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Updated: Nov 21, 2025
Mouse Genome Engineering Using Designer Nucleases
Published on: April 2, 2014
Designer nucleases to treat malignant cancers driven by viral oncogenes
Tristan A Scott1, Kevin V Morris2
1Center for Gene Therapy, City of Hope, Beckman Research Institute and Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA. trscott@coh.org.
Abstract:
Viral oncogenic transformation of healthy cells into a malignant state is a well-established phenomenon but took decades from the discovery of tumor-associated viruses to their accepted and established roles in oncogenesis. Viruses cause ~ 15% of know cancers and represents a significant global health burden. Beyond simply causing cellular transformation into a malignant form, a number of these cancers are augmented by a subset of viral factors that significantly enhance the tumor phenotype and, in some cases, are locked in a state of oncogenic addiction, and substantial research has elucidated the mechanisms in these cancers providing a rationale for targeted inactivation of the viral components as a treatment strategy. In many of these virus-associated cancers, the prognosis remains extremely poor, and novel drug approaches are urgently needed. Unlike non-specific small-molecule drug screens or the broad-acting toxic effects of chemo- and radiation therapy, the age of designer nucleases permits a rational approach to inactivating disease-causing targets, allowing for permanent inactivation of viral elements to inhibit tumorigenesis with growing evidence to support their efficacy in this role. Although many challenges remain for the clinical application of designer nucleases towards viral oncogenes; the uniqueness and clear molecular mechanism of these targets, combined with the distinct advantages of specific and permanent inactivation by nucleases, argues for their development as next-generation treatments for this aggressive group of cancers.
Insights
Viruses cause approximately 15% of cancers, and novel designer nuclease therapies offer a targeted approach to permanently inactivate viral oncogenes. This strategy holds promise for treating aggressive virus-associated cancers where current treatments are insufficient.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Viruses are responsible for approximately 15% of human cancers, posing a significant global health challenge.
- Certain viral factors enhance tumor progression and can lead to oncogenic addiction, necessitating targeted treatment strategies.
- Existing treatments like chemotherapy and radiation lack specificity and have limited efficacy in many virus-associated cancers.
Purpose of the Study:
- To explore the potential of designer nucleases as a novel therapeutic strategy for virus-associated cancers.
- To highlight the advantages of targeted inactivation of viral oncogenes over traditional cancer therapies.
Main Methods:
- Review of existing research on viral oncogenesis and the mechanisms of tumor-associated viruses.
- Analysis of the application of designer nuclease technology for targeting viral DNA.
- Evaluation of the potential for permanent inactivation of viral elements contributing to cancer.
Main Results:
- Designer nucleases offer a rational and specific approach to inactivate disease-causing viral targets.
- Permanent inactivation of viral oncogenes by nucleases can inhibit tumorigenesis.
- Evidence suggests the efficacy of designer nucleases in targeting viral elements within cancer cells.
Conclusions:
- Designer nucleases represent a promising next-generation treatment for aggressive virus-associated cancers.
- The unique molecular targets and specific inactivation mechanisms of nucleases offer distinct advantages.
- Further development is needed for clinical application, but the potential for permanent viral inactivation warrants continued research.
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