CRISPR/Cas Against Cancer-Associated Viruses: A Review of Preclinical Potential and Challenges
Background: Gene editing to target viral persistence
CRISPR/Cas approaches aimed at cancer-associated viruses have shown preclinical potential to disrupt targets involved in viral persistence and tumor development. A review published in Biomedicine & Pharmacotherapy summarizes the prospects for therapeutic development and the remaining challenges. It should be distinguished from a single experimental study reporting complete viral clearance or cancer treatment in patients.
The review covers cancer-associated viruses including human papillomavirus (HPV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Many of these viruses contribute to cancer by integrating into the host genome or persisting as chronic or latent infections. Persistent infection therefore cannot always be described as integration into host DNA. Human immunodeficiency virus (HIV) is also discussed, with the review distinguishing its possible indirect contribution to cancer through immune dysregulation.
Key findings: Differences between DNA targeting and RNA inhibition
The strategies summarized in the review include excision of viral DNA integrated into the host genome, interference with viral replication, suppression of viral transcripts, and modulation of host tumor-suppressor pathways. Even when based on CRISPR, these approaches differ in their targets and intended effects.
The abstract explains that Cas9 targets DNA viruses such as HBV and HPV, while RNA-targeting Cas13 may be used to suppress RNA viruses such as HCV. DNA excision and RNA inhibition cannot both be assumed to represent complete removal of the viral genome. The provided abstract also gives no numerical results directly comparing the effects of the two approaches.
Preclinical examples include disruption of HBV cccDNA; suppression of latency-associated gene expression in Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV); and the potential inactivation of oncogenes in human T-cell leukemia virus type 1 (HTLV-1). These are distinct targeting strategies intended to reduce viral persistence and tumor progression. However, the available abstract does not specify the models, treatment conditions, observation periods, or effect sizes of individual experiments, making it difficult to determine which strategy is superior.
Implications and outlook: Safety and delivery challenges in therapeutic development
The review’s value lies in bringing together virus-specific therapeutic targets and development challenges. Whether disruption of viral genetic material or gene expression leads to actual cancer prevention or treatment benefits requires separate verification. The abstract alone does not support claims about patient treatment responses, improved cure rates, or the effects of a single dose.
Remaining challenges include off-target effects at unintended sites, the delivery efficiency of editing tools, immune responses, and ethical concerns. The review identifies high-fidelity Cas variants, base editing and prime editing, and nonviral delivery systems as development directions for improving safety and therapeutic precision. This does not mean these technologies have already resolved the obstacles. Follow-up studies must assess safety and delivery performance alongside the effects of target disruption before the potential for clinical application can be evaluated.
Source: Review abstract and bibliographic record in Europe PMC.
CRISPR/Cas systems, initially characterized as bacterial adaptive immune mechanisms, have rapidly emerged as precise and versatile genome-editing tools with significant potential for antiviral research and therapeutic development. This review highlights the role of CRISPR/Cas systems in targeting persistent and human oncogenic viruses, including HPV, HBV, HCV, EBV, KSHV, HTLV-1, and MCPyV, as well as HIV, which may indirectly contribute to cancer through immune dysregulation. Many of these viruses can integrate into the host genome or persist as chronic or latent infections, contributing to cancers for which curative options are limited. CRISPR-based strategies enable the excision of integrated proviral DNA, disruption of viral replication, targeted silencing of viral transcripts, and modulation of host tumor-suppressor pathways. Cas9 efficiently targets DNA viruses, such as HBV and HPV, whereas RNA-targeting Cas13 allows precise silencing of RNA viruses, like HCV. Editing T-cell receptors, including CCR5 and CXCR4, offers the potential for long-term resistance to HIV. CRISPR-based preclinical studies indicate the potential to disrupt HBV cccDNA, suppress EBV and KSHV latency gene expression, and inactivate HTLV-1 oncogenes, thereby potentially reducing viral persistence and oncogenic progression. Despite these advances, challenges remain regarding off-target effects, delivery efficiency, immune responses, and ethical considerations. Innovations such as high-fidelity Cas variants, base and prime editing, and non-viral delivery systems are expected to enhance both safety and therapeutic precision. This review provides an overview of viral life cycles, oncogenic pathways, and therapeutic vulnerabilities of human oncogenic viruses and CRISPR-based genome-editing approaches under investigation for viral elimination and cancer therapy.
Research teams developing therapies against viruses can use this review as a starting point for examining virus-specific targeting strategies. For example, an approach aimed at HBV cccDNA and one that suppresses latency-associated gene expression involve different effects to be evaluated, so they cannot simply be grouped as equivalent viral clearance outcomes. When assessing candidate strategies, teams should consider delivery efficiency, off-target effects, and immune responses alongside effects on the target. The available abstract outlines research and development directions but does not provide a basis for comparing the performance of individual candidates or choosing a treatment for patients. Clinical value can be judged after testing whether the potential for viral suppression translates into actual therapeutic benefit.