Suppression of HIV-1 replication by a combination of endonucleolytic ribozymes (RNase P and tRNnase ZL).
We examined the combinatorial action of RNase P and tRNase ZL-mediated specific inhibition of HIV-1 in cultured cells. We designed two short extra guide sequences (sEGS) that specifically recognize the tat and vifregions of HIV-1 mRNA and mediate the subsequent cleavage of hybridized mRNA by the RNase P and tRNase ZL components. We constructed an RNase P and tRNase ZL-associated vif and tat sEGS expression vector; which used the RNA-polymerase III dependent U6 promoter, as an expression cassette for EGS. Together, the RNase P and tRNase ZL-associated sEGS molecules allow more efficient suppression of HIV-1 mRNA production when separately applied. The possibilities offered by the vector to encode sEGS will provide a powerful tool for gene therapy.
Ikeda
Masahiro
M
Department of Life and Environmental Science, Faculty of Engineering, Chiba Institute of Technology, Narashino, Chiba, Japan.
Habu
Yuichiro
Y
Miyano-Kurosaki
Naoko
N
Takaku
Hiroshi
H
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D015696:Gene Products, tat / Q000235:genetics; D016346:Gene Products, vif / Q000235:genetics; D015316:Genetic Therapy; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D043262:Ribonuclease P / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D016346:Gene Products, vif; D016337:RNA, Catalytic; D034741:RNA, Small Interfering; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; D004722:Endoribonucleases; D043262:Ribonuclease P