Abstract
Lung cancer (LC) is the most common cause of cancer-related death worldwide. Patients with LC are usually diagnosed at advanced phases. Five-year survival rate in LC patients is approximately 16%. Despite decades of research on LC treatments, clinical outcomes are still very poor, necessitating to develop novel technologies to manage the disease. Considering the role of genetic and epigenetic changes in oncogenes and tumor-suppressor genes in cancer progression, gene therapy provides a hot spot in cancer treatment research. Gene therapy offers less side effects compared to conventional methods such as chemotherapy. Unlike the traditional approaches of gene therapy that have temporary effects, using genetic modification tools can offer persistent cure. Over the past a few years, many studies have effectively used the CRISPR–Cas9 approach to modify gene expression in cells. This system is applied to induce site-specific mutagenesis and epigenetic modifications and regulate gene expression. In this review, we discuss recent applications of the CRISPR–Cas9 technology in treating LC.
Highlights
M advanced Lung cancer (LC) is approximately 16% while this reaches above 50% in those who are diagnosed at early phases
Adenocarcinoma is the most prevalent (70-80%) type of non-small-cell lung cancer (NSCLC) followed by large cell carcinoma
An important advantage of the clustered regularly interspaced short palindromic repeats (CRISPR) system is 2|Page that this system targets genomic sequences by a single-guide RNA instead of proteinbased detection used in Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) (Table 1)
Summary
M advanced LC is approximately 16% while this reaches above 50% in those who are diagnosed at early phases. These include using short sgRNAs, structure-guided designing of Cas[9], deactivating Cas[9] (dCas9) by FokI enzymes, applying programmable DNA-binding domains such as zinc-finger proteins or TALENs, and introducing chemical alterations to improve specific DNA binding affinity.[10,53,54] By exploiting several CRISPR activators (CRISPRa) or 7|Page inhibitors (CRISPRi), the CRISPR-Cas system can be employed to regulate gene expression.[55,56]
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