Suppression of HIV-1 Replication by a Combination of Endonucleolytic Ribozymes (RNase P and tRNase ZL) |
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| Authors: | Masahiro Ikeda Yuichiro Habu Naoko Miyano-Kurosaki Hiroshi Takaku |
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| Institution: | 1. Department of Life and Environmental Science, Faculty of Engineering , Chiba Institute of Technology , Narashino , Chiba , Japan;2. High Technology Research Center , Chiba Institute of Technology , Narashino , Chiba , Japan;3. Japanese Foundation for AIDS Prevention, Toranomon , Minato-ku, Tokyo , Japan;4. Department of Life and Environmental Science, Faculty of Engineering, and High Technology Research Center , Chiba Institute of Technology , Narashino , Chiba , Japan |
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| Abstract: | 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. |
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| Keywords: | RNase P tRNase ZL External guide sequence HIV-1 Gene therapy |
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