Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review

Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead...

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Main Authors: Chloë Hanssens, Jolien Van Cleemput
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/7/654
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author Chloë Hanssens
Jolien Van Cleemput
author_facet Chloë Hanssens
Jolien Van Cleemput
author_sort Chloë Hanssens
collection DOAJ
description Background: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to a broad spectrum of clinical manifestations, ranging from mild symptoms to severe disease, particularly in immunocompromised individuals. Clustered regularly interspaced palindromic repeats (CRISPR)-based therapy is an interesting alternative to current antiviral drugs, which fail to cure latent infections and are increasingly challenged by viral resistance. Objective: This scoping review aimed to summarize the current state of CRISPR-based antiviral strategies against herpesvirus infections, highlighting the underlying mechanisms, study design and outcomes, and challenges for clinical implementation. Design: A literature search was conducted in the databases PubMed and Web of Science, using both a general and an individual approach for each herpesvirus. Results: This scoping review identified five main mechanisms of CRISPR-based antiviral therapy against herpesvirus infections in vitro and/or in vivo. First, CRISPR systems can inhibit the active lytic replication cycle upon targeting viral lytic genes or host genes. Second, CRISPR technologies can remove latent viral genomes from infected cells by targeting viral genes essential for latency maintenance or destabilizing the viral genome. Third, reactivation of multiple latent herpesvirus infections can be inhibited by CRISPR-Cas-mediated editing of lytic viral genes, preventing a flare-up of clinical symptoms and reducing the risk of viral transmission. Fourth, CRISPR systems can purposefully induce viral reactivation to enhance recognition by the host immune system or improve the efficacy of existing antiviral therapies. Fifth, CRISPR technology can be applied to develop or enhance the efficiency of cellular immunotherapy. Conclusions: Multiple studies demonstrate the potential of CRISPR-based antiviral strategies to target herpesvirus infections through various mechanisms in vitro and in vivo. However, aspects regarding the delivery and biosafety of CRISPR systems, along with the time window for treatment, require further investigation before broad clinical implementation can be realized.
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spelling doaj-art-3bb7bb3e23894f6690c1eaf6facb84912025-08-20T03:56:46ZengMDPI AGPathogens2076-08172025-07-0114765410.3390/pathogens14070654Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping ReviewChloë Hanssens0Jolien Van Cleemput1Laboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumLaboratory of Virology, Department of Translational Physiology, Infectiology and Public Health, Ghent University, Salisburylaan 133, 9820 Merelbeke, BelgiumBackground: Human herpesviruses are double-stranded DNA viruses of which eight types have been identified at present. Herpesvirus infection comprises an active lytic phase and a lifelong latency phase with the possibility of reactivation. These infections are highly prevalent worldwide and can lead to a broad spectrum of clinical manifestations, ranging from mild symptoms to severe disease, particularly in immunocompromised individuals. Clustered regularly interspaced palindromic repeats (CRISPR)-based therapy is an interesting alternative to current antiviral drugs, which fail to cure latent infections and are increasingly challenged by viral resistance. Objective: This scoping review aimed to summarize the current state of CRISPR-based antiviral strategies against herpesvirus infections, highlighting the underlying mechanisms, study design and outcomes, and challenges for clinical implementation. Design: A literature search was conducted in the databases PubMed and Web of Science, using both a general and an individual approach for each herpesvirus. Results: This scoping review identified five main mechanisms of CRISPR-based antiviral therapy against herpesvirus infections in vitro and/or in vivo. First, CRISPR systems can inhibit the active lytic replication cycle upon targeting viral lytic genes or host genes. Second, CRISPR technologies can remove latent viral genomes from infected cells by targeting viral genes essential for latency maintenance or destabilizing the viral genome. Third, reactivation of multiple latent herpesvirus infections can be inhibited by CRISPR-Cas-mediated editing of lytic viral genes, preventing a flare-up of clinical symptoms and reducing the risk of viral transmission. Fourth, CRISPR systems can purposefully induce viral reactivation to enhance recognition by the host immune system or improve the efficacy of existing antiviral therapies. Fifth, CRISPR technology can be applied to develop or enhance the efficiency of cellular immunotherapy. Conclusions: Multiple studies demonstrate the potential of CRISPR-based antiviral strategies to target herpesvirus infections through various mechanisms in vitro and in vivo. However, aspects regarding the delivery and biosafety of CRISPR systems, along with the time window for treatment, require further investigation before broad clinical implementation can be realized.https://www.mdpi.com/2076-0817/14/7/654CRISPR-Casherpesvirusantiviral therapygene therapy
spellingShingle Chloë Hanssens
Jolien Van Cleemput
Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
Pathogens
CRISPR-Cas
herpesvirus
antiviral therapy
gene therapy
title Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
title_full Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
title_fullStr Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
title_full_unstemmed Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
title_short Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review
title_sort applying crispr technologies for the treatment of human herpesvirus infections a scoping review
topic CRISPR-Cas
herpesvirus
antiviral therapy
gene therapy
url https://www.mdpi.com/2076-0817/14/7/654
work_keys_str_mv AT chloehanssens applyingcrisprtechnologiesforthetreatmentofhumanherpesvirusinfectionsascopingreview
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