Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 294-305 http://medscipublisher.com/index.php/cge 296 require extremely high precision and are still considered a valuable tool in therapeutic gene editing, especially for diseases caused by specific gene mutations. The main limitation of ZFNs is their potential for off-target effects and the complexity involved in designing the zinc finger proteins, but ongoing improvements aim to address these challenges. 2.4 Emerging techniques: base editing and prime editing Base editing and prime editing are two groundbreaking advancements in gene editing that allow more precise modifications than CRISPR-Cas9 without causing double-strand breaks. Base editors use an engineered deaminase to convert specific nucleotides (such as cytosine to thymine or adenine to guanine), providing a tool for correcting point mutations. This technique is especially useful in diseases where single nucleotide changes are responsible, as seen in some types of cancer (Vasquez et al., 2020). Prime editing, a newer innovation, builds on CRISPR technology by incorporating a reverse transcriptase that can directly rewrite sections of DNA without needing a donor template or DSBs. This provides even greater control over genetic changes, making it ideal for correcting more complex mutations. In cancer research, base and prime editing hold promise for treating genetic mutations with higher accuracy and fewer risks compared to traditional CRISPR-Cas9 methods (Schreurs et al., 2021). These tools are particularly relevant in developing therapies for cancers driven by single nucleotide polymorphisms (SNPs) or other precise genetic alterations. While still in their early stages, base and prime editing are expected to revolutionize gene therapy, offering safer and more efficient ways to treat cancer and other genetic diseases. 3 Current Gene Editing Research in Ovarian Cancer 3.1 Identification of key oncogenes and tumor suppressors Gene editing technologies have dramatically enhanced our understanding of ovarian cancer’s genetic landscape, particularly in identifying key oncogenes and tumor suppressors, driving mechanisms of tumor growth and metastasis, and studying drug resistance. Tools like CRISPR-Cas9, TALENs, and RNA interference (RNAi) have been instrumental in this research, allowing scientists to explore genetic modifications in ovarian cancer models and uncovering new therapeutic targets. Gene editing has been pivotal in identifying oncogenes and tumor suppressor genes central to ovarian cancer progression. Oncogenes like FOXM1, ERBB2, and CCNE1 have been studied extensively using CRISPR-Cas9 and RNA interference techniques to reveal their role in cancer proliferation and chemoresistance. For instance, CRISPR-based knockdown of FOXM1 in ovarian cancer cell lines revealed that its suppression not only inhibits tumor growth but also increases sensitivity to platinum-based chemotherapy. FOXM1 is frequently overexpressed in high-grade serous ovarian cancer and is strongly associated with poor prognosis, making it a promising target for gene-based therapies (Tassi et al., 2017). Similarly, studies have revealed the importance of tumor suppressor genes like BRCA1, TP53, and OPCML in ovarian cancer. For example, research has shown that the tumor suppressor gene OPCML can sensitize ovarian cancer cells to platinum drugs and targeted therapies against EGFR/HER2 (Zanini et al., 2017). The identification and functional validation of these oncogenes and tumor suppressors through gene editing have significantly improved our understanding of ovarian cancer biology and treatment. 3.2 Studies on gene-driven tumor growth and metastasis Gene editing technologies have also enabled detailed studies on the genetic drivers of tumor growth and metastasis in ovarian cancer. Research has shown that RhoC, a gene implicated in cancer stem cell regulation, plays a critical role in promoting tumorigenesis, metastasis, and chemoresistance in ovarian cancer. CRISPR-Cas9 and RNA interference techniques used to downregulate RhoC expression in ovarian cancer stem cells significantly suppressed their proliferation, drug resistance, and invasion capabilities (Sang et al., 2016). Other studies have focused on understanding the metastatic potential of ovarian cancer through the identification of genes like TXN and RAD51C, which are associated with enhanced cell adhesion and invasion. In one genome-wide screen using shRNA libraries, knockdown of these genes in ovarian cancer cells led to increased metastatic potential in experimental models, providing critical insights into the molecular pathways driving metastasis (Kodama et al., 2016).
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