Related Experiment Video
Updated: Oct 19, 2025
06:46
Isolation of Exosomes from the Plasma of HIV-1 Positive Individuals
Published on: January 5, 2016
17.6K
Exosome-mediated stable epigenetic repression of HIV-1
Surya Shrivastava1, Roslyn M Ray1, Leo Holguin1
1Center for Gene Therapy, City of Hope-Beckman Research Institute, Duarte, CA, USA.
Nature Communications
|September 21, 2021
Summary
Researchers developed a novel exosome therapy to epigenetically repress Human Immunodeficiency Virus (HIV-1). This "block and lock" approach uses engineered exosomes to deliver a repressor, offering a safer, long-term strategy against persistent HIV-1 infection.
Area of Science:
- Epigenetics
- Virology
- Nanomedicine
Background:
- Human Immunodeficiency Virus (HIV-1) establishes persistent latent infections, challenging current treatments.
- Combination antiretroviral therapy (cART) for HIV-1 has limitations, including side effects and drug resistance.
- A safer, in vivo therapeutic strategy is needed to achieve stable, long-term repression of HIV-1.
Purpose of the Study:
- To develop a novel therapeutic strategy for stable epigenetic repression of HIV-1.
- To engineer exosomes for in vivo delivery of an HIV-1 repressor.
- To investigate the efficacy of exosome-mediated epigenetic silencing of HIV-1.
Main Methods:
- Development of a Zinc Finger Protein (ZFP-362) fused to DNA methyltransferase 3A to target and repress the HIV-1 promoter.
- Engineering cells to produce exosomes containing RNA encoding the HIV-1 repressor.
- Administration of anti-HIV-1 exosomes to humanized NSG mouse models.
Main Results:
- Engineered exosomes successfully delivered the HIV-1 repressor protein.
- Exosome-mediated delivery resulted in suppression of HIV-1 expression.
- Epigenetic repression, specifically DNA methylation of HIV-1, was identified as the mechanism of suppression.
Conclusions:
- Exosome-mediated delivery of therapeutic cargo offers a promising platform for systemic treatment of HIV-1.
- This approach achieves stable, long-term epigenetic repression of HIV-1, offering a potential "block and lock" strategy.
- The findings pave the way for developing safer, more effective therapies for persistent HIV-1 infections.
Related Concept Videos
01:26Size and Structure of Viral Genomes
259
Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
259
03:17Inheritance of Chromatin Structures
6.8K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.8K
01:52Eukaryotic Transcription Inhibitors
10.1K
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...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.1K
01:29Viruses with RNA Genomes
246
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
246
01:36Overview of Exosomes
3.0K
Exosomes are stable, lipid bilayer-enclosed vesicles capable of crossing biological barriers. They can carry a wide range of molecules required for intercellular communication. Once exosomes are released from the cell where they originated, they enter a recipient cell through various pathways such as fusion, receptor-mediated endocytosis, macropinocytosis, and phagocytosis.
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
Stahl et al. discovered exosomes in 1983, but the exosomes were initially considered waste products released from the...
3.0K
02:30siRNA - Small Interfering RNAs
17.3K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
17.3K