DNA therapy faces multiple challenges during clinical translation. These challenges include the poor DNA stability, low DNA transfection efficiency, inefficient genomic integration, and inadequate delivery of therapeutic DNA. To address these challenges, this review focuses on non-viral vector systems that can improve the targeted delivery and therapeutic effect of DNA drugs, and provides a systematic review of the latest research developments in this field. This review starts with an analysis of the core challenges in DNA delivery. Taking the key challenges in DNA drug delivery as its starting point, this paper provides a detailed overview of the characteristics, applications and research findings of various non-viral carriers, including lipid carriers, polymeric carriers, inorganic materials, peptide-based carriers and glyconanoparticle. It further analyses the practical bottlenecks and developmental obstacles faced by non-viral carriers in clinical translation, thereby offering guidance for the future development of the field of DNA therapy.

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