Progress and applications of microneedle-based gene therapy

: Gene therapy holds considerable promise for treating a wide range of intractable diseases through the modification of specific genes. However, gene therapeutics such as plasmid DNA, messenger RNA, and CRISPR-based systems are susceptible to degradation, face challenges in crossing cellular barriers, and may induce immune-related adverse effects, thereby limiting their clinical translation. Microneedles create microchannels that penetrate tissue barriers and, when combined with various carrier materials, enhance nucleic acid stability and intracellular delivery efficiency. This review summarizes the compatibility of different microneedle configurations with gene-delivery vectors, compares the effects of various fabrication processes on the activity of therapeutic agents, and elucidates the mechanisms underlying barrier penetration and delivery by microneedles. Recent advances in the application of microneedle-based gene therapy in dermatology, oncology, and nucleic acid vaccination are also discussed. Finally, current challenges, including drug loading, mass production, and safety evaluation, are analyzed, and the prospects for smart, responsive, and integrated diagnostic and therapeutic microneedles are highlighted.