Antisense Phosphorothioate Oligonucleotides Targeted to the Human Chemokine Receptor CXCR4 |
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| Authors: | Akiko Kusunoki Naoko Miyano-kurosaki Tohru Kimura Kazuyuki Takai Naoki Yamamoto Hiroshi Gushima |
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| Institution: | 1. Department of Industrial Chemistry , Chiba Institute of Technology , 2-17-1 Tsudanuma, Narashino , Chiba , 275-0016 , Japan;2. Department of High Technology Research Center , Chiba Institute of Technology , 2-17-1 Tsudanuma, Narashino , Chiba , 275-0016 , Japan;3. Department of Microbiology , Tokyo Medical and Dental University, School of Medicine , 1-5-45 Yushima, Bunkyo-ku, Tokyo , 113-8519 , Japan;4. Department of Industrial Chemistry , Chiba Institute of Technology , 2-17-1 Tsudanuma, Narashino , Chiba , 275-0016 , Japan;5. Department of High Technology Research Center , Chiba Institute of Technology , 2-17-1 Tsudanuma, Narashino , Chiba , 275-0016 , Japan;6. R&7. D Planning &8. Administration Department Affiliation , Yamanouchi Pharmaceutical Co., Ltd. , 3-17-1 Hasune, Itabashi-ku, Tokyo , 174-8612 , Japan |
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| Abstract: | Abstract The CXC chemokine receptor CXCR4 is used as a major co-receptor for fusion and entry by syncytia-inducing T-tropic (X4) isolates of HIV-1. In the present study, we report the effects of an antisense oligodeoxyribonucleotide on the inhibition of CXCR4 gene expression in X4 HIV-1 infected HeLa-CD4 cells, to find more efficacious therapeutic possibilities for Human Immunodeficiency Virus type 1 (HIV-1) infection. Antisense phosphorothioate oligodeoxyribonucleotides (anti-S-ODNs) corresponding to the sequence of bases 69 to 88 of the human CXCR4 mRNA gene were synthesized. When the naked anti-S-ODN was incubated with HeLa-CD4 cells, the surface levels of this chemokine receptor were reduced up to 50%, indicating sequence-specific inhibition. We also examined the concomitant use of a basic peptide transfection reagent, nucleosomal histone proteins (RNP), for delivery of anti-S-ODNs. The anti-S-ODN encapsulated with RNP had higher inhibitory effects on p24 products than the naked anti-S-ODN. |
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