Extracellular vesicles (EVs) have emerged as critical mediators in various disease mechanisms, particularly in cardiovascular and metabolic disorders. For instance, the study by Ohayon-Steckel highlights the role of miR-499 in platelet-derived EVs, demonstrating that its deficiency leads to impaired inflammatory cell generation and cardiac remodeling post-myocardial infarction (MI). The authors utilized RNA sequencing and luciferase assays to elucidate the interaction between miR-499 and lactoferrin, revealing that miR-499 downregulates lactoferrin expression, which is pivotal for myelopoiesis and inflammation (ref: Ohayon-Steckel doi.org/10.1161/CIRCULATIONAHA.124.073527/). Additionally, the research by Li indicates that circulating EVs from chronic kidney disease (CKD) patients exhibit cardiotoxic effects, significantly inducing apoptosis in cardiomyocytes, thus linking kidney dysfunction to cardiac complications (ref: Li doi.org/10.1161/CIRCULATIONAHA.125.075579/). These findings underscore the dual role of EVs in both promoting and mitigating disease processes, suggesting their potential as therapeutic targets or biomarkers in cardiovascular diseases. Moreover, the investigation into cyclic Cushing's syndrome by Nowak reveals the complexities of cortisol secretion patterns and their implications for patient outcomes. This retrospective study across multiple endocrine centers identified key clinical challenges associated with diagnosing and managing cyclic Cushing's syndrome, emphasizing the need for improved diagnostic strategies (ref: Nowak doi.org/10.1016/S2213-8587(25)00249-9/). The interplay between EVs and metabolic dysregulation is further illustrated by the findings of Wang, who demonstrated that phosphorylation of lactate dehydrogenase A (LDHA) is crucial for the release of EV-derived circSEPT9, which enhances chemoresistance in triple-negative breast cancer cells (ref: Wang doi.org/10.1016/j.drup.2025.101324/). Collectively, these studies highlight the multifaceted roles of EVs in disease mechanisms, providing insights into their potential as both biomarkers and therapeutic targets.

The therapeutic potential of extracellular vesicles (EVs) is being increasingly recognized, particularly in gene delivery and immunotherapy. Elsharkasy's study presents a modular strategy for EV-mediated CRISPR-Cas9 delivery, utilizing aptamer-based loading and UV-activated cargo release to enhance the efficiency of gene editing (ref: Elsharkasy doi.org/10.1038/s41467-025-65995-3/). This innovative approach addresses the significant challenge of intracellular delivery of the Cas9 ribonucleoprotein complex, which is crucial for effective gene therapy. Furthermore, Ma's research on exosome-mediated delivery of CRISPR-Cas12a for HIV-1 proviral DNA editing demonstrates the feasibility of using engineered exosomes to target CD4+ T cells, thereby overcoming barriers associated with traditional gene therapy methods (ref: Ma doi.org/10.1016/j.ymthe.2025.11.012/). In addition to gene therapy, the application of EVs in plant protection against fungal pathogens is explored by Niño-Sánchez, who engineered soil bacteria to produce double-stranded RNAs targeting fungal genes, showcasing a novel cross-kingdom RNA trafficking mechanism (ref: Niño-Sánchez doi.org/10.1016/j.molp.2025.11.003/). This study highlights the versatility of EVs in delivering therapeutic agents across species, potentially revolutionizing agricultural practices. Moreover, Crescitelli emphasizes the importance of studying solid tissue-derived EVs (ST-EVs) to gain insights into tissue-specific molecular dynamics, which could lead to advancements in understanding disease mechanisms and developing targeted therapies (ref: Crescitelli doi.org/10.1002/jev2.70185/). These findings collectively illustrate the transformative potential of EVs in therapeutic applications, paving the way for innovative strategies in gene therapy and disease management.

Extracellular vesicles (EVs) play a pivotal role in cancer biology, particularly in tumor progression and therapeutic resistance. Wang's study highlights the significance of LDHA phosphorylation in the release of EV-derived circSEPT9, which enhances chemoresistance in triple-negative breast cancer cells through modulation of the miR-515-5p/KIAA1429 axis (ref: Wang doi.org/10.1016/j.drup.2025.101324/). This research underscores the intricate mechanisms by which EVs facilitate intercellular communication and contribute to therapeutic challenges in cancer treatment. Additionally, Li's investigation into breast cancer-secreted DPP3 reveals its role in promoting lung metastasis by remodeling the vascular niche via the Rap1 signaling pathway, further illustrating the importance of EVs in metastasis (ref: Li doi.org/10.1002/jev2.70182/). Moreover, Zhang's work identifies CKAP4 as a non-invasive diagnostic biomarker for diabetic nephropathy, emphasizing the potential of EVs in providing insights into cancer-related metabolic disorders (ref: Zhang doi.org/10.1002/jev2.70208/). The study by Shen on engineered bacterial biomimetic vesicles for vaccine delivery also highlights the innovative use of EVs in immunotherapy, showcasing their potential to enhance vaccine efficacy (ref: Shen doi.org/10.1002/jev2.70207/). Collectively, these studies illustrate the multifaceted roles of EVs in cancer research, from facilitating metastasis to serving as diagnostic tools and therapeutic carriers, thereby opening new avenues for cancer treatment and management.

Extracellular vesicles (EVs) are increasingly recognized as key regulators in metabolic disorders, particularly in obesity and diabetes. Wang's research demonstrates that adipocyte-derived EVs play a crucial role in central leptin sensitivity and energy homeostasis, revealing that engineered EVs modified with specific membrane proteins can reverse leptin resistance in obese mice (ref: Wang doi.org/10.1016/j.cmet.2025.10.005/). This finding highlights the potential of EVs as therapeutic agents in combating obesity-related metabolic dysregulation. Additionally, Long's study on subcutaneous white adipose tissue-derived EVs indicates their role in maintaining intestinal homeostasis, particularly in aging mice, suggesting a complex interplay between adipose tissue and gut health (ref: Long doi.org/10.1172/JCI188947/). Furthermore, the investigation by Li into the cardiotoxic effects of circulating EVs from CKD patients underscores the link between metabolic disorders and cardiovascular health, revealing that these EVs can induce apoptosis in cardiomyocytes (ref: Li doi.org/10.1161/CIRCULATIONAHA.125.075579/). The study by Crescitelli emphasizes the importance of solid tissue-derived EVs in understanding metabolic dynamics, providing insights into their potential as biomarkers for metabolic disorders (ref: Crescitelli doi.org/10.1002/jev2.70185/). Collectively, these studies illustrate the multifaceted roles of EVs in metabolic disorders, highlighting their potential as both therapeutic targets and biomarkers in the management of obesity and related conditions.

Extracellular vesicles (EVs) are emerging as critical players in neurobiology, particularly in the context of neurodegenerative diseases and synaptic function. Jank's study characterizes EVs derived from multiple sclerosis (MS) white matter, revealing dysregulation in synaptic, mitochondrial, and aging-related pathways (ref: Jank doi.org/10.1002/jev2.70197/). This research highlights the potential of EVs as biomarkers for MS and their role in mediating neuroinflammation and neurodegeneration. Additionally, Ray's investigation into HIV-associated neurocognitive disorders (HAND) demonstrates that astrocyte-derived EVs carrying HIF-1α-targeting siRNA can alleviate Alzheimer's-like pathology in humanized mice, suggesting a novel therapeutic approach for neurodegenerative conditions associated with HIV (ref: Ray doi.org/10.1002/jev2.70191/). Moreover, the study by Zhao identifies outer membrane vesicles (OMVs) as vehicles for antibiotic resistance gene transfer in Campylobacter, underscoring the role of EVs in microbial interactions and their implications for neurobiology (ref: Zhao doi.org/10.1002/jev2.70195/). These findings collectively illustrate the diverse functions of EVs in neurobiology, from serving as biomarkers for disease progression to facilitating therapeutic interventions, thereby enhancing our understanding of their role in brain health and disease.

Extracellular vesicles (EVs) are integral to the immune system, serving as mediators of intercellular communication and immune responses. Grenier-Pleau's study emphasizes the role of EVs in defining discrete nano-based niches within the human hematopoietic system, highlighting their importance in maintaining hematopoietic stem cell (HSC) niches and orchestrating immune cell development (ref: Grenier-Pleau doi.org/10.1002/jev2.70181/). This research underscores the complexity of EV-mediated signaling in the immune microenvironment and its implications for hematopoiesis. Additionally, Zhang's identification of CKAP4 as a non-invasive biomarker for diabetic nephropathy demonstrates the potential of EVs in diagnosing metabolic disorders that have immunological implications (ref: Zhang doi.org/10.1002/jev2.70208/). Moreover, the study by Kawai-Harada introduces a novel molecular screening platform for selecting proteins that direct EVs to specific tissues, enhancing the specificity of therapeutic delivery (ref: Kawai-Harada doi.org/10.1002/jev2.70184/). This innovative approach could revolutionize targeted immunotherapies by improving the delivery of therapeutic agents to desired sites. Collectively, these studies highlight the multifaceted roles of EVs in immunology, from facilitating immune cell interactions to serving as diagnostic tools, thereby opening new avenues for therapeutic interventions in immune-related disorders.

Extracellular vesicles (EVs) are gaining traction as promising vehicles for gene therapy, offering innovative solutions to overcome traditional delivery challenges. Elsharkasy's study presents a modular strategy for EV-mediated CRISPR-Cas9 delivery, utilizing aptamer-based loading and UV-activated cargo release to enhance gene editing efficiency (ref: Elsharkasy doi.org/10.1038/s41467-025-65995-3/). This approach addresses the critical hurdle of intracellular delivery of the Cas9 ribonucleoprotein complex, showcasing the potential of EVs in advancing gene therapy applications. Furthermore, Ma's research on exosome-mediated delivery of CRISPR-Cas12a for HIV-1 proviral DNA editing demonstrates the feasibility of using engineered exosomes to target CD4+ T cells, thereby enhancing the specificity and efficacy of gene editing in therapeutic contexts (ref: Ma doi.org/10.1016/j.ymthe.2025.11.012/). Additionally, Niño-Sánchez's investigation into cross-kingdom RNA trafficking highlights the potential of EVs in delivering RNA-based therapeutics for plant protection against fungal pathogens, showcasing their versatility beyond mammalian systems (ref: Niño-Sánchez doi.org/10.1016/j.molp.2025.11.003/). The study by Yan on scalable production of EV-encapsulated AAVs for familial hypercholesterolemia therapy further emphasizes the practical applications of EVs in gene therapy, achieving significant improvements in production efficiency (ref: Yan doi.org/10.1002/jev2.70186/). Collectively, these studies illustrate the transformative potential of EVs in gene therapy, paving the way for innovative strategies to enhance therapeutic efficacy and specificity.