Institute of Industrial Biotechnology, GC University, Lahore-54000, Pakistan.
Protein Pept Lett. 2020;27(10):931-944. doi: 10.2174/0929866527666200407112432.
Cancer is one of the most leading causes of mortality all over the world and remains a foremost social and economic burden. Mutations in the genome of individuals are taking place more frequently due to the excessive progress of xenobiotics and industrialization in the present world. With the progress in the field of molecular biology, it is possible to alter the genome and to observe the functional changes derived from genetic modulation using gene-editing technologies. Several therapies have been applied for the treatment of malignancy which affect the normal body cells; however, more effort is required to develop vsome latest therapeutic approaches for cancer biology and oncology exploiting these molecular biology advances. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated protein 9 (Cas9) system has emerged as a powerful technology for cancer therapy because of its great accuracy and efficiency. Genome editing technologies have demonstrated a plethora of benefits to the biological sciences. CRISPR- Cas9, a versatile gene editing tool, has become a robust strategy for making alterations to the genome of organisms and a potent weapon in the arsenal of tumor treatment. It has revealed an excellent clinical potential for cancer therapy by discovering novel targets and has provided the researchers with the perception about how tumors respond to drug therapy. Stern efforts are in progress to enhance its efficiency of sequence specific targeting and consequently repressing offtarget effects. CRISPR-Cas9 uses specific proteins to convalesce mutations at genetic level. In CRISPR-Cas9 system, RNA-guided Cas9 endonuclease harnesses gene mutation, DNA deletion or insertion, transcriptional activation or repression, multiplex targeting only by manipulating 20-nucleotide components of RNA. Originally, CRISPR-Cas9 system was used by bacteria for their defense against different bacteriophages, and recently this system is receiving noteworthy appreciation due to its emerging role in the treatment of genetic disorders and carcinogenesis. CRISPR-Cas9 can be employed to promptly engineer oncolytic viruses and immune cells for cancer therapeutic applications. More notably, it has the ability to precisely edit genes not only in model organisms but also in human being that permits its use in therapeutic analysis. It also plays a significant role in the development of complete genomic libraries for cancer patients. In this review, we have highlighted the involvement of CRISPR-Cas9 system in cancer therapy accompanied by its prospective applications in various types of malignancy and cancer biology. In addition, some other conspicuous functions of this unique system have also been discussed beyond genome editing.
癌症是全球主要的死亡原因之一,仍然是首要的社会和经济负担。由于当今世界外来物质和工业化的过度发展,个体基因组中的突变越来越频繁。随着分子生物学领域的进步,利用基因编辑技术改变基因组并观察遗传修饰带来的功能变化成为可能。已经有几种治疗方法应用于治疗影响正常体细胞的恶性肿瘤;然而,为了开发利用这些分子生物学进展的最新癌症生物学和肿瘤学治疗方法,还需要付出更多的努力。最近,簇状规律间隔短回文重复序列(CRISPR)相关蛋白 9(Cas9)系统已成为癌症治疗的一种强大技术,因为其具有高度的准确性和效率。基因组编辑技术为生物科学带来了诸多益处。CRISPR-Cas9 是一种多功能的基因编辑工具,已成为改变生物体基因组的有效策略,也是肿瘤治疗的有力武器。它通过发现新的靶点为癌症治疗带来了极好的临床潜力,并为研究人员提供了关于肿瘤对药物治疗反应的认识。目前正在努力提高其序列特异性靶向的效率,从而减少脱靶效应。CRISPR-Cas9 使用特定的蛋白质在基因水平上修复突变。在 CRISPR-Cas9 系统中,RNA 引导的 Cas9 内切酶利用基因突变、DNA 缺失或插入、转录激活或抑制、仅通过操纵 RNA 的 20 个核苷酸成分进行多重靶向。最初,CRISPR-Cas9 系统被细菌用于防御不同的噬菌体,最近由于其在治疗遗传疾病和致癌作用方面的新兴作用,该系统受到了广泛关注。CRISPR-Cas9 可用于快速设计溶瘤病毒和免疫细胞,用于癌症治疗应用。更值得注意的是,它不仅可以精确编辑模型生物中的基因,还可以编辑人类基因,这使其可用于治疗分析。它在癌症患者的全基因组文库的开发中也发挥着重要作用。在这篇综述中,我们强调了 CRISPR-Cas9 系统在癌症治疗中的作用,并探讨了其在各种类型恶性肿瘤和癌症生物学中的潜在应用。此外,我们还讨论了该系统除了基因组编辑之外的一些其他显著功能。