Antisense Oligodeoxynucleotide Complementary to CXCR4 mRNA Block Replication of HIV-1 in COS Cells |
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| Authors: | Akiko Kusunoki Akira Wada Naoko Kurosaki Tohru Kimura Kazuyuki Takai Naoki Yamamoto |
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| Institution: | 1. Department of Industrial Chemistry , Chiba Institute of Technology , 2-17-1 Tsudanuma, Narashino-shi, Chiba, 275-0016, Japan;2. Department of Microbiology , Tokyo Medical and Dental University School of Medicine , 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113, Japan |
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| Abstract: | Abstract CXCR4 is both a chemokine receptor and an entry co-receptor for the T-cell line-adapted human immunodeficiency virus type 1 (HIV-1). To find a more efficacious therapeutic treatement of acquied immunodeficiency syndrome, we exmined the effects of antisense oligonucleotides on CXCR4 production. COS cells, stably expressing CXCR4 and CD4, were incubated with several kinds of oligonucleotides. Total human p24 antigen production was determined using an enzyme-linked immunosorbent assay system. An antisense phosphorothioate-modified oligonucleotide, complementary to the translation region of the CXCR4 mRNA, showed minimal inhibition of p24 antigen production at the high concentration of 2μM. On the other hand, the antisense phosphorothioate oligonucleotide, when used with transfection reagents, showed high efficiency at low concentrations, and confirmed the sequence-specific action. Interestingly, the oligonucleotide with the natual phosphodiester backbone, when used with the transfection reagents, also had high functional effects, comparable to the modified oligonucleotide. This defines the prerequisite criteria necessary for the design and the application of antisense oligonucleotides against HIV-1 in vivo. |
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