Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 294-305 http://medscipublisher.com/index.php/cge 300 Figure 2 MMEJisauniqueDSBrepairpathwaythat results in highly efficient and highly stereotyped mutagenesis (Adopted from Ata et al., 2018) 5.2 Ethical Considerations in Human Germline and Somatic Gene Editing for Ovarian Cancer Gene editing for therapeutic purposes raises substantial ethical concerns, particularly when it involves editing the human germline. Germline gene editing, which can pass genetic changes to future generations, is controversial due to the potential for unintended long-term effects and the possibility of enhancing traits beyond disease prevention. In the context of ovarian cancer, where germline mutations in genes like BRCA1 and BRCA2 play a role in disease predisposition, the ethical implications of editing these mutations in embryos are profound. On the other hand, somatic gene editing, which targets non-reproductive cells, is seen as less ethically fraught but still presents challenges related to patient consent, access, and potential unintended consequences in tissues other than the tumor. Studies exploring the reversion of BRCA mutations via gene editing have highlighted the potential for therapeutic success but also raised ethical questions about long-term safety and the societal impacts of such interventions (Vidula et al., 2020). 5.3 Obstacles in Delivering Gene Editing Tools to Ovarian Tumor Tissues A major limitation in the application of gene editing technologies for ovarian cancer is the challenge of delivering the editing tools, such as CRISPR-Cas9, specifically to ovarian tumor tissues. Effective delivery requires overcoming biological barriers, such as the tumor microenvironment, immune surveillance, and potential degradation of the editing components before reaching the target cells. Researchers have developed various delivery systems, including lipid nanoparticles and viral vectors, to improve the targeting and uptake of gene editing tools by ovarian cancer cells. For instance, folate receptor-targeted liposomes have been employed to deliver CRISPR-Cas9 components into ovarian cancer cells with some success, as demonstrated in the suppression of the DNMT1 gene (He et al., 2018). However, delivering gene editing tools in vivo remains an obstacle, as off-target delivery can lead to unwanted side effects, and certain tumors may be resistant to uptake due to their heterogeneous nature or protective microenvironment.
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