Targets, Volume 3, Issue 4 (December 2025) – 3 articles

Extracellular Vesicle-associated microRNAs (EV-miRNAs) are emerging as pivotal regulators of corneal health and disease, holding exceptional promise for transforming both diagnostics and therapeutics. These vesicles carry distinct miRNA signatures in biofluids such as tears, offering a powerful, non-invasive approach for early detection, risk stratification, and dynamic monitoring of corneal disorders. In addition, EV-miRNAs act as key mediators of critical biological processes, including inflammation, fibrosis, and tissue repair. Consequently, they represent attractive therapeutic targets; for example, engineered EVs loaded with miRNA mimics or inhibitors can precisely modulate these pathways to promote regeneration and suppress disease progression. Yet, despite this considerable promise, the translation of EV-miRNA research into clinical practice remains constrained by several challenges. Topmost among these are the lack of standardized EV isolation methods, variability in miRNA quantification, and the pressing need for regulatory frameworks tailored to the complexity of these biological therapeutics. Addressing these barriers is essential to ensure reproducibility, scalability, and safety in clinical applications. Accordingly, this review synthesizes current knowledge on EV-miRNA profiles in corneal diseases, critically evaluates their diagnostic and therapeutic potential, and highlights strategies to overcome existing technical and regulatory limitations. Ultimately, the successful integration of EV-miRNA-based approaches into personalized medicine frameworks could revolutionize the management of corneal diseases and substantially improve patient outcomes. Full article

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. This review explains the connections between the genesis and progression of GBM and particular cellular tumorigenic mechanisms, such as angiogenesis, invasion, migration, growth factor overexpression, genetic instability, and apoptotic disorders, as well as possible therapeutic targets that help predict the course of the disease. Glioblastoma multiforme (GBM) diagnosis relies heavily on histopathological features, molecular markers, extracellular vesicles, neuroimaging, and biofluid-based glial tumor identification. In order to improve miRNA stability and stop the proliferation of cancer cells, nanoparticles, magnetic nanoparticles, contrast agents, gold nanoparticles, and nanoprobes are being created for use in cancer treatments, neuroimaging, and biopsy. Targeted nanoparticles can boost the strength of an MRI signal by about 28–50% when compared to healthy tissue or controls in a preclinical model like mouse lymph node metastasis. Combining the investigation of CNAs and noncoding RNAs with deep learning-driven global profiling of genes, proteins, RNAs, miRNAs, and metabolites presents exciting opportunities for creating new diagnostic markers for malignancies of the central nervous system. Artificial intelligence (AI) advances precision medicine and cancer treatment by enabling the real-time analysis of complex biological and clinical data through wearable sensors and nanosensors; optimizing drug dosages, nanomaterial design, and treatment plans; and accelerating the development of nanomedicine through high-throughput testing and predictive modeling. Full article

Proteolysis-targeting chimeras (PROTACs) are a transformative therapeutic modality that co-opts the ubiquitin-proteasome system for selective protein degradation. To date, the development of PROTACs has been overwhelmingly dominated by the recruitment of four canonical E3 ligases: CRBN, VHL, MDM2, and IAP. This limited repertoire represents a critical bottleneck, restricting the scope of degradable proteins and potential therapeutic applications. Addressing this challenge, recent years have witnessed a surge in the successful recruitment of novel E3 ligases. This review provides a dedicated and comprehensive summary of this progress, focusing exclusively on the emerging E3 ligases and their cognate ligands reported for PROTAC technology outside of the well-established quartet. We detail their discovery and strategic application, highlighting how this rapidly expanding toolbox promises to overcome existing limitations and unlock the full potential of targeted protein degradation. Full article