Zhou Jiehua, Rossi John J
Division of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, City of Hope, Duarte, CA, USA.
Methods Mol Biol. 2011;721:355-71. doi: 10.1007/978-1-61779-037-9_22.
The highly specific mechanism of RNA (RNAi) that inhibits the expression of disease genes is increasingly being harnessed to develop a new class of therapeutics for a wide variety of human maladies. The successful use of small interfering RNAs (siRNAs) for therapeutic purposes requires safe and efficient delivery to specific cells and tissues. Herein, we demonstrate novel cell type-specific dual inhibitory function anti-gp120 aptamer-siRNA delivery systems for HIV-1 therapy, in which both the aptamer and the siRNA portions have potent anti-HIV activities. The envelope glycoprotein is expressed on the surface of HIV-1 infected cells, allowing binding and internalization of the aptamer-siRNA chimeric molecules. The Dicer substrate siRNA delivered by the aptamers is functionally processed by Dicer, resulting in specific inhibition of HIV-1 replication and infectivity in cultured CEM T-cells and primary blood mononuclear cells. Our results provide a set of novel aptamer-targeted RNAi therapeutics to combat HIV and further validate the use of anti-gp120 aptamers for delivery of Dicer substrate siRNAs.
抑制疾病基因表达的高度特异性RNA机制（RNA干扰，RNAi）越来越多地被用于开发针对各种人类疾病的新型治疗方法。将小干扰RNA（siRNA）成功用于治疗目的需要安全有效地递送至特定细胞和组织。在此，我们展示了用于HIV-1治疗的新型细胞类型特异性双抑制功能抗gp120适配体-siRNA递送系统，其中适配体和siRNA部分均具有强大的抗HIV活性。包膜糖蛋白在HIV-1感染细胞表面表达，使得适配体-siRNA嵌合分子能够结合并内化。由适配体递送的Dicer底物siRNA经Dicer进行功能加工，从而在培养的CEM T细胞和原代血液单核细胞中特异性抑制HIV-1复制和感染性。我们的结果提供了一组用于对抗HIV的新型适配体靶向RNAi治疗方法，并进一步验证了抗gp120适配体用于递送Dicer底物siRNA的用途。
