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载有 c 端脱铁转铁蛋白的纳米粒介导的拓扑异构酶 IIβ 基因特异性 siRNA 的递呈及其对 HIV-1 复制的影响。

Topoisomerase II β Gene Specific siRNA Delivery by Nanoparticles Prepared with c-ter Apotransferrin and its Effect on HIV-1 Replication.

机构信息

Laboratory of Molecular Therapeutics, Department of Biotechnology and Bioinformatics, School of Life Sciences, South Campus, University of Hyderabad, Prof. C. R. Rao Road, Gachibowli, Hyderabad, 500049, Telangana, India.

出版信息

Mol Biotechnol. 2021 Aug;63(8):732-745. doi: 10.1007/s12033-021-00334-7. Epub 2021 May 16.

Abstract

Topoisomerase II beta (Topo IIβ) is one of the two isoforms of type II topoisomerases present in higher eukaryotes. This 180 kDa nuclear protein involves in different cellular processes like transcription, recombination, etc., apart from its normal topological functions. Previously, we have reported the association of this isoform along with the other isoform topoisomerase II alpha (Topo IIα) with HIV-1 reverse transcription complex and the downregulation of Topo IIβ expression resulted in incomplete reverse transcription. In this study, we have tested the Topo IIβ specific siRNA delivery using protein nanoparticles prepared with c-terminal domine of transferrin (c-ter) for the first time. Results show that, c-ter nanoparticles resemble apotransferrin nanoparticles in drug holding capability and drug delivery but with small in size. Topo IIβ specific siRNA delivered in the form of c-ter nanoformulation resulted in knockdown of Topo IIβ expression for the prolonged periods and which intern resulted in decreased viral replication of HIV-1.

摘要

拓扑异构酶 IIβ(Topo IIβ)是高等真核生物中存在的两种 II 型拓扑异构酶同工酶之一。这种 180kDa 的核蛋白除了具有正常的拓扑功能外,还参与转录、重组等不同的细胞过程。以前,我们已经报道了该同工酶与另一种同工酶拓扑异构酶 IIα(Topo IIα)与 HIV-1 逆转录复合物的关联,并且 Topo IIβ 的表达下调导致不完全逆转录。在这项研究中,我们首次使用转铁蛋白(c-ter)C 端结构域制备的蛋白质纳米颗粒测试了 Topo IIβ 特异性 siRNA 的传递。结果表明,c-ter 纳米颗粒在药物保持能力和药物传递方面与脱铁转铁蛋白纳米颗粒相似,但尺寸较小。以 c-ter 纳米制剂形式递呈的 Topo IIβ 特异性 siRNA 可长时间敲低 Topo IIβ 的表达,从而降低 HIV-1 的病毒复制。

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