Related Experiment Video

Updated: Oct 9, 2026

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

Inhibition of the human chemokine receptor CXCR4 by antisense phosphorothioate oligodeoxyribonucleotides

A Kusunoki1, T Saitou, N Miyano-Kurosaki

  • 1Department of Industrial Chemistry, Chiba Institute of Technology, Narashino, Chiba, Japan.

FEBS Letters
|February 13, 2001
PubMed

Insights

An antisense oligodeoxynucleotide targeting CXCR4 gene expression inhibited HIV-1 replication. Delivery with RNP enhanced this inhibition, offering a potential therapeutic strategy for HIV-1 infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • CXC chemokine receptor CXCR4 is essential for T-tropic (X4) HIV-1 entry.
  • HIV-1 infection remains a significant global health challenge.
  • Targeting viral entry pathways is a key therapeutic strategy.

Purpose of the Study:

  • To investigate the efficacy of an antisense phosphorothioate oligodeoxyribonucleotide (anti-S-ODN) in inhibiting CXCR4 gene expression.
  • To evaluate the potential of anti-S-ODN as a therapeutic agent against X4 HIV-1 infection.
  • To assess the role of nucleosomal histone proteins (RNP) in enhancing anti-S-ODN delivery and efficacy.

Main Methods:

  • Synthesized and tested various anti-S-ODN sequences for their inhibitory effects on HIV-1 gag p24 production in HeLa-CD4 cells.
  • Utilized a basic peptide transfection reagent, RNP, for the delivery of anti-S-ODN.
  • Quantified the suppression of CXCR4 surface levels on treated cells to confirm sequence-specific inhibition.

Main Results:

  • The anti-S-ODN-1 sequence demonstrated a notable inhibitory effect on HIV-1 gag p24 production.
  • Encapsulation of anti-S-ODN-1 with RNP significantly enhanced its inhibitory activity compared to naked anti-S-ODN-1.
  • Incubation with RNP-encapsulated anti-S-ODN-1 led to substantial suppression of CXCR4 surface expression, confirming sequence-specific gene silencing.

Conclusions:

  • Antisense oligodeoxyribonucleotides targeting CXCR4 show promise for inhibiting HIV-1 replication.
  • RNP-mediated delivery enhances the efficacy of antisense oligodeoxyribonucleotides.
  • This approach presents a potential therapeutic avenue for managing HIV-1 infection by blocking viral entry.

More Related Videos

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...