Suppression of HIV-1 Replication by a Combination of Endonucleolytic Ribozymes (RNase P and tRNase ZL)

• Published in: Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2006-01, Vol.25 (4-6), p.427-437
• Main Authors: Ikeda, Masahiro, Habu, Yuichiro, Miyano-Kurosaki, Naoko, Takaku, Hiroshi
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cercopithecus aethiops; COS Cells; Endoribonucleases - genetics; Endoribonucleases - metabolism; External guide sequence; Gene Products, tat - genetics; Gene Products, vif - genetics; Gene therapy; Genetic Therapy; HIV-1; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Molecular Sequence Data; Nucleic Acid Conformation; Ribonuclease P - genetics; Ribonuclease P - metabolism; RNA, Catalytic - genetics; RNA, Catalytic - metabolism; RNA, Small Interfering - metabolism; RNA, Viral - genetics; RNA, Viral - metabolism; RNase P; tat Gene Products, Human Immunodeficiency Virus; tRNase ZL; vif Gene Products, Human Immunodeficiency Virus; Virus Replication
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/01457630600684120

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 vif regions 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.