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CRISPR-Cas9 as a Powerful Tool for Efficient Creation of Oncolytic Viruses
Ming Yuan1, Eika Webb2, Nicholas Robert Lemoine3,4
1Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK. m.yuan@qmul.ac.uk.
Abstract:
The development of oncolytic viruses has led to an emerging new class of cancer therapeutics. Although the safety profile has been encouraging, the transition of oncolytic viruses to the clinical setting has been a slow process due to modifications. Therefore, a new generation of more potent oncolytic viruses needs to be exploited, following our better understanding of the complex interactions between the tumor, its microenvironment, the virus, and the host immune response. The conventional method for creation of tumor-targeted oncolytic viruses is based on homologous recombination. However, the creation of new mutant oncolytic viruses with large genomes remains a challenge due to the multi-step process and low efficiency of homologous recombination. The CRISPR-associated endonuclease Cas9 has hugely advanced the potential to edit the genomes of various organisms due to the ability of Cas9 to target a specific genomic site by a single guide RNA. In this review, we discuss the CRISPR-Cas9 system as an efficient viral editing method for the creation of new oncolytic viruses, as well as its potential future applications in the development of oncolytic viruses. Further, this review discusses the potential of off-target effects as well as CRISPR-Cas9 as a tool for basic research into viral biology.
Insights
The CRISPR-Cas9 system offers an efficient method for editing viral genomes to create novel oncolytic viruses for cancer therapy. This advanced gene-editing tool overcomes limitations of traditional methods, accelerating the development of potent cancer treatments.
Area of Science:
- Oncolytic virotherapy
- Gene editing technologies
- Cancer therapeutics development
Background:
- Oncolytic viruses represent a promising class of cancer therapeutics with a favorable safety profile.
- Clinical translation of oncolytic viruses is hindered by complex modifications and limitations in creating potent viral strains.
- Understanding tumor-virus-host interactions is crucial for developing next-generation oncolytic viruses.
Purpose of the Study:
- To review the CRISPR-Cas9 system as an efficient method for editing viral genomes.
- To discuss the application of CRISPR-Cas9 in creating novel oncolytic viruses.
- To explore future applications and potential challenges of CRISPR-Cas9 in oncolytic virus development.
Main Methods:
- Review of existing literature on CRISPR-Cas9 gene editing.
- Analysis of CRISPR-Cas9's application in viral genome modification.
- Discussion of homologous recombination limitations in oncolytic virus engineering.
Main Results:
- CRISPR-Cas9 enables precise and efficient editing of viral genomes, surpassing traditional methods like homologous recombination.
- This system facilitates the creation of engineered oncolytic viruses with enhanced tumor-targeting capabilities and potency.
- CRISPR-Cas9 also serves as a valuable tool for fundamental research in viral biology.
Conclusions:
- The CRISPR-Cas9 system is a transformative technology for developing advanced oncolytic viruses.
- It addresses key challenges in engineering potent and targeted oncolytic agents for cancer therapy.
- Further research into CRISPR-Cas9 applications and safety is warranted for its clinical integration.
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