Antisense oligodeoxynucleotide complementary to CXCR4 mRNA block replication of HIV-1 in COS cells.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Antisense oligodeoxynucleotide complementary to CXCR4 mRNA block replication of HIV-1 in COS cells.

Nucleosides Nucleotides. 1999 Jun-Jul;18(6-7):1705-8. Unique Identifier : AIDSLINE MED/99403459
Kusunoki A; Wada A; Kurosaki N; Kimura T; Takai K; Yamamoto N; Takaku H; Department of Industrial Chemistry, Chiba Institute of; Technology, Japan.

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 treatment of acquired immunodeficiency syndrome, we examined 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 initiation region of the CXCR4 mRNA, showed minimal inhibition of p24 antigen production at the high concentration of 2 microM. 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 natural phosphodiester backbone, when used with the transfection reagents, also had high functional effects, comparable to the modified oligonucleotide. This study defines the prerequisite criteria necessary for the design and the application of antisense oligonucleotides against HIV-1 in vivo.

Keywords: JOURNAL ARTICLE Animal Base Sequence Codon COS Cells Human HIV-1/*DRUG EFFECTS/PHYSIOLOGY Oligonucleotides, Antisense/*PHARMACOLOGY Receptors, CXCR4/*GENETICS RNA, Messenger/*GENETICS Tumor Cells, Cultured Virus Replication/*DRUG EFFECTS
991230
A99C0991

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