{"title":"Precision public engagement: charting a path forward for biotechnology.","authors":"Anna C F Lewis, Naomi Scheinerman","doi":"10.1016/j.tibtech.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.004","url":null,"abstract":"<p><p>Calls for public engagement in biotechnology governance are ubiquitous but imprecise, leaving practitioners without actionable guidance and allowing institutions to claim engagement benefits without delivering them. We introduce a precision public engagement framework spanning seven dimensions, making choices explicit, enabling accountability, and closing the gap between engagement and legitimacy.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866841","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":"NAMs without context of use slow EU adoption.","authors":"Marco Straccia, Milena Mennecozzi","doi":"10.1016/j.tibtech.2026.08.005","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.005","url":null,"abstract":"<p><p>New approach methodologies are not a separate market or scientific category, but a heterogeneous set of methodologies whose relevance depends on a clearly defined context of use (CoU). The early definition of CoU should guide validation, qualification, and evidence generation to accelerate regulatory adoption across the EU.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841336","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":"Promoter selection reduces phenotypic heterogeneity and improves bioproduction.","authors":"Davina Patel, Kiyan Shabestary, Jiabao Xu, Cinzia Klemm, Wei E Huang, Rodrigo Ledesma-Amaro","doi":"10.1016/j.tibtech.2026.08.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.08.002","url":null,"abstract":"<p><p>Cell-to-cell heterogeneity leads to the formation of subpopulations within an isogenic population, resulting in the coexistence of high and low producer cells. However, the impact of this phenotypic heterogeneity on bioproduction has been overlooked. Using flow cytometry to analyse commonly used yeast promoters, we found that many display macro-heterogeneity, generating multiple discrete subpopulations. Additionally, by regressing single-cell protein expression on single-cell RNA sequencing data, we explored the use of predictive models as a guide for selecting promoters with more homogeneous expression at desired expression levels. As a proof of concept, we engineered an improved lycopene pathway by substituting homogeneous promoters for macro-heterogeneous ones and implemented single-cell Raman spectroscopy to demonstrate up to a threefold increase in single-cell and bulk lycopene production. Overall, our results show that promoter heterogeneity can have a large impact on microbial bioprocesses and that the selection of homogeneous promoters can achieve more efficient production in a metabolically engineered pathway.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832737","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}
Qi Gao, Max L Lee, Meagan Makarczyk, Simon K-H Chow, Bruce A Bunnell, Hang Lin, Stuart B Goodman
{"title":"Organ-on-chip bridging musculoskeletal disease modeling and precision therapeutic discovery.","authors":"Qi Gao, Max L Lee, Meagan Makarczyk, Simon K-H Chow, Bruce A Bunnell, Hang Lin, Stuart B Goodman","doi":"10.1016/j.tibtech.2026.08.003","DOIUrl":"10.1016/j.tibtech.2026.08.003","url":null,"abstract":"<p><p>Musculoskeletal (MSK) disorders remain a leading cause of disability, yet effective disease-modifying therapies are limited by poor translational relevance of conventional models. Organ-on-chip (OoC) technologies have emerged as promising platforms for disease modeling and therapeutic discovery. This review highlights recent advances in patient-derived and induced pluripotent stem cell-based OoC systems, multicellular tissue engineering, biomechanical and immune integration, real-time sensing, and data-driven analytics that enhance physiological relevance and predictive capability. We further discuss automated high-throughput screening and machine learning approaches for scalable drug testing and personalized therapeutic prediction. Finally, we address challenges including reproducibility, vascularization, and standardization, and outline a future roadmap toward precision medicine through intelligent OoC platforms and patient-specific digital twins.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148841361","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}
{"title":"Bioinspired microvascular networks for stroke recovery, cerebral revascularization, and neuroprotection.","authors":"Yuke Xie, Peng Lu, Xiaogang Tang, Cong Yao, Bingsong Gu, Xiaoli Qu, Xianhui Zhang, Yijing He, Yabo Zhang, Zhishuo Ren, Dichen Li, Jiankang He, Mao Mao, Jianhua Peng, Yong Jiang","doi":"10.1016/j.tibtech.2026.07.035","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.035","url":null,"abstract":"<p><p>Cerebral ischemic stroke remains a leading cause of disability, with limited options for restoring cerebral blood flow (CBF) and promoting recovery. This study introduces a leaf-mimetic microvascular network to promote poststroke revascularization. The network uses leaf-venation-inspired microchannel templates to direct cell-hydrogel self-assembly into microvascular networks. In a photothrombotic stroke model, the implanted network integrates with host vessels, enhances neovascularization, improves CBF, reduces infarct volume, improves neuronal survival, and promotes functional recovery. Transcriptomic and histological analyses suggest enrichment of potentially reparative neutrophils and reduced inflammation associated with neutrophil extracellular traps as components of the network-associated immune-vascular response. Blocking neutrophil recruitment attenuates network-mediated neovascularization, whereas local delivery of potentially reparative neutrophils partially restores vascular remodeling. These findings provide a preclinical proof of concept that bioinspired microvascular constructs can promote cerebral revascularization and neuroprotection after stroke, while identifying immune-vascular processes that warrant further mechanistic and translational validation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832729","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":"Erythrocytes as programmable intravascular interfaces for therapeutic delivery.","authors":"Min Zhang, Fei Chen","doi":"10.1016/j.tibtech.2026.07.034","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.034","url":null,"abstract":"<p><p>Erythrocyte-based therapeutic delivery is valued for cargo protection and prolonged circulation, but this passive-carrier focus ignores the programmable intravascular interfaces now possible with erythrocytes. We propose a function-guided framework that matches designs to desired outcomes, serving as a guide to when erythrocytes could be the best choice for use as delivery vehicles.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798391","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 RNA-guided bridge recombinases for precise large-scale genome editing.","authors":"Rui Gao, Jingjing Wei, Chao Sun, Jinxing Liu, Zhenyu Li, Yunjia Li, Qiang Gao, Kecheng Yang, Caixia Gao","doi":"10.1016/j.tibtech.2026.07.025","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.025","url":null,"abstract":"<p><p>Precise manipulation of large DNA fragments in eukaryotic genomes remains limited by the low efficiency and delivery constraints of current multicomponent editing systems. In this study, we engineered an RNA-guided bridge recombinase system through rational mutagenesis and AI-assisted directed evolution, enabling programmable chromosomal rearrangements in both plant and mammalian cells and achieving up to a 29.8-fold increase in activity. In plants, the optimized system mediated precise deletions, insertions, and inversions from 1.8- to 315-kb DNA fragments, with stable editing efficiencies of up to 23.9% in regenerated rice plants. We further generated herbicide-resistant rice through a 315-kb chromosomal inversion that rewired endogenous promoter activity. In mammalian cells, the compact ISCro4 recombinase system was delivered using a single adeno-associated virus vector, thereby supporting efficient genome editing. Together, these results establish bridge RNA-guided recombinases as a versatile platform for programmable chromosome-scale genome engineering, with broad potential for precision breeding and gene therapy.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798386","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":"Building a biotechnology company? Check this Indication Checklist.","authors":"William N Hait","doi":"10.1016/j.tibtech.2026.07.033","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.033","url":null,"abstract":"<p><p>Biotechnology companies must carefully consider the choice of the first disease indication for their new drug. There are several key elements that can help guide this critical decision. Drawing on years of experience, this article provides an 'Indication Checklist' with recommendations designed to help.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798429","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}
Fei Liu, Yanyi Wang, Bin Cui, Yanwen Feng, Jun Yue, Chao Zhong
{"title":"Programmable biofunctionalization of bacterial cellulose via a dynamic co-culture platform.","authors":"Fei Liu, Yanyi Wang, Bin Cui, Yanwen Feng, Jun Yue, Chao Zhong","doi":"10.1016/j.tibtech.2026.07.032","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.032","url":null,"abstract":"<p><p>Programmable biofunctionalization of bacterial cellulose (BC) is promising for constructing engineered living materials, but current microbial co-culture approaches struggle to combine coherent matrix formation, dynamic cultivation, and efficient matrix-associated protein functionalization. In this study, we report a polydopamine (PDA)-mediated, surface-immobilized dynamic co-culture platform that pairs Komagataeibacter rhaeticus for BC production with engineered Pichia pastoris for recombinant protein secretion. PDA-mediated co-immobilization preserves conformal BC growth under agitation while maintaining the functional partner near the forming matrix. Cellulose-binding-domain fusion further retains secreted protein cargoes within the BC network, enabling localized functionalization. The template-guided strategy supports geometry control, construct-size scaling, and incorporation of multiple engineered yeast populations. Modular genetic payloads enable pollutant degradation and enzymatic cascade-based analyte detection. As an application-relevant demonstration, lysostaphin-functionalized BC hydrogels effectively controlled Staphylococcus aureus infection and accelerated wound closure in a diabetic murine model. This work establishes a functionally extensible framework for bioactive BC-based living materials.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798426","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":"Material agency: operationalizing the living/nonliving interface in engineered materials.","authors":"Andrea Belluati","doi":"10.1016/j.tibtech.2026.07.036","DOIUrl":"https://doi.org/10.1016/j.tibtech.2026.07.036","url":null,"abstract":"<p><p>The label 'engineered living materials' groups devitalized mycelium composites with metabolically active biosensors, applying shared metrics to systems with fundamentally different failure modes, safety profiles, and engineering requirements. This forum proposes a four-class operational taxonomy, a Maximum Agency Potential classification principle, and a minimum reporting standard that classify systems by biological agency dependence during use.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798401","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}