HIV-1 RT-dependent DNAzyme expression inhibits HIV-1 replication without the emergence of escape viruses
HIV-1 RT-dependent DNAzyme expression inhibits HIV-1 replication without the emergence of escape viruses
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HIV-1 RT依赖性DNA酶表达抑制HIV-1复制而不出现逃逸病毒
DOI：
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
H. Takaku
中科院分区：
文献类型：
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作者：
Ryuichi Sugiyama;Masaaki Hayafune;Y. Habu;N. Yamamoto;H. Takaku
与核酶相比，dnazyme更容易制备，对化学和酶降解的敏感性更低；然而，DNA酶表达系统尚未开发。在这项研究中，我们探索了HIV-1逆转录（RT）在DNA酶表达系统中的机制。我们构建了HIV-1 rt依赖性慢病毒DNAzyme表达载体，包括HIV-1引物结合位点，DNA酶，天然tRNA (Lys-3), tRMDtRL，或两个截断的tRNA （Lys-3）之一，tRMDΔARMtRL或tRMD3 ' -endtRL。慢病毒载体介导的DNAzyme表达在SupT1细胞中显示出高水平的HIV-1复制抑制。我们还在一项长期试验中证明了这种方法的有效性，在这项试验中，我们发现DNAzymes阻止了HIV的抑制逃脱。这些结果表明，HIV-1 rt依赖性慢病毒载体衍生的DNAzymes可以防止逃逸突变的出现。
DNAzymes are easier to prepare and less sensitive to chemical and enzymatic degradation than ribozymes; however, a DNA enzyme expression system has not yet been developed. In this study, we exploited the mechanism of HIV-1 reverse transcription (RT) in a DNA enzyme expression system. We constructed HIV-1 RT-dependent lentiviral DNAzyme expression vectors including the HIV-1 primer binding site, the DNA enzyme, and either a native tRNA (Lys-3), tRMDtRL, or one of two truncated tRNAs (Lys-3), tRMDΔARMtRL or tRMD3′-endtRL. Lentiviral vector-mediated DNAzyme expression showed high levels of inhibition of HIV-1 replication in SupT1 cells. We also demonstrated the usefulness of this approach in a long-term assay, in which we found that the DNAzymes prevented escape from inhibition of HIV. These results suggest that HIV-1 RT-dependent lentiviral vector-derived DNAzymes prevent the emergence of escape mutations.
影响因子：
12.4
作者：
Li, MJ;Kim, J;Rossi, JJ
通讯作者：
Rossi, JJ
影响因子：
2.9
作者：
Santoro, SW;Joyce, GF
通讯作者：
Joyce, GF