Journal of Biological Engineering最新文献

{"title":"UniSePT: an engineered broadly applicable Unique Secretory signal PepTide for high-yield biotherapeutic production in mammalian cell-based expression systems.","authors":"Goutam Ulgekar, Satarupa Dutta, Ealisha Jain, Meenakshi Mansukhani, Harshada Thawari, Subeer S Majumdar, Nirmalya Ganguli","doi":"10.1186/s13036-026-00704-2","DOIUrl":"10.1186/s13036-026-00704-2","url":null,"abstract":"<p><strong>Background: </strong>The yield of therapeutic proteins in mammalian cell-based production systems is often limited by inefficient secretion and reduced bioactivity caused by incompatible secretory signal peptides (SPs). Therefore, a broadly applicable signal peptide that can be fused to different proteins of interest to enhance their secretion and overall production is needed.</p><p><strong>Results: </strong>To address this challenge, we engineered a robust, broadly applicable Unique Secretory signal PepTide (UniSePT) by combining SP sequences from β-casein (CSN2) and β-lactoglobulin (BLG) proteins of Indian river buffalo. UniSePT demonstrated higher secretion efficiency than commonly used SPs, such as human serum albumin and preproinsulin SP. Importantly, this improved secretion does not compromise the bioactivity of the therapeutic proteins produced. Additionally, UniSePT showed minimal cleavage variability, supporting its compatibility with various therapeutic proteins.</p><p><strong>Conclusion: </strong>The newly developed UniSePT enhances the titer and bioactivity of therapeutic proteins in mammalian expression systems. Its broad applicability and improved secretion efficiency make it a promising tool for industrial-scale production, potentially reducing the cost of therapeutic protein production.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clitocine suppresses TNBC progression by boosting CCRL2 to block survival signals and neutrophil-driven inflammation.","authors":"Qi Chen, Yanyun Ruan, Shuanshuan Liu, Hozeifa M Hassan, Shaoyin Bao, Weiliang Liu, Jianguo Sun, Hongsheng Lu","doi":"10.1186/s13036-026-00707-z","DOIUrl":"10.1186/s13036-026-00707-z","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the anti-tumor mechanisms of clitocine, a natural compound, in triple-negative breast cancer (TNBC), with a focus on its role in modulating the immune microenvironment via C-C motif chemokine receptor like 2 (CCRL2). The anti-cancer effects of clitocine were assessed in vitro using TNBC cell lines (MDA-MB-231 and MDA-MB-468) through functional assays, flow cytometry, and immunoblotting. RNA sequencing was performed to identified clitocine-induced transcriptional changes. The subcutaneous 4T1 xenograft models in BALB/c mice were used for in vivo validation. Additionally, mass cytometry (CyTOF) profiled tumor immune infiltration in tumor tissues, and the role of CCRL2 in modulating the tumor immune microenvironment and inflammatory pathways was investigated through database mining (TCGA) and gain/loss-of-function experiments.</p><p><strong>Results: </strong>Clitocine potently inhibits TNBC cell proliferation, metastasis, and epithelial-mesenchymal transition (EMT), while inducing mitochondrial apoptosis. It alters cancer-related gene expression (upregulating CCRL2), suppresses PI3K-AKT, NFκB, and ERK pathways, and exhibits potent antitumor activity in vivo without systemic toxicity. Mechanistically, clitocine remodels the tumor immune microenvironment by reducing neutrophil infiltration and suppressing neutrophil extracellular traps (NETs) formation, effects mediated through the CCRL2/chemerin axis. Furthermore, CCRL2 is identified as a tumor suppressor, with low expression in TNBC patients correlating with poor survival. Credibly, CCRL2 knockdown in vitro and in vivo significantly abrogates the anti-tumor and immunomodulatory effects of clitocine.</p><p><strong>Conclusion: </strong>Our findings demonstrate that clitocine exerts potent anti-TNBC effects by upregulating CCRL2 expression, thereby activating the clitocine/CCRL2/chemerin axis. This axis disrupts critical oncogenic signaling pathways and reprograms the immunosuppressive tumor microenvironment.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering a PD-L1-sensing synthetic receptor for programmable macrophage response.","authors":"Ilaria De Martino, Luigi Russo, Matteo Marchetti, Velia Siciliano","doi":"10.1186/s13036-026-00708-y","DOIUrl":"10.1186/s13036-026-00708-y","url":null,"abstract":"<p><p>Cellular decision-making relies on the integration of multiple extracellular cues into coordinated functional responses. Synthetic biology provides tools to rewire this process by engineering receptors that convert defined inputs into programmable outputs. Here, we describe a synthetic receptor-based architecture that enables monocytic-like cells to sense an immune-regulatory ligand and conditionally activate a phagocytic program. We engineered a synthetic Notch-based receptor (SNIPR) that detects programmed death-ligand 1 (PD-L1), a broadly expressed immune-regulatory ligand. Upon PD-L1 engagement, the circuit triggers programmable outputs, including expression of a fluorescent reporter or CV1-Fc, as model effector that interferes with CD47-mediated inhibition of phagocytosis. We show that circuit activation scales with PD-L1 levels, partially attenuates PD-1/PD-L1 signaling, and that conditional CV1-Fc expression enhances engulfment of SKOV-3 ovarian cancer cells by THP-1-derived macrophages in vitro. Collectively, this work reframes PD-L1 from an end-point therapeutic target to a programmable input signal for synthetic circuit activation and establishes a modular framework for ligand-responsive control of engineered macrophage behaviour.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell research and regenerative medicine: meeting report from the Royan International Stem Cell Congress 2025.","authors":"Niloofar Bajool, Mehdi Abdolazimi, Mohsen Razzaznian, Zeinab Zakerian, Sharif Moradi","doi":"10.1186/s13036-026-00702-4","DOIUrl":"10.1186/s13036-026-00702-4","url":null,"abstract":"<p><p>The 21st Royan International Stem Cell Congress (3-5 September 2025, Tehran, Iran) convened the global stem cell community to assess the accelerating translation of regenerative medicine from bench to bedside. Over three days, 10 thematic sessions, spanning pluripotency, cancer, organoid technology, molecular biomedicine, artificial intelligence (AI), bioengineering, and clinical translation, provided a comprehensive overview of a field undergoing increasing integration. Key presentations reported recent progress in several areas: the generation of primate and human embryo models for developmental study; new strategies in cross-species reprogramming and exosome-based therapeutics; and the application of AI for patient stratification, drug repurposing, and metabolic modeling. Concurrently, sessions on bioengineering showcased developments in next-generation biomaterials, non-viral gene delivery systems, and scalable microfluidic platforms aimed at enhancing therapeutic safety and manufacturability. The congress also featured critical discussions on regulatory frameworks, bioentrepreneurship, and the ecosystem required to support clinical adoption. Collectively, the meeting underscored a continuing shift toward a multidisciplinary paradigm in which foundational biology, emerging technology, and pragmatic translation converge to advance the development of safe, effective, and accessible stem cell-based therapies worldwide.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"20 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microengineered bone models: advances and applications of bone-on-a-chip technology.","authors":"Hossein Rayat Pisheh, Ahmad Vaez","doi":"10.1186/s13036-026-00703-3","DOIUrl":"10.1186/s13036-026-00703-3","url":null,"abstract":"<p><p>Bone-on-a-Chip (BoC) platforms are emerging microphysiological systems designed to recapitulate the complex cellular, structural, and mechanical microenvironments of human bone. These microfluidic-based models provide enhanced physiological relevance for studying bone remodeling dynamics, disease progression, and drug responses compared to traditional 2D cultures. This review discusses the anatomical and pathophysiological features of bone that must be replicated in vitro, highlighting recent advances in BoC platforms and their applications in regenerative medicine, drug discovery, and personalized therapy. However, despite their potential, current BoC technologies still face significant challenges, including the simplified representation of the extracellular matrix, incomplete recapitulation of the dense osteocyte network, and partial reproduction of native biomechanical stimuli. Furthermore, integrating vascularization, immune components, and ensuring scalability remain critical hurdles. Future directions focus on developing multi-tissue interfaces, advanced biomaterials, real-time sensing technologies, and AI-assisted data analysis. While still evolving, BoC technology serves as a promising tool for bridging the gap between in vitro models and clinical applications in translational bone research.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13445809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunable PEGylation platform for efficient siRNA delivery using mesoporous silica nanoparticles.","authors":"Taeho Kim, Dongseong Seo, Jonghyun Park, Dongmin Yu, Chanju Choi, Sohyeon Yu, Jeongmin Shin, Simseok A Yuk, Daekyung Sung, Hyungjun Kim","doi":"10.1186/s13036-026-00701-5","DOIUrl":"10.1186/s13036-026-00701-5","url":null,"abstract":"<p><p>Poly(ethylene glycol) (PEG) coatings are widely used to improve nanoparticle stability and biocompatibility, yet conventional PEGylation methods rely on multi-step conjugation that limits reproducibility and restricts control over charge-shielding balance critical for siRNA delivery. Here, we present a composition-tunable PEGylation strategy based on poly(2-(dimethylamino)ethyl methacrylate-co-poly(ethylene glycol) methacrylate) (poly(DMAEMA-co-PEGMA), hereafter referred to as AP) copolymers for the efficient delivery of PD-L1 siRNA using mesoporous silica nanoparticles (MSNs). Copolymers with varying DMAEMA: PEGMA ratios (2:1, 1:1, 0.5:1) and PEG chain lengths (Mn 450 or 950 Da) were synthesized via one-step free-radical polymerization, enabling precise tuning of surface charge and steric stabilization. The optimized MSN/copolymer complexes exhibited enhanced siRNA loading, colloidal stability, and serum resistance while maintaining favorable cytocompatibility. Cellular studies demonstrated improved uptake and significant PD-L1 gene silencing. This work establishes a composition-tunable and scalable PEGylation platform that overcomes the limitations of conventional surface modification and provides a potential strategy for siRNA-based applications.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of heterologous lactate dehydrogenase expression in Ogataea polymorpha for enhanced L-Lactic acid production.","authors":"Aksyniia Tsaruk, Justyna Ruchala, Roksolana Vasylyshyn, Kostyantyn Dmytruk, Andriy Sibirny","doi":"10.1186/s13036-026-00699-w","DOIUrl":"10.1186/s13036-026-00699-w","url":null,"abstract":"<p><p>Lactic acid (LA) is a key platform chemical with broad industrial applications, including biodegradable plastics and pharmaceuticals. While microbial fermentation enables the sustainable production of optically pure L-lactic acid, challenges persist in substrate flexibility and process optimisation. Thermotolerant methylotrophic yeast Ogataea polymorpha has been tested as an alternative biocatalyst for sustainable production of lactic acid, a key platform compound for bioplastics and green manufacturing. However, the influence of lactate dehydrogenase (LDH) origin on metabolic flux redirection in this chassis has not been systematically investigated. This study presents the first comparative evaluation of heterologous LDHs from fungal, bacterial, protistan and mammalian sources expressed in O. polymorpha and assessed across four carbon substrates (glucose, xylose, glycerol, and methanol). The recombinant strains were evaluated for lactic acid production on glucose, xylose, and methanol under various aeration and pH-controlled conditions. Among the tested constructs, the LDH_Bt strain expressing bovine LDH exhibited the highest lactic acid titres from glucose (up to 72.6 g/L), particularly under neutralised conditions with CaCO₃, while LDH_Ro achieved the highest titre on xylose under high agitation with a neutraliser (9.59 g/L). Under methanol-based conditions, LDH_Pf produced the highest titre among the strains under pH-controlled, low-agitation conditions (1.12 g/L). However, the highest absolute methanol-derived titre was observed for LDH_Lp at 220 rpm without CaCO₃ supplementation (1.27 g/L). Despite having an intact ethanol biosynthesis pathway, the obtained transformants produced very low amounts of ethanol (typically below 0.3 g/L, with occasional higher values depending on fermentation conditions). Lactic acid formation from xylose, glycerol, and methanol was notably lower compared to glucose, indicating substrate-dependent redox and compartmentalisation constraints. A weak-to-moderate association between LDH transcript level and lactic acid titre was observed, suggesting that expression contributes to flux control but does not solely determine pathway efficiency. These findings demonstrate that enzyme origin and substrate context jointly define metabolic output and highlight O. polymorpha as a promising platform for thermotolerant lactic acid bioproduction.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148054615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization of novel bigel systems based on natural gums: rheological, textural, and thermal properties.","authors":"Zohreh Baratian Ghorghi, Mohammad Ali Hesarinejad, Ali Faezian, Samira Yeganehzad","doi":"10.1186/s13036-026-00689-y","DOIUrl":"10.1186/s13036-026-00689-y","url":null,"abstract":"<p><p>The fabrication of novel bigel formulations utilizing natural gums presents an attractive and valuable approach for the development of healthy and functional food products. The goal of the current investigation was to establish new bigel systems incorporating various hydrogels matrices, specifically alginate (ALG), basil seed gum (BSG), and Alyssum homolocarpum seed gum (AHSG) at different mixing oleogel/hydrogel ratios (100:0, 99:1, 95:5, and 90:10). Initially, the flow behavior characteristics of different concentrations of ALG (2% w/w), AHSG (0.25, 0.50, 0.75, and 1.0% w/w), and BSG (1.0, 1.5, and 2.0% w/w) were determined to identify the optimal hydrogel concentration for bigel fabrication. The rheological analysis confirmed that all tested hydrogel concentrations exhibited shear-thinning non-Newtonian behavior (power law index, n < 1). Subsequently, the viscoelastic properties of the oleogel and ALG-bigel samples were characterized. The results indicated that the bigel systems displayed a dominant solid-like network structure over a liquid-like behavior, evidenced by the storage modulus (G') consistently exceeding the loss modulus (G\"). No significant alterations were observed in the mean particle size or morphological characteristics of the bigels (p > 0.05). Furthermore, the thermal stability of the bigels' network matrix demonstrated an increase proportional to the increase in the hydrogel fraction incorporated into the system. Textural profile analysis revealed that the hardness and adhesiveness of the fabricated bigels ranged from 319.87 to 472.27 gf and 143.07 to 242.23 gf.s, respectively. In conclusion, these findings confirm that the natural hydrocolloids AHSG and BSG can effectively mimic the structural and functional role of alginate hydrogel in the bigel systems.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host cell protein impurities in therapeutic proteins: overview of advances in detection, nonconventional removal technologies and immunogenicity assessment.","authors":"Sakhr Alhuthali, Syazana Mohamad Pauzi, Cleo Kontoravdi","doi":"10.1186/s13036-026-00685-2","DOIUrl":"10.1186/s13036-026-00685-2","url":null,"abstract":"<p><p>Therapeutic proteins, particularly monoclonal antibodies, represent a cutting-edge technology for combating chronic illnesses. These biomolecules are produced in cell-based expression systems that generate thousands of impurities, which must be removed through a sequence of chromatographic and filtration steps to ensure drug efficacy and patient safety. Host cell proteins (HCPs) are among the most concerning impurities, due to quantification challenges, their physicochemical diversity, and their potential to affect drug stability and increase immunogenicity. Tracking and removing HCPs remains a perpetual industrial goal and a growing topic of discussion in the biotechnology industry and amongst regulators. In this review, we provide a comprehensive overview of the research about HCPs in biopharmaceutical processes, highlighting gaps in process analytics, process design, and impurity risk assessment. We summarise the challenges and recent progress in HCP detection and quantification, with extensive focus on LC-MS workflows. We next examine methods to reduce HCPs in the upstream process, followed by an overview of emerging purification technologies. Finally, we review some experimental and computational tools for predicting product immunogenicity and optimising manufacturing processes. This review focuses on advances made in the past five years and is intended to support decision-making in therapeutic protein manufacturing.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13288815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-genus phage design through branching domain and conserved peptide interactions.","authors":"Agnieszka Latka, Dorien Dams, Lennert Scholiers, Britt Van Mieghem, Zuzanna Drulis-Kawa, Yves Briers","doi":"10.1186/s13036-026-00682-5","DOIUrl":"10.1186/s13036-026-00682-5","url":null,"abstract":"<p><strong>Background: </strong>Branched receptor-binding protein (RBP) systems enable bacteriophages to broaden their host range through the incorporation of two or more RBPs. Using the Klebsiella podophages KP32, K11, and KP34 as model systems, we experimentally validated the interaction between the branching domain of the primary RBP (RBP1) and the conserved docking peptide of the secondary RBP (RBP2) as an essential architectural pair enabling dual-RBP incorporation into the virion.</p><p><strong>Results: </strong>Systematic engineering revealed that loss of either of these domains, the branching domain or the conserved peptide, abolishes RBP2 assembly, underscoring their structural role in organizing the branched configuration and demonstrating that the anchor domain is the sole element directly attaching the RBP complex to the virion. Exploiting this interaction, we engineered a chimeric phage based on the Klebsiella phage KP32 scaffold that was capable of cross-genus infection and productive propagation on both Klebsiella and Escherichia hosts. In contrast to previous approaches that required replacement of the entire RBP, the adaptor and nozzle proteins, this strategy achieved host-range reprogramming through modular domain swapping and positional relocation of RBPs (i.e., exchanging RBP1 and RBP2 positions). Conversely, an Escherichia phage K1F scaffold was also successfully engineered to infect Klebsiella.</p><p><strong>Conclusions: </strong>Our study confirms that the RBP branching domain and the conserved peptide function as specific interacting partners. Our findings establish the conserved peptide as a docking element and highlight the structural flexibility of podoviruses to accommodate RBPs from different positional and taxonomic contexts. Collectively, this work provides a mechanistic framework for rational phage engineering and defines a general design principle for generating customized therapeutic phages with an expanded host spectrum, including cross-genus infectivity.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147972712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}