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<p>mRNA-based therapy represents a transformative paradigm for treating a broad spectrum of diseases, yet its clinical translation is limited by persistent challenges in delivery. DNA nanotechnology, with its inherent programmability and biocompatibility, offers a promising solution to this bottleneck. This review focuses on three major DNA-based nanosystems for mRNA delivery: branched DNA nanohydrogels with high cargo capacity, nucleic acid origami structures offering precise structural control, and polymer-DNA hybrid nanosystems exhibiting functional synergy. We analyze their design principles, mechanisms of mRNA encapsulation and controlled release, and evaluate their performance in biomedical applications. Finally, we discuss existing challenges and outline future directions for advancing DNA-based mRNA delivery platforms.</p>

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Engineering DNA-based nanosystems for mRNA delivery

  • 期刊论文

  • 发表日期：

    2026年7月8日

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  • Wenqi Tang,
  • Fan Xiao,
  • Dayong Yang

摘要

mRNA-based therapy represents a transformative paradigm for treating a broad spectrum of diseases, yet its clinical translation is limited by persistent challenges in delivery. DNA nanotechnology, with its inherent programmability and biocompatibility, offers a promising solution to this bottleneck. This review focuses on three major DNA-based nanosystems for mRNA delivery: branched DNA nanohydrogels with high cargo capacity, nucleic acid origami structures offering precise structural control, and polymer-DNA hybrid nanosystems exhibiting functional synergy. We analyze their design principles, mechanisms of mRNA encapsulation and controlled release, and evaluate their performance in biomedical applications. Finally, we discuss existing challenges and outline future directions for advancing DNA-based mRNA delivery platforms.