Design and anti-HIV-1 activity of hammerhead and hairpin ribozymes containing a stable loop.
Three ribozymes, a hairpin ribozyme (HR112) and two hammerhead ribozymes (RZ115 and RZ119) containing a 5'C(UUCG)G3' loop were designed to cleave the U5 region in the long terminal repeat (LTR) of HIV-1 RNA. The t1/2 values of chemically synthesized substrates mediated by three ribozymes were measured. The transformed CEM cells possessing these three ribozyme-encoding genes were challenged with a HIV-1IIIB strain, and two of these three ribozymes, HR112 and RZ119, were shown to possess strong anti-HIV-1 activity.
Koizumi
M
M
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan. koizum@shina.sankyo.co.jp
Ozawa
Y
Y
Yagi
R
R
Nishigaki
T
T
Kaneko
M
M
Oka
S
S
Kimura
S
S
Iwamoto
A
A
Komatsu
Y
Y
Ohtsuka
E
E
D019380:Anti-HIV Agents / Q000737:chemistry*; D001483:Base Sequence; D015195:Drug Design; D016655:HIV Core Protein p24 / Q000235:genetics; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D016337:RNA, Catalytic / Q000737:chemistry*; D012367:RNA, Viral / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D016337:RNA, Catalytic; D012367:RNA, Viral