Trends in biotechnologyPub Date : 2025-04-01Epub Date: 2024-10-10DOI: 10.1016/j.tibtech.2024.09.016
Jia Qian Tor, Quang Bach Le, Hariharan Ezhilarasu, Weng Wan Chan, Deepak Choudhury
{"title":"Advancements and regulations of biomanufacturing cell-based cartilage repair therapies.","authors":"Jia Qian Tor, Quang Bach Le, Hariharan Ezhilarasu, Weng Wan Chan, Deepak Choudhury","doi":"10.1016/j.tibtech.2024.09.016","DOIUrl":"10.1016/j.tibtech.2024.09.016","url":null,"abstract":"<p><p>Cell-based therapies for cartilage repair, including autologous chondrocyte implantation and allogeneic stem cell treatments, show great promise but face challenges due to high costs and regulatory hurdles. This review summarizes available and investigational products, focusing on allogeneic therapies and the impact of diverse regulatory landscapes on their clinical translation.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"738-741"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406937","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 : 2025-04-01Epub Date: 2024-12-13DOI: 10.1016/j.tibtech.2024.11.010
Alexandra Cleaver, Runpeng Luo, Oliver B Smith, Lydia Murphy, Benjamin Schwessinger, Joseph Brock
{"title":"High-throughput optimisation of protein secretion in yeast via an engineered biosensor.","authors":"Alexandra Cleaver, Runpeng Luo, Oliver B Smith, Lydia Murphy, Benjamin Schwessinger, Joseph Brock","doi":"10.1016/j.tibtech.2024.11.010","DOIUrl":"10.1016/j.tibtech.2024.11.010","url":null,"abstract":"<p><p>Secretion of high-value proteins and enzymes is fundamental to the synthetic biology economy, allowing continuous fermentation during production and protein purification without cell lysis. Most eukaryotic protein secretion is encoded by an N-terminal signal peptide (SP); however, the strong impact of SP sequence variation on the secretion efficiency of a given protein is not well defined. Despite high natural SP sequence diversity, most recombinant protein secretion systems use only a few well-characterised SPs. Additionally, the selection of promoters and terminators can significantly affect secretion efficiency, yet screening numerous genetic constructs for optimal sequences remains inefficient. Here, we adapted a yeast G-protein-coupled receptor (GPCR) biosensor, to measure the concentration of a peptide tag that is co-secreted with any protein of interest (POI). Thus, protein secretion efficiency can be quantified via induction of a fluorescent reporter that is upregulated downstream of receptor activation. This enabled high-throughput screening of over 6000 combinations of promoters, SPs, and terminators, assembled using one-pot Combinatorial Golden Gate cloning. We demonstrate this biosensor can quickly identify best combinations for secretion and quantify secretion levels. Our results highlight the importance of SP optimisation as an initial step in designing heterologous protein expression strategies, demonstrating the value of high-throughput screening (HTS) approaches for maximising secretion efficiency.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"838-867"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824508","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":"CRISPR/Cas: a powerful tool for designing and improving oil crops.","authors":"Lijie Li, Dangquan Zhang, Zhiyong Zhang, Baohong Zhang","doi":"10.1016/j.tibtech.2024.09.007","DOIUrl":"10.1016/j.tibtech.2024.09.007","url":null,"abstract":"<p><p>Improving oil yield and quality is a major goal for crop breeding, and CRISPR/Cas-mediated genome editing has opened a new era for designing oil crops with enhanced yield and quality. CRISPR/Cas technology can not only increase oil production but also enhance oil quality, including enhancing pharmaceutical and health components, improving oil nutrients, and removing allergic and toxic components. As new molecular targets for oil biosynthesis are discovered and the CRISPR/Cas system is further improved, CRISPR/Cas will become a better molecular tool for designing new oil crops with higher oil production, enhanced nutrients, and improved health components. 'CRISPRized' oil crops will have broad applications both in industry (e.g., as biofuels) and in daily human life.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"773-789"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372965","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 : 2025-04-01Epub Date: 2025-02-20DOI: 10.1016/j.tibtech.2025.01.009
Christina Stadlbauer, Marjan De Mey, Katrien Schaubroeck, Nele Buyst, Varsha Paleri, Kristien Hens
{"title":"Art-science collaborations in biotechnology research: a transdisciplinary approach.","authors":"Christina Stadlbauer, Marjan De Mey, Katrien Schaubroeck, Nele Buyst, Varsha Paleri, Kristien Hens","doi":"10.1016/j.tibtech.2025.01.009","DOIUrl":"10.1016/j.tibtech.2025.01.009","url":null,"abstract":"<p><p>While funding agencies promote transdisciplinary approaches, significant barriers persist. Successful transdisciplinary research (TDR) demands embracing different ways of knowing, addressing power imbalances, and accepting slower, more complex research processes. Drawing from the experience with BactoHealing, the authors demonstrate how genuine transdisciplinarity requires courage, trust, and institutional support to challenge traditional frameworks.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"735-737"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473119","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 : 2025-04-01Epub Date: 2024-12-16DOI: 10.1016/j.tibtech.2024.11.017
Wenbin Gong, Zhenni Liu, Yuqiu Wang, Wenbo Huang, Kui Yang, Zhenhai Gao, Kun Guo, Zhengtao Xiao, Wei Zhao
{"title":"Reprogramming of Treg cell-derived small extracellular vesicles effectively prevents intestinal inflammation from PANoptosis by blocking mitochondrial oxidative stress.","authors":"Wenbin Gong, Zhenni Liu, Yuqiu Wang, Wenbo Huang, Kui Yang, Zhenhai Gao, Kun Guo, Zhengtao Xiao, Wei Zhao","doi":"10.1016/j.tibtech.2024.11.017","DOIUrl":"10.1016/j.tibtech.2024.11.017","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated inflammatory disorder of the alimentary tract without exact etiology. Mitochondrial reactive oxygen species (mtROS) derived from mitochondrial dysfunction impair intestinal barrier function, increase gut permeability, and facilitate immune cell invasion, and, therefore, are considered to have a pivotal role in the pathogenesis of IBD. Here, we reprogrammed regulatory T cell (Treg)-derived exosomes loaded with the antioxidant trace element selenium (Se) and decorated them with the synthetic mitochondria-targeting SS-31 tetrapeptide via a peptide linker. This linker can be cleaved by matrix metalloproteinases (MMPs) in inflammatory lesions. This actively targetable exosome-derived delivery system is protected from intestinal inflammation by scavenging excessive mtROS and preventing immunologically programmed cell death pyroptosis, necroptosis, and apoptosis, known as PANoptosis. Our results suggest that this engineered exosome delivery platform represents a promising targeted therapeutic strategy for the treatment of IBDs.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"893-917"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847797","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":"Using synthetic biology to express nitrogenase biosynthesis pathway in rice and to overcome barriers of nitrogenase instability in plant cytosol.","authors":"Yimin Shang, Haowen Shi, Minzhi Liu, Peichun Lan, Deyu Li, Xiaomeng Liu, Minyang Wang, Zhiguo Zhang, Sanfeng Chen","doi":"10.1016/j.tibtech.2024.12.002","DOIUrl":"10.1016/j.tibtech.2024.12.002","url":null,"abstract":"<p><p>Engineering nitrogen fixation in cereals could reduce usage of chemical nitrogen fertilizers. Here, a nitrogenase biosynthesis pathway comprising 13 genes (nifB nifH nifD nifK nifE nifN nifX hesA nifV nifS nifU groES groEL) was introduced into rice by transforming multigene vectors and subsequently by sexual crossing between transgenic rice plants. Genome sequencing analysis revealed that 13 nif genes in F<sub>4</sub> hybrid rice lines L12-13 and L8-17 were inserted at two loci on rice chromosome 1. Eleven nitrogen fixation (Nif) proteins were produced and stable NifDK tetramer was formed in rice cytosol. NifH in rice cytosol was unstable and NifH-S18 was found to be a key residue that conferred susceptibility to proteinase degradation. NifH variants with Fe protein activity and resistance to plant endoproteinase cleavage were obtained. This study provides an efficient approach for introducing multiple nif genes into plants and also helps to pre-evaluate the stability of prokaryotic proteins in plant cytosol.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"946-968"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012335","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 : 2025-04-01Epub Date: 2024-10-26DOI: 10.1016/j.tibtech.2024.09.012
Liya Liang, Huiping Tan, Rongming Liu
{"title":"Emerging gene editing in industrial microbiology beyond CRISPR-Cas9.","authors":"Liya Liang, Huiping Tan, Rongming Liu","doi":"10.1016/j.tibtech.2024.09.012","DOIUrl":"10.1016/j.tibtech.2024.09.012","url":null,"abstract":"<p><p>The CRISPR-Cas9 system has been widely applied for industrial microbiology but is not effective in certain microorganisms. This forum explores the strategies aimed at overcoming these challenges, including the use of the Cas12a system, Cas9 variants, and non-CRISPR techniques, to provide more effective strategies for expanding applications in microbial engineering.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":"742-744"},"PeriodicalIF":14.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508797","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}
Min Tae Park, Amrisha Verma, Clifford A Froelich, Seyed Pouria Motevalian
{"title":"Process and quality considerations for recombinant adeno-associated virus manufacturing platforms.","authors":"Min Tae Park, Amrisha Verma, Clifford A Froelich, Seyed Pouria Motevalian","doi":"10.1016/j.tibtech.2025.02.016","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.02.016","url":null,"abstract":"<p><p>Recombinant adeno-associated virus (AAV) is a prominent gene therapy vector, offering a strong safety profile and sustained gene expression. Scaling up AAV manufacturing remains challenging due to its complex processes, high development costs, and the need for rigorous quality control. This review examines the most common AAV suspension production platforms, specifically transfection, infection, and stable producer cell lines (PCLs). For each platform, a list of common unit operations and typical ranges for critical operating parameters is provided, along with high-level product quality specifications. This review aims to offer insights into the advantages and challenges of each manufacturing platform, providing a framework for accelerated process development and informed selection of suitable production platform based on intended clinical use and target product profile.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731653","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":"Enzyme functional classification using artificial intelligence.","authors":"Ha Rim Kim, Hongkeun Ji, Gi Bae Kim, Sang Yup Lee","doi":"10.1016/j.tibtech.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.03.003","url":null,"abstract":"<p><p>Enzymes are essential for cellular metabolism, and elucidating their functions is critical for advancing biochemical research. However, experimental methods are often time consuming and resource intensive. To address this, significant efforts have been directed toward applying artificial intelligence (AI) to enzyme function prediction, enabling high-throughput and scalable approaches. In this review, we discuss advances in AI-driven enzyme functional annotation, transitioning from traditional machine learning (ML) methods to state-of-the-art deep learning approaches. We highlight how deep learning enables models to automatically extract features from raw data without manual intervention, leading to enhanced performance. Finally, we discuss the discovery of novel enzyme functions and generation of de novo enzymes through the integration of generative AIs and bio big data as future research directions.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744054","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}
Edem Gavor, Yeu Khai Choong, Aditya H Gada, J Sivaraman
{"title":"Challenges and design of nanobodies against arboviruses.","authors":"Edem Gavor, Yeu Khai Choong, Aditya H Gada, J Sivaraman","doi":"10.1016/j.tibtech.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.tibtech.2025.03.002","url":null,"abstract":"<p><p>Nanobodies (Nbs) show promise in combating arboviruses. Their small size and stability enable blood-brain barrier (BBB) penetration, cryptic epitope binding, and reduced antibody-dependent enhancement (ADE). This forum highlights Nb advantages, challenges, and innovative delivery methods, emphasizing their transformative potential in arbovirus therapeutics and diagnostics.</p>","PeriodicalId":23324,"journal":{"name":"Trends in biotechnology","volume":" ","pages":""},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744052","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}