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Title: Optimal Arrangement of Four Short DNA Strands for Delivery of Immunostimulatory Nucleic Acids to Immune Cells.
Authors: Ohtsuki, Shozo
Matsuzaki, Noriyuki
Mohri, Kohta
Endo, Masayuki  kyouindb  KAKEN_id
Emura, Tomoko
Hidaka, Kumi
Sugiyama, Hiroshi  kyouindb  KAKEN_id
Takahashi, Yuki  kyouindb  KAKEN_id
Ishiyama, Kenichi
Kadowaki, Norimitsu
Takakura, Yoshinobu  kyouindb  KAKEN_id
Nishikawa, Makiya
Author's alias: 西川, 元也
Issue Date: 17-Sep-2015
Publisher: Mary Ann Liebert Inc.
Journal title: Nucleic acid therapeutics
Volume: 25
Issue: 5
Start page: 245
End page: 253
Abstract: Nanosized DNA assemblies are useful for delivering immunostimulatory cytosine-phosphate-guanine (CpG) DNA to immune cells, but little is known about the optimal structure for such delivery. In this study, we designed three different DNA nanostructures using four 55-mer oligodeoxynucleotides (ODNs), that is, tetrapod-like structured DNA (tetrapodna), tetrahedral DNA (tetrahedron), and tetragonal DNA (tetragon), and compared their potencies. Electrophoresis showed that tetrapodna was obtained with high yield and purity, whereas tetrahedron formed multimers at high ODN concentrations. Atomic force microscopy revealed that all preparations were properly constructed under optimal conditions. The thermal stability of tetrapodna was higher than those of the others. Dynamic light scattering analysis showed that all of the assemblies were about 8 nm in diameter. Upon addition to mouse macrophage-like RAW264.7 cells, tetrahedron was most efficiently taken up by the cells. Then, a CpG DNA, a ligand for toll-like receptor 9, was linked to these DNA nanostructures and added to RAW264.7 cells. CpG tetrahedron induced the largest amount of tumor necrosis factor-α, followed by CpG tetrapodna. Similar results were obtained using human peripheral blood mononuclear cells. Taken together, these results indicate that tetrapodna is the best assembly with the highest yield and high immunostimulatory activity, and tetrahedron can be another useful assembly for cellular delivery if its preparation yield is improved.
Rights: Final publication is available from Mary Ann Liebert, Inc., publishers
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1089/nat.2014.0524
PubMed ID: 26222130
Appears in Collections:Journal Articles

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