{"title":"CRISPR genome editing in plants without tissue culture.","authors":"Chao Li, Desheng Mei, Hongtao Cheng, Xiaoping Pan, Baohong Zhang","doi":"10.1016/j.tibtech.2025.12.017","DOIUrl":"10.1016/j.tibtech.2025.12.017","url":null,"abstract":"<p><p>Conventional plant genome editing relies on tissue culture-mediated somatic cell regeneration, a technically demanding process that limits its application across diverse species. Emerging strategies now circumvent this bottleneck by enabling direct genome editing of meristematic or germline cells. Key advances include (i) genome editing via de novo meristem induction or dormant meristem activation; (ii) germline editing facilitated by graft-mobile tRNA-like sequence systems and haploid induction technologies; and (iii) optimized viral delivery platforms that exploit mobile RNA elements and compact editors such as TnpB to achieve efficient, transgene-free, heritable modifications across a broad range of genotypes and species. The development of robust, tissue culture-free editing platforms promises to revolutionize crop improvement pipelines and accelerate trait development for sustainable agriculture.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2611-2628"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214366","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":"Engineering Bacillus subtilis as a sustainable platform for the production of functional bile acids.","authors":"Yingchao Zang, Zhongpeng Guo, Rodrigo Ledesma-Amaro, Yu Xin, Yaokang Wu, Zhenghua Gu, Liang Zhang","doi":"10.1016/j.tibtech.2026.03.021","DOIUrl":"10.1016/j.tibtech.2026.03.021","url":null,"abstract":"<p><p>Bile acids and their derivatives are key regulators of host metabolism, immunity, and microbiome interactions, with growing therapeutic potential. Conventional production methods of bile acids relying on animal extraction or chemical synthesis are inefficient, costly, and environmentally unfriendly. Microbial synthesis offers a sustainable alternative but is limited by the absence of genetic tools for native anaerobic producers. Here, we reconstructed the bile acid 7α-dehydroxylation pathway in Bacillus subtilis, a safe and tractable host. We characterized the key Bai enzymes and performed comprehensive analyses of the bile acids generated through in vitro assays and whole-cell catalysis. Multiple intermediates and end products, including cholyl-CoA, 3-oxo-cholic acid, 3-oxo-4,5-6,7-didehydro-deoxycholic acid, 3-oxo-4,5-dehydro-deoxycholic acid, 3-oxo-deoxycholic acid, and deoxycholic acid, were identified. This work establishes a functional heterologous platform for bile acid biosynthesis, enabling sustainable production and future applications in therapeutics and microbiome engineering.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2679-2698"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699809","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 : 2026-09-01Epub Date: 2026-04-15DOI: 10.1016/j.tibtech.2026.03.014
Zheng Qin, Lei Cao, Chang Liu, Yong An, Fangshuo Li, Xipeng Yang, Guoqiang Chen, Mengyuan Qian, Yan Zhang, Jun Yang
{"title":"Cadherin-engineered microspheres enable scalable biofabrication of multilineage liver organoids.","authors":"Zheng Qin, Lei Cao, Chang Liu, Yong An, Fangshuo Li, Xipeng Yang, Guoqiang Chen, Mengyuan Qian, Yan Zhang, Jun Yang","doi":"10.1016/j.tibtech.2026.03.014","DOIUrl":"10.1016/j.tibtech.2026.03.014","url":null,"abstract":"<p><p>Reproducing the spatiotemporally coordinated emergence of vascular, biliary, and parenchymal compartments of the human liver remains a persistent bottleneck in organoid engineering. We introduce biodegradable poly(lactic-co-glycolic acid) microspheres that display epithelial (E) cadherin and vascular endothelial (VE) cadherin fusion proteins and deliver morphogens, mimicking key developmental signals that guide liver organogenesis. When combined with mesenchymal stem cells (MSCs), the microspheres supply adhesion cues that drive aggregate compaction. E-cadherin engagement induces Yes-associated protein activation, priming MSCs for lineage induction. Complementarily, VE-cadherin and vascular endothelial growth factor jointly establish an endothelial niche that delivers inductive cues for hepatic lineage divergence. The resulting organoids display compartmentalized architecture comprising hepatocytes, cholangiocytes, mesenchymal cells, and endothelial networks and respond to hepatotoxic compounds with clinically relevant phenotypes. Unlike induced pluripotent stem cell-based or multiple cell cocultures, this single-source MSC system achieves self-organization through cadherin-defined adhesion and timed morphogen delivery. These elements define a scalable, cadherin-defined biomaterial platform for liver organoid engineering, enabling translational use in drug evaluation and regenerative medicine.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2744-2770"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699837","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 : 2026-09-01Epub Date: 2026-02-19DOI: 10.1016/j.tibtech.2025.12.029
Muhammad Waqas, Chen Yaning, Yong-Ling Ruan, Zi-Ming Ren, Mark Stitt, Christoph-Martin Geilfus
{"title":"Trehalose 6-phosphate as master switch for optimizing crop yield and resilience.","authors":"Muhammad Waqas, Chen Yaning, Yong-Ling Ruan, Zi-Ming Ren, Mark Stitt, Christoph-Martin Geilfus","doi":"10.1016/j.tibtech.2025.12.029","DOIUrl":"10.1016/j.tibtech.2025.12.029","url":null,"abstract":"<p><p>Crop breeding faces the challenge of balancing yield with resource efficiency and stress tolerance. The key regulatory metabolite trehalose 6-phosphate (T6P) integrates carbon status with growth and stress responses. Manipulating T6P levels through genetic modification or chemical intervention provides a powerful tool to tackle the growing challenges of crop production.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2506-2510"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258904","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 : 2026-09-01Epub Date: 2026-03-17DOI: 10.1016/j.tibtech.2025.12.027
Mónica Garcés-Ruiz, Belén Guijarro Díaz-Otero, Livio Antonielli, João Pedro Saraiva, Dimitrios Karpouzas, Stéphane Declerck
{"title":"Machine learning for designing low-risk microbial consortia pesticides.","authors":"Mónica Garcés-Ruiz, Belén Guijarro Díaz-Otero, Livio Antonielli, João Pedro Saraiva, Dimitrios Karpouzas, Stéphane Declerck","doi":"10.1016/j.tibtech.2025.12.027","DOIUrl":"10.1016/j.tibtech.2025.12.027","url":null,"abstract":"<p><p>Microbial consortia, considered low-risk pesticides (LRPs), appear to be valuable tools for reducing our dependence on chemical pesticides. However, their use is limited by inconsistent product efficacy and registration difficulties. Artificial intelligence (AI) and machine learning (ML) offer solutions for designing and evaluating synthetic microbial communities (SynComs), predicting their compatibility, ecological stability, and biocontrol efficacy. The transition from laboratory discovery of SynCom-based LRPs to field application and commercialization could be significantly accelerated. Here, we review the methods and steps necessary to establish reliable SynComs and describe how AI and ML approaches could improve the construction and validation of SynCom-based LRPs to obtain more specific results that can contribute to their risk assessment.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2596-2610"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481676","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":"A universal light-controlled highly sensitive one-pot CRISPR/Cas12a diagnostic based on structure-engineered crRNA.","authors":"Jieyu Cui, Lulu Zhang, Jing Zhou, Ting Shi, Shangyi Wu, Tenghui Dai, Lijun Hao, Junjie Pan, Xiaodan Lai, Wentao Lu, Xingxu Huang, Zhanjun Li, Liangxue Lai, Xinjie Wang","doi":"10.1016/j.tibtech.2026.03.018","DOIUrl":"10.1016/j.tibtech.2026.03.018","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR)-based nucleic acid detection has transformed molecular diagnostics through its speed and accuracy; however, one-pot formats are often limited by sensitivity and field suitability. Herein, we developed a universal light-controlled high-sensitivity one-pot CRISPR/Cas12a testing (ULTRAt) platform based on structure-engineered CRISPR RNA (crRNA) scaffolds. By incorporating photocaged 6-nitropiperonyloxymethyl groups into the crRNA stem-loop, Cas12a activity is transiently suppressed during isothermal amplification via structural modulation, enabling efficient target enrichment. Subsequent UV irradiation removes the protecting groups, restoring the native conformation and activating robust trans-cleavage. ULTRAt achieves a limit of detection of two copies of monkeypox virus per reaction with a 15-min time-to-result, representing a 100-fold sensitivity improvement over conventional assays. The platform further supports single-nucleotide polymorphism discrimination and human papillomavirus 16/18 genotyping. Analysis of 91 clinical samples demonstrates strong concordance between ULTRAt and reference qPCR and sequencing assays. Collectively, ULTRAt enables rapid, ultra-sensitive, and versatile one-pot detection, supporting near-patient diagnostics and genotyping.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2699-2721"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676988","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 : 2026-09-01Epub Date: 2026-03-23DOI: 10.1016/j.tibtech.2025.12.021
Cai-Yun Wu, Man-Man Xu, Jie Li, Tian-Qiong Shi
{"title":"Paenibacillus polymyxa cell factories for production of polymyxins.","authors":"Cai-Yun Wu, Man-Man Xu, Jie Li, Tian-Qiong Shi","doi":"10.1016/j.tibtech.2025.12.021","DOIUrl":"10.1016/j.tibtech.2025.12.021","url":null,"abstract":"<p><p>Polymyxins synthesized by Paenibacillus polymyxa are critical for the treatment of multidrug-resistant infections, but production suffers from low yield and high cost. This forum article focuses on strategies for engineering P. polymyxa cell factories by optimizing genetic transformation systems, gene editing tools, and metabolic engineering strategies to enable sustainable polymyxin production.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2501-2505"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504766","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 : 2026-09-01Epub Date: 2026-02-16DOI: 10.1016/j.tibtech.2025.12.020
Zhengshui Xu, Yu Li, Yundong Zhou, Changchun Ye, Junjie Kuang, Chengliang Yin, Danwen Zhao, Hui Guo, Narmatha Chellamani, Manimurugan Shanmuganathan, João Conde, Shiyuan Liu
{"title":"Advancements and challenges in CAR-NK cell therapy for cancer treatment.","authors":"Zhengshui Xu, Yu Li, Yundong Zhou, Changchun Ye, Junjie Kuang, Chengliang Yin, Danwen Zhao, Hui Guo, Narmatha Chellamani, Manimurugan Shanmuganathan, João Conde, Shiyuan Liu","doi":"10.1016/j.tibtech.2025.12.020","DOIUrl":"10.1016/j.tibtech.2025.12.020","url":null,"abstract":"<p><p>Chimeric antigen receptor natural killer (CAR-NK) cell therapy is an emerging cancer treatment offering advantages over CAR-T therapy, including reduced risks of cytokine release syndrome and graft-versus-host disease. This review highlights how genetic engineering enhances natural killer cells' innate tumor-killing abilities through CAR expression. Preclinical and clinical studies show promising antitumor responses, yet challenges remain, such as ensuring in vivo persistence, overcoming the immunosuppressive tumor microenvironment, and addressing manufacturing hurdles. Strategies such as cytokine support, combination therapies, and novel CAR designs are explored to improve efficacy. Future directions include personalized approaches, novel antigen targets, and artificial intelligence integration. CAR-NK therapy holds strong potential as a safe, scalable, and effective modality in cancer immunotherapy.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2511-2529"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146214397","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 : 2026-09-01Epub Date: 2026-04-10DOI: 10.1016/j.tibtech.2026.03.015
Fan Ding, Jingjing Xu, Yue Ma, Zhaoyang Yao, Jia Gao, Kangni Shang, Karsten Haupt, Guoqing Pan
{"title":"Dynamic control of integrin signaling for cell manipulation via molecularly imprinted decoy receptor.","authors":"Fan Ding, Jingjing Xu, Yue Ma, Zhaoyang Yao, Jia Gao, Kangni Shang, Karsten Haupt, Guoqing Pan","doi":"10.1016/j.tibtech.2026.03.015","DOIUrl":"10.1016/j.tibtech.2026.03.015","url":null,"abstract":"<p><p>Integrin plays a crucial role in human immune system activation and stem cell differentiation through interactions with the extracellular matrix (ECM). Reversible modulation of integrin signaling has illuminated the road toward broad-spectrum disease treatment and tissue regeneration. In this regard, an integrin-like decoy receptor, termed molecularly imprinted polymer (MIP), was synthesized via solid-phase imprinting to target the Arg-Gly-Asp (RGD) sequence, an integrin-binding motif abundantly present in the ECM. The MIP, with temperature-dependent RGD affinity, enabled dynamic intervention in integrin signaling, thereby modulating integrin-RGD-mediated immune response and cell differentiation. The MIP could, on demand, orchestrate macrophage phenotypes to display proinflammatory or anti-inflammatory traits, potentially beneficial at the early stage of tissue injury. Furthermore, stem cell fates could be controlled by MIP, showing potential to prevent hyperplasia caused by excessive differentiation. The proof-of-concept studies demonstrate the feasibility of MIP-based decoy receptors in the dynamic control of integrin signals and cell evolution, showing promise in tissue repair and related diseases.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2796-2811"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676986","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 : 2026-09-01Epub Date: 2026-01-23DOI: 10.1016/j.tibtech.2025.12.012
Qihang Chen, Changtai Zhang, Song Liu, Weizhou Zeng, Jingwen Zhou
{"title":"Metabolic and enzyme engineering for steroid hormone biosynthesis.","authors":"Qihang Chen, Changtai Zhang, Song Liu, Weizhou Zeng, Jingwen Zhou","doi":"10.1016/j.tibtech.2025.12.012","DOIUrl":"10.1016/j.tibtech.2025.12.012","url":null,"abstract":"<p><p>Steroid hormones are key signaling molecules regulating growth, metabolism, reproduction, and stress adaptation and are widely used as essential pharmaceuticals. Traditional production from sterol feedstocks through multistep chemical or microbial transformations is limited by inefficiency and scalability. Recent advances in synthetic biotechnology enable de novo biosynthesis of steroid hormones from simple carbon sources in yeasts and fungi. This review highlights metabolic rewiring to increase flux, cytochrome P450 enzyme engineering for side-chain cleavage, and hydroxylation to overcome rate-limiting bottlenecks of steroid hormone biosynthesis. We also discuss strategies to redesign steroid-transport pathways to alleviate intracellular accumulation and improve membrane export. Looking ahead, we envision integrating metabolic, enzyme, and transport engineering to build a scalable, data-driven 'intelligent' platform for sustainable steroid hormone biomanufacturing.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"2545-2562"},"PeriodicalIF":16.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044091","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}