Targeting and Understanding HIV Latency: The CRISPR System against the Provirus

Magro, Gloria; Calistri, Arianna; Parolin, Cristina

doi:10.3390/pathogens10101257

Cited by 7 publications

(5 citation statements)

References 85 publications

(120 reference statements)

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“…On the one hand, the development of gene editing tools, including zinc finger nucleases (ZFNs) [111], transcription activator-like effector nucleases (TALENs) [112], and the CRIPSR-Cas9 system [113], has created novel strategies to tackle viral latency in the field of HIV persistence. These advancements may include (a) directly targeting the virus in its integrated or non-integrated forms, (b) modulating its transcription as a "block and lock" [114] or "shock and kill" [115] strategies by using catalytically inactive Cas9 [116,117], (c) targeting host genes involved in the viral replication cycle (such CCR5) [118], and (d) discovering novel host molecular genes involved in the viral replication cycle using CRISPR as a screening tool [119].One of the novelties brought by the CRISPR-Cas9 system is the simpleness of the model, as CRISPR-Cas9 technology uses RNA as a guide to target directly objective genes, making it easier to design than ZFNs and TALENs.…”

Section: Genetic and Epigenetic Modulation To Impact Hiv Transcriptionmentioning

confidence: 99%

Targeting Viral Transcription for HIV Cure Strategies

Izquierdo-Pujol,

Puertas,

Martinez-Picado

et al. 2024

Microorganisms

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Combination antiretroviral therapy (ART) suppresses viral replication to undetectable levels, reduces mortality and morbidity, and improves the quality of life of people living with HIV (PWH). However, ART cannot cure HIV infection because it is unable to eliminate latently infected cells. HIV latency may be regulated by different HIV transcription mechanisms, such as blocks to initiation, elongation, and post-transcriptional processes. Several latency-reversing (LRA) and -promoting agents (LPA) have been investigated in clinical trials aiming to eliminate or reduce the HIV reservoir. However, none of these trials has shown a conclusive impact on the HIV reservoir. Here, we review the cellular and viral factors that regulate HIV-1 transcription, the potential pharmacological targets and genetic and epigenetic editing techniques that have been or might be evaluated to disrupt HIV-1 latency, the role of miRNA in post-transcriptional regulation of HIV-1, and the differences between the mechanisms regulating HIV-1 and HIV-2 expression.

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Section: Genetic and Epigenetic Modulation To Impact Hiv Transcriptionmentioning

confidence: 99%

Targeting Viral Transcription for HIV Cure Strategies

Izquierdo-Pujol,

Puertas,

Martinez-Picado

et al. 2024

Microorganisms

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“…Bogerd et al used a Cas9-based approach to induce the expression of restriction factors APOBEC3G (A3G) and APOBEC3B (A3B) in human cells ( 91 ). The CRISPR knockout screening approach can be used to identify new host genes involved in the virus replication cycle ( 92 ).…”

Section: Rna Therapeutic Strategiesmentioning

confidence: 99%

Strategies for HIV-1 suppression through key genes and cell therapy

Sorokina,

Anchakova,

Dashinimaev

2023

Front. Med.

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Human immunodeficiency virus type 1 (HIV-1) remains a significant challenge for global public health as limited therapeutic options are available for HIV-infected individuals receiving combination antiretroviral therapy. Additionally, individuals with HIV-1/acquired immunodeficiency syndrome (AIDS) complications have a reduced life expectancy. In recent decades, gene and cell-based strategies have shown promise in achieving a functional cure for HIV-1 infection. The outcomes of therapies with patients in Berlin and London have led to moderate optimism for a highly effective HIV-1 treatment. This review categorizes current strategies for HIV-1 treatment into RNA- and antibody-based therapies, cell and genome editing approaches, and methods for eradicating latent reservoirs. These findings demonstrate how the use of various anti-HIV-1 agents enhances our understanding of HIV-1 infection and may provide important insights for potential HIV-1 treatment.

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“…Cas12a was assessed by Gao et al due to its smaller size and better ability to accommodate multiple crRNAs under a single Pol III promoter [ 30 ]. Experiments with Cas12a showed more sustained antiviral activity in comparison to Cas9 [ 57 ]. The RNA-editing Cas13 system has been recently tested against HIV-1 infected cells.…”

Section: Crispr/cas Mediated Inhibition Of Hiv-1mentioning

confidence: 99%

CRISPR/Cas9: a tool to eradicate HIV-1

Bhowmik

Chaubey

2022

AIDS Res Ther

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The development of antiretroviral therapy (ART) has been effective in suppressing HIV replication. However, severe drug toxicities due to the therapy and its failure in targeting the integrated proviral genome have led to the introduction of a new paradigm of gene-based therapies. With its effective inhibition and high precision, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) or CRISPR/Cas9 has emerged as an effective genome editing tool in the last decade. Mediated by guide RNAs (gRNAs), Cas9 endonuclease acts like genetic scissors that can modify specific target sites. With this concept, CRISPR/Cas9 has been used to target the integrated proviral HIV-1 genome both in in vitro as well as in vivo studies including non-human primates. The CRISPR has also been tested for targeting latent HIV-1 by modulating the proviral transcription with the help of a specialized Cas9 mutant. Overcoming the limitations of the current therapy, CRISPR has the potential to become the primary genome editing tool for eradicating HIV-1 infection. In this review, we summarize the recent advancements of CRISPR to target the proviral HIV-1 genome, the challenges and future prospects.

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Targeting and Understanding HIV Latency: The CRISPR System against the Provirus

Cited by 7 publications

References 85 publications

Targeting Viral Transcription for HIV Cure Strategies

Targeting Viral Transcription for HIV Cure Strategies

Strategies for HIV-1 suppression through key genes and cell therapy

CRISPR/Cas9: a tool to eradicate HIV-1

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