofsass, Amirjalal Jalali, Samit Kumar Nandi, Eli D Sone, Subrata Bandhu Ghosh, Sanchita Bandhyopadhyay-Ghosh, Mohini Sain","doi":"10.1016/j.tibtech.2025.09.007","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.007","url":null,"abstract":"<p><p>Synergistic integration of bone extracellular matrix (bECM) macromolecules in biomimetic bone tissue engineering (BTE) remains underexplored. This study presents a novel bioink for load-bearing 3D bioprinting (LB-3DBP), comprising gelatin and kappa-carrageenan (κC). Termed 'thermoreversible ionic-covalent entangled (TRICE) bioink', it exhibits exceptional cell viability (>92%), printability, and osteogenic capacity. This advanced multi-material bioprinting approach integrates the TRICE bioink with a calcium phosphate (CaP)-based load-bearing ink. The resulting LB-3DBP scaffolds exhibited a compressive modulus of ~33.2 MPa (comparable with trabecular bone) and up to 200-fold greater strength compared with hydrogel-only bioprints. The (ECM)-inspired TRICE bioink enhanced focal adhesion, proliferation, and MAPK/ERK-mediated osteogenic differentiation. In rabbit femoral condyle models, LB-3DBP scaffolds promoted de novo bone formation and remodeling within 8 weeks. This work bridges mechanical resilience and bioactivity in BTE, offering fully bioresorbable, patient-specific scaffolds that recapitulate the properties of native bone. Thus, our biomimetic, multi-material platform provides a scalable solution for personalized bone regeneration.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226088","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}
Jim Koldenhof, Marianne C Verhaar, Rosalinde Masereeuw, Gisela G Slaats, Anne Metje van Genderen
{"title":"How a kidney microenvironment atlas can advance kidney tissue engineering.","authors":"Jim Koldenhof, Marianne C Verhaar, Rosalinde Masereeuw, Gisela G Slaats, Anne Metje van Genderen","doi":"10.1016/j.tibtech.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.09.002","url":null,"abstract":"<p><p>Despite advances in cellular knowledge through kidney cell and protein atlases, tissue-engineered kidney models remain functionally incomplete. A major gap lies in our limited knowledge of the extracellular matrix (ECM) and the mechanical properties of the kidney microenvironment - key factors that influence cell behavior, differentiation, and function. Current data, that are often based on animal models, lack human-specific, segment-level, and disease-related insights regarding the ECM and mechanical properties. To close this gap, we propose the development of a segment-specific Kidney Microenvironment Atlas: a comprehensive resource that details ECM composition, mechanical characteristics, disease-associated changes, interspecies differences, and measurement techniques. This atlas will inform the creation of more physiologically accurate in vitro models, and thus enhance disease modeling, drug testing, and future clinical applications.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226151","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}
{"title":"Large-scale manufacturing of human gallbladder epithelial cell products and derived hepatocytes via a chemically defined approach.","authors":"Fei Chen, Zijun Wang, Hao Yao, Qinggui Liu, Yuwen Gan, Shoujia Xu, Haili Bao, Yiqiang Jin, Yi-Ping Hu, Junling Gao, Shaohua Song, Min-Jun Wang","doi":"10.1016/j.tibtech.2025.04.009","DOIUrl":"10.1016/j.tibtech.2025.04.009","url":null,"abstract":"<p><p>Manufacturing sufficient quantities of high-quality hepatocytes holds significant promise for the treatment of liver diseases and drug screening. Here, we developed a chemically defined, animal-free method for the large-scale production of human gallbladder epithelial cells (hGBECs) under good manufacturing practice conditions, enabling their clinical application. The cell products were characterized for growth ability, phenotype, freeze-thaw viability, genetic stability, biological contamination, tumorigenicity, and acute toxicity to ensure quality control and biological safety. We also provide a protocol for generating functional hepatocytes from hGBECs. The derived hepatocytes demonstrated typical liver functions, including albumin secretion, urea production, and drug metabolism. In addition, these cells were used in drug toxicity testing. We conducted further functional experiments on Cu<sup>2+</sup> transport and alcohol metabolism. Transplantation of these cells in vivo was able to rescue mice from liver failure. This large-scale, convenient strategy for manufacturing hGBECs serves as a biobank for clinical applications and provides a valuable model for studying liver diseases.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2646-2664"},"PeriodicalIF":14.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120951","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}
Trends in biotechnologyPub Date : 2025-10-01Epub Date: 2025-05-19DOI: 10.1016/j.tibtech.2025.04.006
Ondrej Pencik, Martina Kolackova, Katarina Molnarova, Dalibor Huska
{"title":"What would a hypothetical supercyanobacterium look like?","authors":"Ondrej Pencik, Martina Kolackova, Katarina Molnarova, Dalibor Huska","doi":"10.1016/j.tibtech.2025.04.006","DOIUrl":"10.1016/j.tibtech.2025.04.006","url":null,"abstract":"<p><p>Over the past two decades, advances in molecular and microbiological methods have broadened the range of microorganisms used in biotechnology. Among them, phototrophic bacteria - especially cyanobacteria - are gaining attention for their potential in tackling climate change and producing biopharmaceuticals. While traditional strains such as Escherichia coli and Bacillus subtilis dominate the field, cyanobacteria offer unique features that present both challenges and opportunities, such as complex gene regulation linked to photosynthesis and carbon fixation, protein sorting, and secretion, as well as the ability to establish novel symbiotic partnerships. This review highlights key developments in engineering cyanobacteria and outlines a vision for a future 'supercyanobacterium' that combines the best traits of current strains, unlocking new possibilities in heterotrophy-dominated biotechnology.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2410-2426"},"PeriodicalIF":14.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112166","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}
Trends in biotechnologyPub Date : 2025-10-01Epub Date: 2025-05-19DOI: 10.1016/j.tibtech.2025.04.015
Defne Yigci, Önder Ergönül, Savas Tasoglu
{"title":"Mpox diagnosis at POC.","authors":"Defne Yigci, Önder Ergönül, Savas Tasoglu","doi":"10.1016/j.tibtech.2025.04.015","DOIUrl":"10.1016/j.tibtech.2025.04.015","url":null,"abstract":"<p><p>The increasing number of Monkeypox (Mpox) cases in non-endemic countries resulted in the WHO declaring a public health emergency of international concern. Accurate and timely diagnosis of Mpox has a critical role in containing the spread of infection. Diagnosis currently relies on PCR, which requires trained personnel and complex laboratory infrastructure. Thus, the development of point-of-care (POC) tools are essential to facilitate rapid, accurate, and user-friendly diagnosis. Here, we review POC diagnostic tools available for Mpox. We also discuss bottlenecks preventing the widespread implementation of POC platforms for Mpox diagnosis and potential strategies to address these limitations. Furthermore, we describe future directions, including the role of machine learning (ML) and deep learning (DL)-based models and the integration of integrated field-deployable platforms for Mpox diagnosis.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2427-2439"},"PeriodicalIF":14.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112159","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}