Next-Generation Nucleic Acid Delivery: From Nanocarrier Design to AI-Guided Optimization

Nucleic acid delivery is a rapidly evolving field that bridges nanotechnology, molecular biology, and computational science to enhance the therapeutic potential of genetic materials. Platforms enabling the controlled and efficient delivery of mRNA, siRNA, and genome-editing components, among others, have become central to therapeutic innovation, with lipid nanoparticles demonstrating early clinical success in vaccine development and gene therapy. Despite this progress, significant challenges remain in achieving precise biodistribution, overcoming biological barriers, and minimizing off-target effects. Advances in engineered nanocarriers, stimuli-responsive systems, and polymeric biomaterials, including cyclodextrin- and dextrin-based architectures, are expanding the design space, while AI-driven formulation approaches are accelerating optimization and opening new routes toward targeted, personalized medicine.This Research Topic aims to advance the understanding and development of next-generation nucleic acid delivery technologies by bringing together interdisciplinary perspectives on the design, characterization, and optimization of delivery systems that enhance pharmacological performance and therapeutic precision. The central focus is on structure–function relationships that govern delivery efficiency, cellular uptake, and targeting accuracy, including lipid nanoparticles, polymer-based platforms, stimuli-responsive architectures, and hybrid nanocarrier systems. We seek both experimental and computational contributions that clarify how composition, structural properties, and biointeractions collectively determine biological performance.The scope of this Research Topic will focus on the design, engineering, and optimization of nucleic acid delivery systems and their translation toward safer and more effective therapeutics. To gather further insights in this area, we welcome articles addressing, but not limited to, the following themes:- Design and engineering of lipid nanoparticles, polymeric systems, and hybrid nanocarriers nucleic acid therapeutics, including mRNA, RNAi, gene-editing systems, and other emerging modalities- Stimuli-responsive and precision delivery systems for targeting and biodistribution optimization- Synthetic design and structural/biological characterization of polymer-based biomaterials with tunable architecture and controlled release- Pharmacokinetics, immunogenicity, and safety profiles of nucleic acid therapeutics- Structure–property–function relationships governing delivery efficiency, stability, and biointeractions- Computational and AI-assisted approaches to formulation design and system optimization- Translational challenges and clinical perspectives for next-generation nucleic acid delivery platforms Topic editors: Gjylije Hoti, Satheesh Ellipilli Source: https://www.frontiersin.org/research-topics/82250/next-generation-nucleic-acid-delivery-from-nanocarrier-design-to-ai-guided-optimization