1. Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA to immune cells
- Author
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Masayuki Endo, Kohta Mohri, Yoshinobu Takakura, Makiya Nishikawa, Eri Kusuki, Hiroshi Sugiyama, Kumi Hidaka, Shozo Ohtsuki, Yuki Takahashi, and Natsuki Takahashi
- Subjects
chemistry.chemical_classification ,DNA ligase ,Dendrimers ,Polymers and Plastics ,Macrophages ,Bioengineering ,DNA Ligases ,DNA ,Biology ,Cell biology ,Cell Line ,Biomaterials ,chemistry.chemical_compound ,Mice ,Immune system ,CpG site ,chemistry ,Biochemistry ,Cell culture ,Dendrimer ,Materials Chemistry ,Animals ,Tumor necrosis factor alpha ,CpG Islands - Abstract
DNA dendrimers consisting of several branched DNA units connected to each other using DNA ligase were quite effective for the delivery of immunostimulatory CpG DNA to immune cells. Therapeutic application of such DNA dendrimers, however, is hampered by the use of the ligase. Here, we report that self-assembling DNA dendrimers with high immunostimulatory potency can be prepared without DNA ligases. Annealing of DNA consisting of DNA units with elongated adhesive ends resulted in the formation of DNA dendrimers. Atomic force microscopy revealed that the several preparations of DNA dendrimers resulted in dendritic structures as designed. The cellular uptake of DNA dendrimers by mouse macrophage-like RAW264.7 cells and subsequent release of tumor necrosis factor-α were dependent on the structural complexity of the dendrimers. These results indicate that the ligation-free, self-assembling DNA dendrimers are a potent system for the delivery of immunostimulatory CpG DNA to immune cells.
- Published
- 2015