Smart micro/nanoneedles for gene delivery

Gene therapy, a transformative field in biomedicine, holds immense promise for treating a wide range of diseases. Smart micro/nanoneedles (MNs/NNs) emerged as non-viral carriers, offering safety and reduced immunogenicity, in addition to precise and controlled gene delivery, and represent promising platforms for gene delivery. They can also be tailored to respond to specific biological or environmental triggers, enabling precise targeting and localized delivery, ensuring that therapeutic genes reach their intended destination. Despite significant progress, challenges persist in scalable manufacturing, biocompatibility and safety, and genetic cargo stability. The incorporation of artificial intelligence (AI) into design and predictive modelling offers promising and cost-effective solutions to these limitations. This review provides a comprehensive analysis of MN/NN fabrication methodologies that enable structural and functional customization, while highlighting the interdisciplinary nature of MN/NN technologies and their transformative role in the future of gene therapy.