Abstract
Even though chemotherapy and immunotherapy emerged to limit continual and unregulated proliferation of cancer cells, currently available therapeutic agents are associated with high toxicity levels and low success rates. Additionally, ongoing multi-targeted therapies are limited only for few carcinogenesis pathways, due to continually emerging and evolving mutations of proto-oncogenes and tumor-suppressive genes. CRISPR/Cas9, as a specific gene-editing tool, is used to correct causative mutations with minimal toxicity, but is also employed as an adjuvant to immunotherapy to achieve a more robust immunological response. Some of the most critical limitations of the CRISPR/Cas9 technology include off-target mutations, resulting in nonspecific restrictions of DNA upstream of the Protospacer Adjacent Motifs (PAM), ethical agreements, and the lack of a scientific consensus aiming at risk evaluation. Currently, CRISPR/Cas9 is tested on animal models to enhance genome editing specificity and induce a stronger anti-tumor response. Moreover, ongoing clinical trials use the CRISPR/Cas9 system in immune cells to modify genomes in a target-specific manner. Recently, error-free in vitro systems have been engineered to overcome limitations of this gene-editing system. The aim of the article is to present the knowledge concerning the use of CRISPR Cas9 technique in targeting treatment-resistant cancers. Additionally, the use of CRISPR/Cas9 is aided as an emerging supplementation of immunotherapy, currently used in experimental oncology. Demonstrating further, applications and advances of the CRISPR/Cas9 technique are presented in animal models and human clinical trials. Concluding, an overview of the limitations of the gene-editing tool is proffered.
Highlights
Cancer represents the second leading cause of deaths worldwide after cardiovascular diseases [1]
All of these results indicate Chimeric Antigen Receptors (CARs)-Ts as a potentially effective vector of anti-cancer treatment, with a growing amount of research focused on its application (Table 2)
CRISPR is favored over other genome editing tools due to its price but, most importantly, specificity and simplicity in designing gRNA to match specific targets
Summary
Cancer represents the second leading cause of deaths worldwide after cardiovascular diseases [1]. There is a large potential in recreating human disease in animal models, as well as in vitro modeling of genetic variants in CRISPR/Cas9-edited cell lines, possibly allowing to develop the fields of gene therapy and regenerative medicine [21]. CRISPR/Cas system is used to induce chromosomal abnormalities in vivo due to the possibility that the system offers to engineer short portions of DNA, but most importantly, large fragments in animal models [35] All of these examples support the effectiveness of the CRISPR/Cas system in both disease modelling in animal and in vitro studies and its applicational potential in the field of gene therapy.
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