Unwalla Hoshang J, Li Ming-Jie, Kim James D, Li Hai Tang, Ehsani Ali, Alluin Jessica, Rossi John J
Nat Biotechnol. 2004 Dec;22(12):1573-8. doi: 10.1038/nbt1040. Epub 2004 Nov 28.
Here we demonstrate that an inducible anti-HIV short hairpin RNA (shRNA) expressed from a Pol II promoter inhibits HIV-1 gene expression in mammalian cells. Our strategy is based on a promoter system in which the HIV-1 LTR is fused to the Drosophila hsp70 minimal heat shock promoter. This system is inducible by HIV-1 TAT, which functions in a negative feedback loop to activate transcription of an shRNA directed against HIV-1 rev. Upon induction the shRNA is processed to an siRNA that guides inhibition of HIV replication in cultured T-lymphocytes and hematopoietic stem cell-derived monocytes. The fusion promoter system may be safer than drug-inducible systems for shRNA-mediated gene therapy against HIV as the shRNAs are only expressed following HIV infection.
在此，我们证明了从Pol II启动子表达的可诱导抗HIV短发夹RNA（shRNA）可抑制哺乳动物细胞中的HIV-1基因表达。我们的策略基于一种启动子系统，其中HIV-1长末端重复序列（LTR）与果蝇hsp70最小热休克启动子融合。该系统可被HIV-1反式激活因子（TAT）诱导，TAT在负反馈回路中发挥作用，激活针对HIV-1 rev的shRNA的转录。诱导后，shRNA被加工成小干扰RNA（siRNA），后者可指导抑制培养的T淋巴细胞和造血干细胞来源的单核细胞中的HIV复制。对于针对HIV的shRNA介导的基因治疗，融合启动子系统可能比药物诱导系统更安全，因为shRNA仅在HIV感染后才表达。
