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

Abstract

Topoisomerase II beta (Topo IIβ) is one of the two isoforms of type II topoisomerases present in higher eukaryotes. This 180kDa 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.