Antisense phosphorothioate oligonucleotides targeted to the human chemokine receptor CXCR4.
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.
Kusunoki
A
A
Department of Industrial Chemistry, Chiba Institute of Technology, Narashino, Japan.
Miyano-Kurosaki
N
N
Kimura
T
T
Takai
K
K
Yamamoto
N
N
Gushima
H
H
Takaku
H
H
D001483:Base Sequence; D006367:HeLa Cells; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000187:drug effects*; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D019718:Receptors, CXCR4; D013873:Thionucleotides