DNA has been widely employed as a building block for the construction of sophisticated nanostructures with pre-designed sizes and shapes by complementary base pairing. With outstanding programmability, addressability, and biocompatibility, DNA nanostructures have been further developed as nanocarriers for drug delivery in biomedical researches. Noticeably, DNA nanocarriers can be rationally designed for loading and delivering nucleic acid drugs based on their inherent homology. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas9) ribonucleoprotein-based gene editing system has also been efficiently delivered by DNA nanocarriers. In this review, we will summarize the recent progress in the design of versatile DNA nanocarriers, such as rolling circle amplification (RCA)-based DNA nanostructure, branched DNA, and DNA origami, for delivery of single-guide RNA (sgRNA)/Cas9 ribonucleoprotein. Furthermore, the challenges and future opportunities of DNA nanotechnology in the delivery of gene editing system will be discussed.

Nucleic acid nanotechnology has been developed to be a promising strategy to construct various nano-biomaterials with structural programmability, spatial addressability, and excellent biocompatibility. Self-assembled nucleic acid nanostructures have been employed in a variety of biomedical applications, such as bio-imaging, diagnosis, and therapeutics. In this manuscript, we will review recent progress in the development of multifunctional nucleic acid nanostructures as gene drug delivery vehicles. Therapeutic systems based on RNA interference (RNAi), clustered regularly interspaced short palindromic repeat associated proteins 9 system (CRISPR/Cas9) genome editing, gene expression, and CpG-based immunostimulation will be highlighted. We will also discuss the challenges and future directions of nucleic acid nanotechnology in biomedical research.