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Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
Genome Editing Technologies for Cancer Therapy
Gautham Chengizkhan1,2, Arumugam Rajavelu3, Sridhar Muthusami4,5
1Departments of Otolaryngology - Head and Neck Surgery, The University of Oklahoma Health Sciences Center, 800 Research Parkway, Oklahoma City, OK 73104, USA.
Abstract:
Cancer remains one of the leading causes of death worldwide, and the limitations of conventional therapies such as surgery, chemotherapy, and radiotherapy underscore the urgent need for innovative therapeutic strategies. While advances in early detection and treatment have improved outcomes in some regions, challenges such as micrometastasis, tumor relapse, and multidrug resistance continue to hinder long-term success. The multifactorial nature of cancer-driven by complex genetic mutations, diverse tumor microenvironments, and adaptive cancer cell behavior- demands more precise and effective solutions. Recent breakthroughs in molecular biology and genetic engineering have led to the emergence of genome editing technologies that offer promising avenues for targeted cancer therapy. This review highlights the evolution and application of key genome editing platforms, including meganucleases, zinc finger nucleases (ZFNs), transcription activator- like effector nucleases (TALENs), and the CRISPR/CAS9 system. Meganucleases were among the earliest tools with site-specific cutting ability, but limited versatility. ZFNs and TALENs offered greater modularity and target specificity through protein-DNA interactions. The CRISPR/CAS9 system revolutionized genome editing with its RNA-guided targeting, allowing for higher efficiency, simplicity, and flexibility in gene modification. These tools have enabled researchers to disrupt oncogenes, repair tumor suppressor genes, and manipulate signalling pathways involved in tumor progression, resistance, and metastasis. Moreover, ongoing advancements in delivery systems and gene repair mechanisms have further enhanced their therapeutic potential. We also discuss their translational potential from bench to bedside and explore future perspectives on how these technologies may revolutionize precision oncology, ultimately contributing to more effective treatment outcomes.
Insights
Genome editing technologies like CRISPR/CAS9 offer new ways to fight cancer by precisely targeting genes. These advanced tools hold promise for developing more effective precision oncology treatments and improving patient outcomes.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Cancer is a leading global cause of death, with conventional therapies facing limitations like drug resistance and relapse.
- The complex nature of cancer necessitates innovative therapeutic strategies beyond traditional methods.
Purpose of the Study:
- To review the evolution and application of genome editing technologies for targeted cancer therapy.
- To highlight the potential of these tools in revolutionizing precision oncology.
Main Methods:
- Review of key genome editing platforms: meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/CAS9.
- Discussion of gene modification strategies including oncogene disruption and tumor suppressor gene repair.
Main Results:
- Genome editing tools have advanced from early meganucleases to highly efficient RNA-guided CRISPR/CAS9 systems.
- These technologies enable precise manipulation of genes involved in cancer progression, resistance, and metastasis.
Conclusions:
- Genome editing technologies show significant translational potential for cancer treatment.
- Advancements in delivery systems and gene repair enhance therapeutic prospects, paving the way for precision oncology.
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