Modulation of immunostimulatory activity of CpG oligonucleotides by site-specific deletion of nucleobases

被引:45
作者
Yu, D [1 ]
Kandimalla, ER [1 ]
Zhao, QY [1 ]
Cong, YP [1 ]
Agrawal, S [1 ]
机构
[1] Hybridon Inc, Cambridge, MA 02139 USA
关键词
D O I
10.1016/S0960-894X(01)00418-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The effect of nucleobase deletion in the 3 '- or the 5 ' -flanking sequence to a CpG-motif on immunostimulatory activity of CpG-containing oligonucleotides was examined by cell proliferation, secretion of IL-12 and IL-6 in mouse spleen cell cultures, and by spleen enlargement in mice. Deletion of one or two nucleobases in the 3 ' -flanking sequence to a CpG-motif at certain positions did not affect immunostimulatory activity, while similar deletions in the 5 ' -flanking sequence increased immunostimulatory activity compared with the parent oligo. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:2263 / 2267
页数:5
相关论文
共 14 条
[1]   CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans [J].
Davis, HL ;
Suparto, I ;
Weeratna, R ;
Jumintarto ;
Iskandriati, D ;
Chamzah, S ;
Ma'ruf, A ;
Nente, C ;
Pawitri, D ;
Krieg, AM ;
Heriyanto ;
Smits, W ;
Sajuthi, D .
VACCINE, 2000, 18 (18) :1920-1924
[2]   DNA vaccines: Immunology, application, and optimization [J].
Gurunathan, S ;
Klinman, DM ;
Seder, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :927-974
[3]   Effect of chemical modifications of cytosine and guanine in a CpG-Motif of oligonucleotides: Structure-immunostimulatory activity relationships [J].
Kandimalla, ER ;
Yu, D ;
Zhao, QY ;
Agrawal, S .
BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (03) :807-813
[4]   CPG MOTIFS IN BACTERIAL-DNA TRIGGER DIRECT B-CELL ACTIVATION [J].
KRIEG, AM ;
YI, AK ;
MATSON, S ;
WALDSCHMIDT, TJ ;
BISHOP, GA ;
TEASDALE, R ;
KORETZKY, GA ;
KLINMAN, DM .
NATURE, 1995, 374 (6522) :546-549
[5]   The influence of base sequence on the immunostimulatory properties of DNA [J].
Pisetsky, DS .
IMMUNOLOGIC RESEARCH, 1999, 19 (01) :35-46
[6]  
Pisetsky DS, 2000, CURR TOP MICROBIOL, V247, P143
[7]  
Tighe H, 2000, EUR J IMMUNOL, V30, P1939, DOI 10.1002/1521-4141(200007)30:7<1939::AID-IMMU1939>3.0.CO
[8]  
2-#
[9]  
Tokunaga T, 1999, JPN J INFECT DIS, V52, P1
[10]   Accessible 5′-end of CpG-containing phosphorothioate oligodeoxynucleotides is essential for immunostimulatory activity [J].
Yu, D ;
Zhao, Q ;
Kandimalla, ER ;
Agrawal, S .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (23) :2585-2588