Next-generation viral vectors for gene therapy: Innovations in engineering, safety, and translational development

Viral vector gene therapy represents a rapidly advancing field at the intersection of molecular medicine, biotechnology, and clinical translation. Viral vectors, including derivatives from adenoviruses, adeno-associated viruses, and retroviruses, are powerful vehicles for delivering therapeutic genetic material to specific cells and tissues, enabling the treatment of a growing list of inherited disorders, cancers, and rare diseases. Over recent years, research has delivered a robust pipeline of engineered vectors and approved therapies, benefiting from major improvements in vector biology, capsid and cargo design, screening platforms and in silico prediction models, scalable manufacturing, and animal and organoid models. Despite these advances, true translational promise of viral vector gene therapy remains hindered by barriers such as limited target specificity and potency, pre-existing immunity, dose-dependent immune-mediated toxicities, and the disconnect between preclinical prediction and clinical outcomes. Notably, there is a need for more predictive frameworks that integrate vector design, immune profiling, and translational modeling to better anticipate clinical efficacy and safety.This Research Topic aims to showcase breakthroughs in engineering safer, more potent, and translatable viral vector platforms for gene therapy. Specifically, the goal is to deepen the scientific community’s understanding of the obstacles to clinical translation. Contributors are encouraged to present studies exploring novel vectors, rational engineering of vector components, improvements in predictive modeling of in vivo performance, and new strategies to bridge the gap between preclinical and clinical evaluation. By encouraging cross-disciplinary contributions, this initiative seeks to define the state of the art in addressing the critical safety, efficiency, and scalability challenges facing next-generation viral vector gene therapies.This Research Topic will consider original research and authoritative reviews that advance the design, evaluation, and application of viral vectors for gene therapy. Coverage is limited to studies focusing on translational challenges and technological advancements in vector development, rather than broad basic virology or unrelated delivery systems. To foster comprehensive discussion, we welcome articles addressing, but not limited to, the following themes:o Development and characterization of novel viral vectors, including platforms based on engineered or unconventional viruses and chimeric constructso Capsid and cargo engineering to optimize targeting, detargeting, and immune evasiono Use and optimization of animal, ex vivo, and organoid models to predict vector performance, biodistribution, and toxicologyo Strategies to evade intrinsic cellular antiviral responses and restriction factorso Novel techniques and assays to characterize and predict clinical translation, including single-cell analysis and in silico modelingo Approaches to overcome immune-related toxicities, improve dose optimization, and enhance scalability and stability in vector manufacturingAppendix: We invite both original research articles and comprehensive review papers that fall within these thematic areas. Topic editors: Estrella Lopez Gordo, ALBERTO MOLINA GIL, Irene Sanchez-Martin Source: https://www.frontiersin.org/research-topics/79270/next-generation-viral-vectors-for-gene-therapy-innovations-in-engineering-safety-and-translational-development