International Journal of Molecular Medical Science, 2024, Vol.14, No.1, 1-7 http://medscipublisher.com/index.php/ijmms 2 their advantages and current challenges. This review paper can provide comprehensive understanding for researchers and clinical doctors, and point out the direction for future research and practice in the treatment of genetic diseases. 1 Application of Gene Editing in the Treatment of Hereditary Diseases 1.1 Definition of gene editing Gene editing refers to the technique of accurately modifying and adjusting the genome of an organism through deliberate human intervention. The main principle is to introduce specific nucleases or protein tools to interact with the target DNA sequence, achieving operations such as DNA mutation, insertion, or deletion. Among them, the most widely used gene editing technology is the CRISPR-Cas9 system. This system utilizes Cas9 protein binds to specific guiding RNA (gRNA) to form complexes for precise identification and binding of target DNA sequences, thereby triggering the process of genome editing. In addition to the CRISPR-Cas9 system, there are other gene editing techniques such as zinc finger nucleases (ZFNs) and deoxyribonucleases (TALENs) that can also achieve precise genome modifications. Different gene editing techniques differ in terms of target selection, editing efficiency, and specificity. 1.2 Application of gene editing in the treatment of genetic diseases 1.2.1 Application in the treatment of monogenic genetic diseases Monogenic genetic diseases, caused by mutations in a single gene, have found new hope in the application of gene editing technologies. The primary tool for gene editing is the CRISPR-Cas9 system, which allows precise modification of the genome to restore normal function. Gene editing can be employed to correct disease phenotypes by repairing mutated genes. This approach is applicable to specific types of mutations,, such as point mutations, insertions, and deletions. By introducing a repair template, gene editing can restore the normal sequence of genes and repair the functionality of disease-associated genes. For instance, in the context of cystic fibrosis, a common monogenic disease, gene editing techniques have been used to repair the CFTR gene. Researchers use the CRISPR-Cas9 system to precisely cleave the mutated gene sequence and introduce a normal repair template into cells through homologous recombination. This repair method has demonstrated feasibility and effectiveness in cell and animal models, providing a new avenue for gene therapy in cystic fibrosis.t. For gene mutations that cannot be repaired, gene editing technologies can facilitate gene replacement, which involves inserting normal gene sequences into damaged gene sites to restore their normal function. This method is applicable to certain monogenic genetic diseases, such as spinal muscular atrophy. For instance, some studies have utilized gene editing techniques to insert the normal SMN1 gene sequence into the genome of patients with spinal muscular atrophy. This gene replacement approach has been shown to increase the levels of SMN protein in patients, thereby improving the symptoms of the disease. Gene editing technology can also be employed for gene silencing, involving the precise cleavage and disruption of the sequence of detrimental genes to inhibit their function. This method is applicable to certain monogenic genetic diseases, such as fragile X syndrome. For example, fragile X syndrome is caused by an expansion mutation of the FMR1 gene on the X chromosome (Figure 1). In the treatment of fragile X syndrome, researchers have utilized the CRISPR-Cas9 system for gene silencing targeting the FMR1 gene (Liao et al., 2022). By accurately cleaving the sequence of this gene, the production of harmful proteins can be reduced, thereby alleviating the symptoms. 1.2.2 Application in the treatment of polygenic genetic diseases Gene editing technology has demonstrated significant potential in the treatment of polygenic genetic diseases. Polygenic genetic diseases are disorders caused by mutations in multiple genes, such as hereditary heart disease, chromosomal abnormality syndromes and so forth. Gene editing can be utilized to repair mutations in multiple genes, in order to restore the functionality of genes associated with polygenic genetic diseases. By introducing multiple repair templates, it is possible to simultaneously correct mutations in different genes. This approach can be applied in certain polygenic genetic diseases, such as hereditary heart disease (Zhang et al., 2020).
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