Tetrahedral DNA Nanostructure-Delivered DNAzyme for Gene Silencing to Suppress Cell Growth

DNAzymes are synthetic oligonucleotides that are capable of cleavaging target mRNA to exert gene-silencing activity and are considered as promising therapeutic agents. Dz13 is a DNAzyme that cleaves the mRNA of c-Jun and suppresses the growth of squamous cell carcinomas. However, DNAzymes exhibit low cellular uptake efficacy and require a suitable drug delivery system. In this study, we directly added the Dz13 sequence to the 5'-end of single-stranded DNA to form modified tetrahedral DNA nanostructures (TDN-Dz13). The TDNs were used to deliver the single-stranded DNAzyme Dz13 into cells. Dz13 delivered by the TDNs showed high cellular uptake efficiency and still maintained intracellular gene-silencing activity to cleave the target c-Jun mRNA, which reduced cell proliferation. This study may help find a convenient approach for the delivery of DNAzymes to regulate target genes.