Abstract
Cancer is one of the most leading causes of mortalities worldwide. It is caused by the accumulation of genetic and epigenetic alterations in 2 types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. In recent years, development of the clustered regularly interspaced short palindromic repeats (CRISPR) technology has revolutionized genome engineering for different cancer research ranging for research ranging from fundamental science to translational medicine and precise cancer treatment. The CRISPR/CRISPR associated proteins (CRISPR/Cas) are prokaryote-derived genome editing systems that have enabled researchers to detect, image, manipulate and annotate specific DNA and RNA sequences in various types of living cells. The CRISPR/Cas systems have significant contributions to discovery of proto-oncogenes and TSGs, tumor cell epigenome normalization, targeted delivery, identification of drug resistance mechanisms, development of high-throughput genetic screening, tumor models establishment, and cancer immunotherapy and gene therapy in clinics. Robust technical improvements in CRISPR/Cas systems have shown a considerable degree of efficacy, specificity, and flexibility to target the specific locus in the genome for the desired applications. Recent developments in CRISPRs technology offers a significant hope of medical cure against cancer and other deadly diseases. Despite significant improvements in this field, several technical challenges need to be addressed, such as off-target activity, insufficient indel or low homology-directed repair (HDR) efficiency, in vivo delivery of the Cas system components, and immune responses. This study aims to overview the recent technological advancements, preclinical and perspectives on clinical applications of CRISPR along with their advantages and limitations. Moreover, the potential applications of CRISPR/Cas in precise cancer tumor research, genetic, and other precise cancer treatments discussed.
Highlights
Cancer is one of the main causes of disease-associated mortalities worldwide with ever-increasing incidence worldwide [1]
clustered regularly interspaced short palindromic repeats (CRISPR) is a promising tool that has been widely adopted in oncology research (Figure 2) with focusing on; animal tumor model construction, the discovery of new drug targets; cancer gene therapy, genetic screening related to drug resistance, and many others
The production of chimeric antigen receptor T (CAR-T) cells are significantly associated with the cancer therapy
Summary
Cancer is one of the main causes of disease-associated mortalities worldwide with ever-increasing incidence worldwide [1]. The first generation genome editing strategies in mammalian cells have been utilized the plasmid based expression of Cas and sgRNA [8, 9] This approach is efficient for in vivo applications in model organisms such as mice because the plasmid can be delivered to the tissue by hydrodynamic injection [67] or electroporation [68,69,70]. Different studies have recently developed a safe and effective strategy for antibody-targeted cell-specific delivery of mRNAs and siRNAs through systemically administration of LNPs [95,96,97] In this regard, few studies have reported promising outcomes in using LNPs for the delivery of Cas mRNA and sgRNAs. The initial findings showed that aminoionizable LNPs could serve as a safe and efficient carrier for Cas components [87]. The capacity of disrupting gene expression in vivo in tumors is a promising feature for translating CRISPR tools into clinical applications and paves the way for developing gene editing techniques for cancer research and treatment and potential applications for targeted gene editing of non-malignant tissues
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