DNA Nanostructures-based Delivery of RNA Drugs for Cancer Therapy

Abstract

The emergence of RNA therapeutics, including antisense oligonucleotides, small interfering RNA, microRNA, messenger RNA and CRISPR-based systems, has revolutionized targeted cancer treatment by enabling precise gene regulation. However, their clinical translation is significantly hampered by inherent instability, inefficient cellular uptake, and potential immunogenicity. DNA-based nanostructures have recently emerged as highly programmable and biocompatible platforms for the efficient delivery of RNA therapeutics. This review comprehensively summarizes the recent advancements in DNA nanostructure-based delivery systems (e.g., DNA origami, tetrahedral frameworks) for RNA drugs, with a specific focus on cancer applications. We highlight the fundamental design principles of various DNA nanostructures and examine strategies for efficiently loading RNA payloads and achieving controlled, stimuli-responsive release (e.g., pH, ATP, enzymes) within the tumor microenvironment. The applications of these delivery systems in cancer gene therapy, immunotherapy, and combination regimens are extensively discussed. Finally, we address current challenges and future perspectives in the clinical translation of RNA drug delivery systems based on DNA nanostructures, emphasizing the need for improved stability, targeting specificity, and scalable preparation.

Keywords

DNA nanotechnology / RNA therapeutics / Drug delivery system / Nanostructure / Cancer therapy

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