Antisense phosphorothioate oligonucleotides targeted to the human chemokine receptor CXCR4

The CXC chemokine receptor CXCR4 is used as a major cc-receptor for fusion and entry by syncytia-inducing T-tropic (X4) isolates of HIV-1. In the pres ent study, we report the effects of an antisense: oligodeoxyribonucleotide on the inhibition of CXCR4 gene expression in X4 HIV-1 infected HeLa-CD4 ce lls, to find more efficacious therapeutic possibilities for Human Immunodef iciency Virus type 1 (HIV-1) infection. Antisense phosphorothioate oligodeo xyribonucleotides (anti-S-ODNS) corresponding to the sequence of bases 69 t o 88 of the human CXCR4 mRNA gene were synthesized. When the naked anti-S-O DN was incubated with HeLa-CD4 cells, the surface levels of this chemokine receptor were reduced up to 50%, indicating sequence-specific inhibition. W e 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.