International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 193-202 http://medscipublisher.com/index.php/ijmms 199 economic disparities that exist in healthcare systems globally. Additionally, the infrastructure needed to support gene therapy, including specialized facilities and trained personnel, is not universally available, further exacerbating access issues (Romero et al., 2018). 6.4 Regulatory and safety evaluations Regulatory and safety evaluations are critical to the successful implementation of gene editing technologies. Ensuring that edited cells do not cause adverse effects, such as insertional mutagenesis or off-target gene disruptions, is paramount (DeWitt et al., 2016; Lin et al., 2017). Comprehensive in vivo safety and toxicology studies are necessary to evaluate the long-term effects of gene editing (Ebens et al., 2019). Regulatory bodies must establish clear guidelines and robust monitoring systems to oversee the clinical application of these therapies, ensuring that they meet stringent safety and efficacy standards (Urnov, 2017). While gene editing technologies hold great promise for treating sickle cell anemia, addressing the technical, ethical, socioeconomic, and regulatory challenges is essential for their successful and equitable implementation. Continued research and collaboration among scientists, ethicists, policymakers, and healthcare providers are crucial to overcoming these barriers and realizing the full potential of gene editing in curing SCA. 7 Future Perspectives 7.1 Technological advancements The future of gene editing technologies in treating sickle cell anemia (SCA) is promising, with several advancements on the horizon. CRISPR/Cas9 has shown high efficiency in editing human primary hematopoietic stem and progenitor cells (HSPCs) to upregulate fetal hemoglobin (HbF), which can ameliorate the symptoms of SCA (Lin et al., 2017; Frangoul et al., 2020). Additionally, base editing technologies, such as cytosine and adenine base editors, offer precise genome modifications without introducing double-strand breaks, which can further enhance the safety and efficacy of gene therapies (Lin et al., 2019; Zeng et al., 2020). These advancements are crucial for achieving high editing efficiencies and ensuring the long-term viability and functionality of edited cells (Lin et al., 2017; Zeng et al., 2020). 7.2 Combining therapies Combining gene editing with other therapeutic approaches holds significant potential for treating SCA. For instance, integrating gene editing with viral transduction techniques can enhance the overall therapeutic outcome by ensuring robust and sustained expression of therapeutic genes (Romero et al., 2018; Quintana-Bustamante et al., 2022). Moreover, the combination of base editing and CRISPR/Cas9 technologies can target multiple genetic loci simultaneously, thereby increasing the therapeutic efficacy and reducing the disease burden in patients (Lin et al., 2019; Zeng et al., 2020). This multi-faceted approach can address the limitations of single-modality treatments and provide a more comprehensive solution for SCA (Hossain and Bungert, 2017; Romero et al., 2018). 7.3 Long-term vision The long-term vision for gene editing in SCA involves not only curing the disease but also ensuring the accessibility and affordability of these therapies. As gene editing technologies advance, it is essential to optimize the delivery methods, improve the specificity and efficiency of gene modifications, and ensure the safety of edited cells (Hossain and Bungert, 2017). Additionally, addressing the challenges of implementing these therapies in regions where SCA is endemic is crucial for making these treatments universally available (Romero et al., 2018). Ultimately, the goal is to develop a universal curative option for SCA that can be safely and effectively administered to all patients, regardless of their geographic or socioeconomic status (Romero et al., 2018). 8 Concluding Remarks Gene editing technologies have shown significant promise in the treatment of sickle cell anemia (SCA). Various approaches, including CRISPR/Cas9, base editing, and gene addition/editing, have demonstrated the potential to correct the genetic mutation responsible for SCA or to induce the expression of fetal hemoglobin (HbF) to compensate for defective adult hemoglobin. Studies have reported successful ex vivo editing of hematopoietic stem/progenitor cells (HSPCs) and their subsequent engraftment in animal models, leading to reduced sickling of red blood cells and improved hematological parameters.
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