{"title":"Immuno-Engineering in the AI Era: From Fundamental Research to Clinical Translation","authors":"Meng Zhu, Andy Tay, Xianlei Li","doi":"10.1002/adtp.202500087","DOIUrl":"10.1002/adtp.202500087","url":null,"abstract":"<p>Artificial intelligence (AI) plays a pivotal role in advancing immune engineering, a field aimed at developing personalized therapies for cancer, autoimmune diseases, and infections. AI is overcoming significant challenges in immune engineering, such as immune system complexity, patient-specific variability, and the dynamic interactions within the immune microenvironment. This perspective highlights how AI is bridging the gap between laboratory research and clinical application through three major pillars: 1) Mechanistic Decoding, where AI integrates multi-omics data to understand immune system complexity and predict molecular interactions; 2) Therapeutic Innovation, where AI designs personalized immunotherapies, such as optimizing antibody-antigen binding and immune receptor dynamics; and 3) Clinical Acceleration, where AI enhances clinical trial designs, speeds up drug development, and adjusts therapies in real-time based on patient responses. Further discussion addresses algorithmic bias, data privacy, and the need for global standards in AI-powered decision-making, ethical and regulatory challenges. AI is not only enabling breakthroughs in immune engineering but also paving the way for customized immune-based therapies. It ensures that the technologies are applied responsibly and equitably in clinical practice.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145101006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samarendra Mohanty, Pratyajit Mohapatra, Amir Singh, William Marks, Subrata Batabyal, Michael Carlson, Najam Sharif, Sanghoon Kim
{"title":"Topology and Mechanism of Broadband and Fast Multi-Characteristic Opsin for Neuromodulation","authors":"Samarendra Mohanty, Pratyajit Mohapatra, Amir Singh, William Marks, Subrata Batabyal, Michael Carlson, Najam Sharif, Sanghoon Kim","doi":"10.1002/adtp.202500009","DOIUrl":"10.1002/adtp.202500009","url":null,"abstract":"<p>Optogenetics has enabled targeted manipulation of neural circuits, offering insights into the intricacies of brain function and paving the way for potential therapeutic applications in neurological disorders. Multi-characteristic Opsin (MCO) is an optogenetics therapy candidate that is undergoing multiple clinical trials, including randomized control trials. However, its cellular topography and mechanism of action have remained unknown. Here, we reveal the biophysical characteristics of the MCO molecule, including its unique structure and function, using a combination of predictive protein modeling, western blotting-based protease protection assay, and electrophysiology. MCO’s first extracellular subunit forms a cation-channel pore, while the second subunit is partially embedded in the membrane, extending to the third intracellular cytoplasmic subunit. Functional studies using whole-cell recordings showed that MCO is activated by broadband visible light with fast on-off kinetics with high photosensitivity, and large dynamic range across the visible spectrum, enabling best-in-class light-activation of MCO-expressing cells. Further, multi-electrode array recording confirmed multi-color light-activation of MCO-expressing neurons in the retina. The unique topological and functional activation features of fused MCO protein represent novel findings linking the in-vitro and in-vivo efficacy of this opsin, which is particularly important for neuromodulation leading to vision restoration in retinal degenerative diseases and other neurological therapies.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA-Based Therapeutics: Cutting-Edge Advances in Clinical Research","authors":"Débora Ferreira, Ligia R. Rodrigues","doi":"10.1002/adtp.202500082","DOIUrl":"10.1002/adtp.202500082","url":null,"abstract":"<p>Over the years, the relevance of gene therapy has increased as an alternative to conventional drugs. Pharmaceutical industries have been directing their efforts toward the creation of novel gene-based therapies for a broad range of diseases. RNA-based therapeutics can efficiently trigger gene silencing and, despite the initial research setbacks, this technology laid the groundwork for advancements in RNA-based drug design that ultimately contributed to the remarkably rapid advance of messenger RNA (mRNA) vaccines to combat the COVID-19 pandemic. In light of this information, RNA medicines are currently well-positioned to have a noteworthy impact in clinical practice. Various RNA medicines have received clinical approval, while others are still in the research phase or undergoing preclinical trials. In this review, an overview of RNA-based therapeutics is aimed to provide, including antisense oligonucleotides and RNA interference-based mechanisms, mRNA-encoded approaches, aptamers, and clustered regularly interspaced short palindromic repeats (CRISPR-Cas)-mediated genome editing. Furthermore, the commonly used chemistries in drug delivery systems and strategies for targeting specific cells, as well as the key nanocarriers used in RNA loading, are explored. The main advances and current challenges will be thoroughly summarized.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Wang, Manwen Yang, Hang Yin, Zhen Li, Xianwen Wang, Lei Shi
{"title":"Fungal Keratitis: Clinical Presentations, Mechanism and Management Strategies","authors":"Min Wang, Manwen Yang, Hang Yin, Zhen Li, Xianwen Wang, Lei Shi","doi":"10.1002/adtp.202500247","DOIUrl":"10.1002/adtp.202500247","url":null,"abstract":"<p>Fungal keratitis (FK) is a common cause of blindness in tropical and subtropical regions and is caused mainly by infections caused by filamentous fungi such as the Aspergillus genus. The diagnosis and recovery of FK are complex compared to other ocular diseases. Owing to the anatomy and psychological properties of the cornea, it is difficult for ocular drugs to penetrate the cornea and achieve therapeutic concentrations. In the past 20 years, the clinic has used the traditional medications natamycin, voriconazole, and amphotericin B as first-line treatments. However, the effectiveness of conventional topical antifungal drugs is limited by the cornea's barrier, tear drainage, and challenges in drug penetration and bioavailability. Therefore, novel therapies or drug delivery systems to improve the treatment of FK are urgently needed. In this review, we discuss and summarize the progress of some promising antifungal management methods.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Negar Ordouzadeh, Rossella Crescitelli, Agnes Zimmer, Petra Tjärnlund, Cecilia Lässer, Jan Lötvall, Kyong-Su Park
{"title":"Optimization of the Isolation Method for Large-Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy","authors":"Negar Ordouzadeh, Rossella Crescitelli, Agnes Zimmer, Petra Tjärnlund, Cecilia Lässer, Jan Lötvall, Kyong-Su Park","doi":"10.1002/adtp.202500084","DOIUrl":"10.1002/adtp.202500084","url":null,"abstract":"<p>Bacterial vesicles have emerged as therapeutic drug candidates to treat a wide range of diseases, including cancer. However, critical concerns remain regarding their safety, in view of inducing systemic inflammation. To address this, semi-synthetic bacterial vesicles (SyBV) have recently been developed, directly derived from bacterial cell membranes. These vesicles have reduced toxicity but retained immunomodulatory ability, which is important for immuno-oncology purposes. In this study, the manufacturing process of SyBV has been further refined to meet Good Manufacturing Practice (GMP) standards. Multiple steps are reconsidered in the optimized method, including adaptation of centrifugation steps, benzonase treatment, and elimination of sonication steps, thereby producing a new set of optimized SyBV, designated as SyBV<sup>Opti</sup>. Similarly to SyBV isolated using the previous protocol, SyBV<sup>Opti</sup> do not activate macrophages but stimulate dendritic cells to produce IL-12 in a dose-dependent manner—moreover, these vesicles attenuate tumor growth in vivo in a model of malignant melanoma. Further, the optimized process applies to a GMP-compatible <i>Escherichia coli</i> source for producing SyBV<sup>Opti</sup> under GMP conditions. Collectively, these findings describe a reliable technique for large-scale production of SyBV with preserved therapeutic potential, allowing GMP manufacturing and translation of these bioactive vesicles into clinical practice.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rewiring Neuroimmunity: Nanoplatform Innovations for CNS Disease Therapy","authors":"Muhammad Usman Akbar, Weiwei Guo, Xin Shen, Yimeng Fang, Yilin Liu, Peng-Yuan Wang, Roey Elnathan, Yaping Chen","doi":"10.1002/adtp.202500124","DOIUrl":"10.1002/adtp.202500124","url":null,"abstract":"<p>Central nervous system (CNS) diseases pose a significant global health challenge, currently affecting one in six individuals worldwide. Despite extensive research into their molecular and cellular mechanisms, effective treatment remains elusive due to the inherent complexity of CNS disorders and the protective constraints of the blood-brain barrier (BBB).Conventional monotherapies often fail to produce satisfactory outcomes. In recent years, nanomaterials have emerged as promising therapeutic platforms—offering enhanced pharmacokinetics, improved biodistribution, and reduced systemic toxicity. More importantly, multifunctional nanomaterials can be engineered to actively target the brain parenchyma and lesion sites, co-deliver multiple therapeutics, and modulate neuroimmune responses synergistically. Their tunability and adaptability to diverse pathological contexts make them well-suited to address the multifactorial nature of CNS diseases. This review discusses the mechanisms contributing to therapeutic resistance in common brain disorders and highlights the potential of engineered nanomaterials that can address the multifaceted disease microenvironment. We also identify current challenges and prospects for the rational design of multifunctional nanoplatforms tailored to CNS disease treatment.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanical Interactions Impact the Functions of Immune Cells and Their Application in Immunoengineering","authors":"Yu-Chang Chen, Nghi M. Tran, Kyle H. Vining","doi":"10.1002/adtp.202500067","DOIUrl":"10.1002/adtp.202500067","url":null,"abstract":"<p>Immune cells experience a wide range of modes and magnitudes of mechanical forces as they infiltrate tissues and physically interact with other cells. Biophysical forces influence cell phenotypes through mechanosensing of the cytoskeleton, cell adhesion, catch and slip bonds, and mechanically gated ion channels. As a result, different mechanical environments impact the function and expression of immune cell receptors, which subsequently affects local and systemic immune responses. Mechanical coupling of immune cell receptors can be exploited in immunoengineering applications such as adoptive cell transfer and artificial antigen-presenting cells through biomaterial systems with tunable mechanical properties that regulate receptor expression and cell activation. This review covers immune cell receptors in the adaptive and innate immune system that respond to mechanical forces and their potential to be applied for advancing current immunotherapies.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 9","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saira Nujoom Muhammad, Zahara T Zakariya, Sherin Shaji, Anjali K Sunilkumar, Amal George, Sreedevi P Radhakrishnan, Shantikumar V Nair, Manzoor Koyakutty
{"title":"Injectable Immune-Engineered Hydrogel Niche Remote from the Immune Suppressed Tumor Microenvironment for Cancer Immunotherapy","authors":"Saira Nujoom Muhammad, Zahara T Zakariya, Sherin Shaji, Anjali K Sunilkumar, Amal George, Sreedevi P Radhakrishnan, Shantikumar V Nair, Manzoor Koyakutty","doi":"10.1002/adtp.202500120","DOIUrl":"10.1002/adtp.202500120","url":null,"abstract":"<p>Immunocompromise is a hallmark of cancer, affecting both the peripheral immune system and local tumor microenvironment (TME). Current immunotherapies like checkpoint inhibitors, CAR-T cells, and neo-antigen vaccines show limited efficacy due to severe immunosuppression in most patients. Here, an immunologically engineered injectable immunehydrogel (iHG) is reported that can: i) recruit the desired set of immune cells away from the suppressed TME and peripheral organs, ii) activate them within a protective ambit of engineered immune-stimulatory hydrogel niche, and iii) release them to target cancer even in distant locations. Biodegradable and injectable iHG compositions are tested and optimized for their ability to attract and activate dendritic cells (DC), macrophages, monocytes, natural killer (NK) cells, B cells, and T cells via stimulator of interferon genes (STING), TLR, CD86, and Th1-polarized cytokine pathway without requiring exogenously introduced neo-antigens as vaccines. In a mouse melanoma model, optimized iHGs elicit a robust antitumor immune response through innate and adaptive arms. Most importantly, iHGs as a single agent immunomodulator exhibit better tumor control than when combined with anti-PD1 immune checkpoint antibody. These findings highlight the potential of engineering immunologically functional and injectable hydrogel niches as a new type of immunotherapeutics to reprogram immune cells to overcome both local and systemic immunosuppression and combat cancer effectively.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 7","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Candela Zorzo, Lucía Rodríguez-Fernández, Emily Gabriela Castillo-Escalona, Juan A. Martínez, Laura Mañas, Natalia Arias, Jorge L. Arias
{"title":"Automated Transcranial Photobiomodulation in Healthy Rats: Effects on Working Memory and Brain Markers","authors":"Candela Zorzo, Lucía Rodríguez-Fernández, Emily Gabriela Castillo-Escalona, Juan A. Martínez, Laura Mañas, Natalia Arias, Jorge L. Arias","doi":"10.1002/adtp.202500002","DOIUrl":"10.1002/adtp.202500002","url":null,"abstract":"<p>Photobiomodulation (PBM) uses red and near-infrared light to stimulate biological processes through cytochrome c oxidase (CCO) activation, enhancing ATP synthesis and neuroprotection. This study evaluates the PBM effects on spatial working memory (WM) and cellular mechanisms in healthy adult male rats, focusing on CCO activity, c-Fos, and synaptogenesis-related proteins. PBM (810 nm, 40 Hz, 20 J cm<sup>−2</sup>) is applied for five consecutive days (PBM-C) or five alternating days (PBM-A). PBM improves spatial WM in both groups compared to controls. CCO activity decreases in the prefrontal and retrosplenial cortex, as well as in the hippocampus, suggesting more efficient energy use during cognitive tasks. PBM increases c-Fos expression in the prefrontal and parietal cortex, reflecting heightened neuronal activity. Synapsin-I levels rise in the prefrontal cortex for both protocols, while PBM-C increases PSD-95 in the hippocampus. GFAP expression decreases in cortical regions with both protocols, while PBM-C increases it in the prefrontal cortex. These findings suggest that PBM PBM-C enhances prefrontal and hippocampal synapses, potentially underlying observed WM improvements. This study highlights the PBM potential in modulating CCO activity and synaptic plasticity, providing a basis for identifying effective schedules and targets for WM preservation and treatment.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 8","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mimicking Biochemical Traits with a Synthetic Lipid Nanoparticles SARS-COV-2 Model (Adv. Therap. 6/2025)","authors":"Ignasia Handipta Mahardika, Hyun Park, Eunjin Huh, Changyoon Baek, Shin-Gyu Cho, Kwang-Hwan Jung, Junhong Min, Kwanwoo Shin","doi":"10.1002/adtp.202570013","DOIUrl":"10.1002/adtp.202570013","url":null,"abstract":"<p>In article 2400401, Junhong Min, Kwanwoo Shin, and co-workers present a synthetic lipid nanoparticle (LNP) virus model that mimics SARS-CoV-2 by encapsulating mRNA and nucleocapsid (N) protein, with spike (S) protein on its surface. This model replicates the virus's key biochemical traits, offering a safe, scalable platform for evaluating diagnostic tools through RT-qPCR and commercial rapid antigen kits.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"8 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202570013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}