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タイトル: Structural and immunostimulatory properties of Y-shaped DNA consisting of phosphodiester and phosphorothioate oligodeoxynucleotides.
著者: Matsuoka, Nao
Nishikawa, Makiya  kyouindb  KAKEN_id
Mohri, Kohta
Rattanakiat, Sakulrat
Takakura, Yoshinobu  kyouindb  KAKEN_id
著者名の別形: 西川, 元也
キーワード: Immunostimulatory DNA
Phosphorothioate modification
Nano-assembly
Thermostability
Macrophage
CpG motif
発行日: 20-Dec-2010
出版者: Elsevier B.V.
誌名: Journal of controlled release : official journal of the Controlled Release Society
巻: 148
号: 3
開始ページ: 311
終了ページ: 316
抄録: Y-shape formation increased the immunostimulatory activity of phosphodiester (PO) oligodeoxynucleotides (ODNs) containing CpG motif. In this study, PO CpG ODN or CpG ODN containing nuclease-resistant phosphorothioate (PS) linkages, i.e., PS CpG ODN or PO CpG ODN with three PS linkages at the both ends (PS3), was mixed with two PO- or PS ODNs to prepare Y-shaped DNA (Y-DNA) containing a potent CpG motif. The melting temperature of Y-DNA decreased with increasing number of PS linkages. Y(PS/PO/PO), which contained PS CpG ODN, showed the greatest activity to induce tumor necrosis factor-α release from macrophage-like RAW264.7 cells, followed by Y(PS3/PO/PO). However, the high activity of Y(PS/PO/PO) was due to that of PS CpG ODN, and Y-shape formation had no significant effect on the activity. Furthermore, PS CpG ODN of Y(PS/PO/PO) was efficiently taken up by cells, but other PO ODNs in the Y-DNA were not, indicating that PS CpG ODN in Y-DNA behave like single stranded PS CpG ODN. In quite contrast, the immunostimulatory activity of PS3 CpG ODN was significantly increased by Y-shape formation. In conclusion, Y-shape formation and PS substitution can be used simultaneously to increase the immunostimulatory activity of CpG ODN, but extensive substitution should be avoided because it diminishes the benefits of Y-shape formation.
著作権等: © 2010 Elsevier B.V.
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。
URI: http://hdl.handle.net/2433/134574
DOI(出版社版): 10.1016/j.jconrel.2010.09.019
PubMed ID: 20887761
出現コレクション:学術雑誌掲載論文等

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