DNA is a natural, biocompatible, biodegradable, bioactive, and arbitrarily designable polymer. These features of DNA promise its use as a material for the construction of delivery systems for bioactive compounds. Long double-stranded DNA, such as plasmid DNA, can be used for the delivery of therapeutic genes and anticancer agents, but their tissue distribution, as well as interaction with cells, is hardly able to be manipulated. Nanosized DNA constructs, which can be prepared by using two or more oligodeoxynucleotides (ODNs), can have diverse features from simple double-stranded DNA depending on their structure. Based on this difference, we have developed a variety of nanostructured DNAs with unique features and evaluated their physicochemical, biological and therapeutic properties. We first designed multibranched DNA nanostructures and obtained them with high yield. Tripod-like nanostructured DNA, or tripodna, was effective in increasing the retention of a phosphorodiamidate morpholino oligomer in the systemic circulation after intravenous injection into mice. In addition, cytokine release by unmethylated cytosine-phosphate-guanine (CpG) ODN was significantly increased by its incorporation into tripodna or hexapod-like nanostructured DNA, or hexapodna. We also succeeded in preparing DNA hydrogel by self-assembling of hexapodna with adhesive single-stranded tails. The DNA hydrogel obtained was injectable through a 27-G needle, and immediately regelated after injection. DNA hydrogels constructed with CpG ODNs, or CpG DNA hydrogels, were effective in the stimulation of innate immunity and in the sustained release of biomolecules incorporated into the hydrogels. CpG DNA hydrogel containing an ovalbumin (OVA)-derived antigen peptide significantly retarded the tumor growth in mouse T cell lymphoma EG7-OVA tumor-bearing mice. We also succeeded in incorporating dendritic cells together with the antigen into the hydrogel, which was effective in inhibiting tumor growth. These results indicate that nanostructured DNA is suitable for the <i>in vivo</i> delivery of biomolecules and cells.

Nanostructured DNA for the <i>in vivo</i> delivery of biomolecules and cells

2019 Spring National Meeting

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Nanostructured DNA for the in vivo delivery of biomolecules and cells