Biotechnology Journal最新文献_第6页

Photo-Crosslinking Aided Hierarchical Assembly of Recombinant Collagen Hydrogels for 3D Bio-Printing 用于生物3D打印的重组胶原水凝胶的光交联辅助分层组装。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70259

Chen Wang, Meng Zhang, Fei Xu

{"title":"Photo-Crosslinking Aided Hierarchical Assembly of Recombinant Collagen Hydrogels for 3D Bio-Printing","authors":"Chen Wang, Meng Zhang, Fei Xu","doi":"10.1002/biot.70259","DOIUrl":"10.1002/biot.70259","url":null,"abstract":"<div>\u0000 \u0000 <p>Collagen is a critical structural and functional protein in extracellular matrix. Recombinant collagen provides key benefits such as virus-free safety, low immunogenicity, solubility, and quality consistency. However, it is still challenge to induce recombinant collagen to form self-supported hydrogels while retaining integrity of triple helix structures and fiber morphology. Here we developed photo-crosslinking assisted hierarchical assembly of recombinant collagen fibers to hydrogel. The processing order of methacryloylation prior to inducing fiber formation of recombinant collagen not only made hydrogel with higher substitution degree, higher storage modulus (<i>G</i>′) and initial shear-thinning stress, but also retained triple helix structure and fiber morphology similar to D-periodic banding pattern of Type I collagen. Under the same concentration, photo-crosslinked methacryloylated recombinant collagen (RCMA) hydrogel presented typical viscoelastic solid behavior with a storage modulus <i>G</i>′ of 102 Pa, while GelMA behaved as a viscous solution without sol–gel transition. Further, the RCMA hydrogel demonstrated robust printability in 3D bio-printing, showing potential for constructing intricate biological architectures. Moreover, NIH-3T3 cell culture demonstrated excellent biocompatibility and negligible cytotoxicity of the RCMA hydrogel, with no adverse effects on cell adhesion or proliferation. In summary, these properties underscore the significant potential of RCMA hydrogel for applications in biomedicine and tissue engineering.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coated Bacterial Vaccine Platform Overcomes Weak Antigen Immunogenicity: A Functional Approach to GnRH-Based Immunocastration 包被细菌疫苗平台克服弱抗原免疫原性：gnrh免疫去势的功能途径。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70263

Inés Harguindeguy, Matías H. Assandri, María Antonieta Daza Millone, Sebastián F. Cavalitto, María de los A. Serradell, Gastón E. Ortiz

{"title":"Coated Bacterial Vaccine Platform Overcomes Weak Antigen Immunogenicity: A Functional Approach to GnRH-Based Immunocastration","authors":"Inés Harguindeguy, Matías H. Assandri, María Antonieta Daza Millone, Sebastián F. Cavalitto, María de los A. Serradell, Gastón E. Ortiz","doi":"10.1002/biot.70263","DOIUrl":"10.1002/biot.70263","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunocastration, a nonsurgical strategy based on active immunization against gonadotropin-releasing hormone (GnRH), effectively suppresses steroidogenesis and spermatogenesis. However, peptide vaccines targeting poorly immunogenic antigens such as GnRH often fail to elicit robust adaptive immune responses, requiring adjuvants or carrier proteins. Previously, we introduced Coated Bacterial Vaccines (CBVs), a platform that uses chemically inactivated Gram-positive bacteria to display recombinant antigens fused to the SlpA carboxy-terminal domain (dSLPA) on their surface. This system leverages natural pathogen-associated molecular patterns (PAMPs) to enhance immunogenicity without additional adjuvants. In this work, we extended the application of the CBVs platform to enhance the immune response against a poorly immunogenic GnRH-based peptide vaccine. GnRH-CBVs were formulated using inactivated <i>Bacillus subtilis</i> var. <i>natto</i> coated with a recombinant GnRH tandem-repeat-dSLPA fusion protein and administered to male BALB/c mice. A chitosan-adjuvanted GnRH-dSLPA formulation served as a positive control. Immunization with GnRH-CBVs could favor a strong Th2-biased humoral response, characterized by predominant IgG1 levels comparable to those achieved with chitosan. The resulting antibodies effectively neutralized endogenous GnRH, reducing steroidogenesis and spermatogenesis and inducing marked testicular histological alterations. These findings support CBVs as a promising strategy to enhance peptide vaccine immunogenicity for veterinary immunocastration.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Butyrate-Producing Bacteria in Intestinal Disease Therapy: Potential and Challenges 肠道疾病治疗中的丁酸产生菌：潜力和挑战。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70260

Fenfen Zhang, Wei Zhang, Xiaoting Ren, Bo Liu, Xiaolun Zhou

{"title":"Butyrate-Producing Bacteria in Intestinal Disease Therapy: Potential and Challenges","authors":"Fenfen Zhang, Wei Zhang, Xiaoting Ren, Bo Liu, Xiaolun Zhou","doi":"10.1002/biot.70260","DOIUrl":"10.1002/biot.70260","url":null,"abstract":"<div>\u0000 \u0000 <p>Butyrate-producing bacteria have emerged as keystone species whose metabolic activity orchestrates host-microbial homeostasis in the human gut. This review synthesizes current understanding of how these anaerobic Firmicutes, including <i>Faecalibacterium prausnitzii</i>, <i>Roseburia spp</i>., and <i>Eubacterium rectale</i>, function as key contributors to intestinal health through convergent mechanisms: serving as the primary energy source for colonocytes, enforcing mucosal hypoxia that excludes facultative pathogens, and modulating immunity via histone deacetylase inhibition and G-protein-coupled receptor signaling. We critically examine the translational trajectory of butyrogenic therapies across inflammatory bowel disease, colorectal cancer, and emerging applications in radiation injury, infection, and graft-versus-host disease. Despite compelling mechanistic rationale and consistent clinical associations linking butyrate-producer depletion with disease activity, therapeutic translation faces formidable bottlenecks: extreme oxygen sensitivity complicates manufacturing; cross-feeding networks necessitate ecological rather than monostrain approaches; and host context determines whether butyrate exerts protective or permissive effects. We evaluate cutting-edge strategies to overcome these barriers, including rationally designed consortia, precision prebiotics, phage-mediated niche engineering, synthetic biology approaches, and AI-guided personalization. By integrating mechanistic insight with translational pragmatism, this review outlines a path toward evidence-based butyrogenic therapies that may complement existing strategies for intestinal disease.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3D Bioprinting for Tumor Microenvironment Reconstruction: Advances, Challenges, and Future Perspectives 3D生物打印用于肿瘤微环境重建：进展，挑战和未来展望。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70267

Ling-Jun Yao, Pei-Lin Xie, Ting-Xuan Huang, Jin-Suo Xiao, Zhen-Tao Zhu, Sui Liu, Ting-Yu Wang, Teng Qi

{"title":"3D Bioprinting for Tumor Microenvironment Reconstruction: Advances, Challenges, and Future Perspectives","authors":"Ling-Jun Yao, Pei-Lin Xie, Ting-Xuan Huang, Jin-Suo Xiao, Zhen-Tao Zhu, Sui Liu, Ting-Yu Wang, Teng Qi","doi":"10.1002/biot.70267","DOIUrl":"10.1002/biot.70267","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer remains a major global health burden, and the disconnect between preclinical models and clinical outcomes continues to hinder progress in oncology. Conventional two-dimensional (2D) cell cultures fail to recapitulate the in vivo tumor microenvironment (TME) and consequently show poor predictive power for drug responses. Animal models provide systemic insights but are constrained by interspecies differences, limited throughput, and high costs. Advanced three-dimensional (3D) in vitro platforms, such as spheroids, organoids, and organ-on-chip systems, have improved physiological relevance; however, they often lack the spatial control, reproducibility, and integrative capacity needed to capture the full complexity of the TME. This review posits that the unique value of 3D bioprinting in cancer research lies in its ability to reproducibly integrate the multicomponent complexity of the TME within a controllable spatial framework, a capability that no existing 3D model can provide simultaneously. We outline the technical foundation for TME reconstruction by 3D bioprinting, which encompasses bioink design, printing strategies, and the construction of complex tumor models. We subsequently summarize its applications in tumor biology, drug screening, personalized therapy and preclinical evaluation, and discuss translational challenges, interdisciplinary integration and future research directions. This review is intended to advance both basic cancer research and precision oncology.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Base Editors for Engineering Industrial Microorganisms: Types, Applications, and Future Perspectives 基础编辑工程工业微生物：类型，应用，和未来的前景。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70266

Xurui Li, Shimin Wu, Pingfang Tian

{"title":"Base Editors for Engineering Industrial Microorganisms: Types, Applications, and Future Perspectives","authors":"Xurui Li, Shimin Wu, Pingfang Tian","doi":"10.1002/biot.70266","DOIUrl":"10.1002/biot.70266","url":null,"abstract":"<div>\u0000 \u0000 <p>Base editing encompasses technologies that enable the direct conversion of one nucleotide base into another, typically by employing deaminases fused to programmable DNA- or RNA-binding scaffolds such as CRISPR-dCas9/nCas9. Deaminase-free editing strategies are also emerging as promising alternatives. Unlike conventional CRISPR-Cas9 systems that rely on DNA double-strand breaks (DSBs) and subsequent homology-directed repair or non-homologous end joining (NHEJ), base editors operate independently of these pathways, thus enabling continuous in vivo genome evolution and phenotypic diversification. While previous reviews have summarized base editing in plants and animals, the present review focuses specifically on base editors tailored for industrial microorganisms. We provide a comprehensive overview of deaminase-dependent and glycosylase-dependent base editors, emphasizing their applications in sculpting microbial genomes, redirecting metabolic flux, and enhancing stress tolerance. In addition, we summarize recent advances in in situ bacterial base editing, an emerging frontier for industrial strain improvement. Finally, we dissect the current limitations of these tools and propose actionable strategies to enhance editing performance and broaden their applicability. By integrating these perspectives, this review aims to guide future development and deployment of base editing technologies in both model and non-model industrial microorganisms, ultimately advancing their roles in biomanufacturing, biomonitoring, and beyond.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Osmolality-Independent Impact of Sodium on Glycosylation of an Fc-Fusion Protein and the Hexosamine Biosynthesis Pathway in a Chinese Hamster Ovary Cell Line 钠对中国仓鼠卵巢细胞系fc融合蛋白糖基化和己糖胺生物合成途径的影响

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70261

Jason Reiniger, Adrian Pöttner, Lara Rosenberger, Aline Zimmer

{"title":"Osmolality-Independent Impact of Sodium on Glycosylation of an Fc-Fusion Protein and the Hexosamine Biosynthesis Pathway in a Chinese Hamster Ovary Cell Line","authors":"Jason Reiniger, Adrian Pöttner, Lara Rosenberger, Aline Zimmer","doi":"10.1002/biot.70261","DOIUrl":"10.1002/biot.70261","url":null,"abstract":"<p>This study investigates the osmolality-independent effects of sodium and potassium on the glycosylation of an Fc-fusion protein and the activity of the hexosamine biosynthesis pathway in a Chinese Hamster Ovary cell line. Previous research linked low molecular weight proteoforms of this Fc-fusion protein to reduced <i>N</i>-glycan complexity and <i>O</i>-glycan site occupancy. Through a series of batch experiments, we demonstrated that increased concentrations of sodium or potassium ions led to a reduction of these proteoforms. Our findings suggest that ion availability impacts the activity of the hexosamine biosynthesis pathway, thereby enhancing the availability of uridine diphosphate <i>N</i>-acetylglucosamine, which is a crucial substrate for glycosylation. Notably, these changes in nucleotide sugar concentration were independent of the increased osmolality. Through supplementation of intermediates that are funneled into the hexosamine biosynthesis pathway, a link between Fc-fusion protein quality and activated sugar availability was established as each supplement that elevated nucleotide sugar concentrations reduced low molecular weight proteoforms. We hypothesize that changes in sodium and potassium concentrations lead to increased uptake of nutrients and calcium, influencing metabolic pathways and enzyme activity. Altogether, this work highlights the importance of ion balance in cell culture media development for optimizing correct glycosylation during therapeutic protein production.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262501","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}

引用次数: 0

Severe Restriction of Glucose Import Enhances Recombinant Protein Production in Escherichia coli 严格限制葡萄糖进口可提高大肠杆菌重组蛋白的产量。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70268

Juan Carlos Fragoso-Jiménez, Juan Carlos Sigala, Frank Delvigne, Alfredo Martínez, Alvaro R. Lara, Guillermo Gosset

{"title":"Severe Restriction of Glucose Import Enhances Recombinant Protein Production in Escherichia coli","authors":"Juan Carlos Fragoso-Jiménez, Juan Carlos Sigala, Frank Delvigne, Alfredo Martínez, Alvaro R. Lara, Guillermo Gosset","doi":"10.1002/biot.70268","DOIUrl":"10.1002/biot.70268","url":null,"abstract":"<p>Glucose uptake through the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) enables rapid growth of <i>Escherichia coli</i> but promotes overflow metabolism that limits recombinant protein production. To define how glucose transport capacity shapes cellular physiology and bioprocess performance, we compared wild-type W3110 with two PTS-deficient derivatives, VH33 (Δ<i>ptsHIcrr</i>, constitutive <i>galP</i> expression) and WHIC (Δ<i>ptsHIcrr</i> Δ<i>mglABC</i>), in controlled stirred-tank bioreactors containing 20 g L<sup>−</sup><sup>1</sup> glucose. PTS inactivation reduced specific growth and glucose uptake rates by up to 63% and decreased acetate accumulation by more than 95%, while final biomass concentrations remained comparable. Transcriptomic analysis revealed metabolic rewiring in the PTS<sup>−</sup> strains, which displayed highly similar global transcriptional profiles. However, the upregulation of alternative carbon metabolism and fimbrial genes in VH33 indicates subtle regulatory differences that may result in differential allocation of cellular resources. When expressing GFP, VH33, and WHIC achieved 2.5- and 4.4-fold higher titers than W3110, respectively, with WHIC exhibiting the highest biomass-specific yield (37.5 mg g<sup>−</sup><sup>1</sup>). Flow cytometry demonstrated strain-dependent population heterogeneity and enrichment of recombinant protein in filamentous cells. Across strains, GFP synthesis rates approached growth dilution rates, indicating sustained intracellular accumulation. These results demonstrate that severe restriction of glucose import improves recombinant protein production by reshaping metabolic and physiological states.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262496","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}

引用次数: 0

Attenuation of Triple Selection Markers to Enhance mAb Expression in Tyrosine-Based Selection Systems via an Inducible CRISPRi Platform 通过诱导型CRISPRi平台衰减三重选择标记以增强酪氨酸选择系统中单克隆抗体的表达

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70265

Lei Cao, Liang Zhao, Yan Zhou, Qian Ye, Wen-Song Tan

{"title":"Attenuation of Triple Selection Markers to Enhance mAb Expression in Tyrosine-Based Selection Systems via an Inducible CRISPRi Platform","authors":"Lei Cao, Liang Zhao, Yan Zhou, Qian Ye, Wen-Song Tan","doi":"10.1002/biot.70265","DOIUrl":"10.1002/biot.70265","url":null,"abstract":"<div>\u0000 \u0000 <p>Chinese hamster ovary (CHO) cells are the predominant host for monoclonal antibody (mAb) production, where the choice of selection system is critical. While metabolic selection systems are favored over antibiotic-based ones to avoid purification and safety issues, traditional single-marker systems poorly regulate the light-to-heavy chain (LC/HC) ratio, which is key for yield. Although novel multi-marker systems can address this, they often lack strategies to enhance expression. To overcome these limitations, our study employed a triple-marker system based on the tyrosine biosynthetic pathway to regulate the LC/HC ratio and eliminate the need for alkaline concentrated tyrosine feeding. Furthermore, we introduced an inducible CRISPR interference (iCRISPRi) platform, which integrates SV40 promoter-targeting CRISPRi with a Tet-on system, to enhance its efficiency. This strategy upregulated three fluorescent reporter genes, resulting in a selected mini-pool with 84.84% higher cell-specific productivity and 87.50% higher final titer in tyrosine-free perfusion culture. Mechanistically, doxycycline (Dox)-induced dCas9 expression inhibited the transcription of SV40-driven markers, enriching cells with high marker integration under tyrosine deprivation and consequently increasing HC and LC gene copy numbers to boost mAb yields. This iCRISPRi strategy serves as a potential enhancer for SV40 promoter-driven systems, offering novel insights for optimizing metabolic selection.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adeno-Associated Virus Vector Mediated Gene Therapy: A Promising Approach to Transform Hypertrophic Cardiomyopathy Treatment 腺相关病毒载体介导的基因治疗：一种转化肥厚性心肌病治疗的有希望的方法。

IF 3.7 3区生物学

Biotechnology Journal Pub Date : 2026-06-17 DOI: 10.1002/biot.70262

Saif Siddiqui, Siddhi Bagwe Parab, Lokesh Kumar Bhatt

{"title":"Adeno-Associated Virus Vector Mediated Gene Therapy: A Promising Approach to Transform Hypertrophic Cardiomyopathy Treatment","authors":"Saif Siddiqui, Siddhi Bagwe Parab, Lokesh Kumar Bhatt","doi":"10.1002/biot.70262","DOIUrl":"10.1002/biot.70262","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous myocardial disease that usually arises from mutations in key sarcomeric proteins, particularly MYBPC3 and MYH7. Current pharmacological treatments, such as myosin inhibitors, calcium channel blockers, and β-blockers, reduce symptoms but do not address the underlying genetic cause of the illness. Gene therapy has emerged as a promising strategy to address HCM. Adeno-associated virus (AAV) vectors, particularly serotype AAV9, demonstrate strong cardiac tropism, long-term expression, and favorable safety, making them ideal for cardiac gene delivery. AAV-mediated gene therapy has the potential to represent paradigm shift in HCM treatment, transitioning from symptomatic management to curative interventions. However, challenges such as long-term safety, vector immunogenicity, treatment durability, and scalable manufacturing must be addressed before it can be widely adopted in routine clinical practice. The present review explores the potential of AAV-mediated gene therapy in the treatment of hypertrophic cardiomyopathy. The review discusses AAV vectors, focusing on capsid structure, their genome organization, and cardiotropic serotypes optimized for cardiovascular gene delivery. The article explores how different AAV serotypes, particularly AAV9, transduce cardiomyocytes and achieve efficient, selective cardiac tropism. Furthermore, the article discusses AAV-based therapeutic strategies for cardiomyopathy, preclinical findings, and emerging clinical trials of AAV9-mediated gene therapy.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems 利用深度学习模型在CRISPR系统中进行向导RNA优化和脱靶预测。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-06-09 DOI: 10.1002/biot.70255

Muhammad Saeed, Muhammad Arham, Imran Zafar, Adil Jamal, Majid Hussian, Muhammad Usman, Fayez Saeed Bahwerth, Muhammad Noman, Md. Belal Hossain

{"title":"Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems","authors":"Muhammad Saeed, Muhammad Arham, Imran Zafar, Adil Jamal, Majid Hussian, Muhammad Usman, Fayez Saeed Bahwerth, Muhammad Noman, Md. Belal Hossain","doi":"10.1002/biot.70255","DOIUrl":"10.1002/biot.70255","url":null,"abstract":"<div>\u0000 \u0000 <p>CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based genome and transcriptome editing technologies have emerged as powerful tools for therapeutic, agricultural, and industrial applications. However, their broader clinical and translational use remains limited by variable guide RNA (gRNA) or single-guide RNA (sgRNA) efficiency and unintended off-target activity, which may lead to genotoxic effects and major safety concerns. To address these challenges, recent research has increasingly shifted from heuristic scoring approaches and traditional machine learning (ML) methods toward deep learning (DL) models capable of learning complex sequence–function relationships from large-scale experimental datasets generated by assays such as GUIDE-seq (Genome-wide Unbiased Identification of Double-stranded Breaks Enabled by Sequencing), CIRCLE-seq (Circularization for In Vitro Reporting of Cleavage Effects by Sequencing), and CHANGE-seq (Cumulative and Homology-independent Analysis of Nuclease Genome-wide Effects by Sequencing). This review critically examines recent advances in DL approaches for gRNA optimization and off-target prediction in CRISPR systems. We discuss the development of convolutional neural networks (CNNs), recurrent neural networks (RNNs), transformer-based architectures, and foundation models designed to improve prediction accuracy, specificity, and generalizability across diverse biological contexts.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0