Nanosized DNA Hydrogel Functionalized with a DNAzyme Tetrahedron for Highly Efficient Gene Silencing

DNAzymes are DNA oligonucleotides that have catalytic activity without the assistance of protein enzymes. In particular, RNA-cleaving DNAzymes were considered as ideal candidates for gene therapy due to their unique characteristics. Nevertheless, efforts to use DNAzyme as a gene therapeutic agent are limited by issues such as their low physiological stability in serum and intracellular delivery efficiency. In this study, we developed a nanosized synthetic DNA hydrogel functionalized with a DNAzyme tetrahedron (TDz Dgel) to overcome these limitations. We observed remarkable improvement in the gene-silencing effect as well as intracellular uptake without the support of gene transfection reagents using TDz Dgel. The improved catalytic activity of the DNAzyme resulted from the combination of the cell-penetrating DNA tetrahedron structure and high stability of DNA hydrogel. We envision that this approach will become a convenient and efficient strategy for gene-silencing therapy using DNAzyme in the future.