The Potential Revolution of Cancer Treatment with CRISPR-Cas9
The Potential Revolution of Cancer Treatment with CRISPR-Cas9
Mehrdad Ostadpoor,1,*Majid Gholami-Ahangaran,2Seyyed Hossein Heidari,3
1. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. 2. Associate Professor, Group of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran. 3. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Introduction: Cancer is one of the leading causes of disease-associated mortality with rising incidence worldwide. Simultaneously, advances have been made in the prevention and treatment of many types of cancer, which result in prolonged survival or even cures. Existing means in clinical treatment of cancer, including surgery, chemotherapy and radiotherapy, can cause certain effects. CRISPR/Cas9 is a prokaryotic, adaptive immune system that consists of a programmable RNA molecule that helps guide an associated Cas9 endonuclease to specific exogenous genetic invaders based on recognized sequences. Powerful genome-editing technology known as Clustered regularly interspaced palindromic sequences-acronym CRISPR, is now eclipsing all other genome-engineering techniques. This revolutionary technique allows researchers to accomplish targeted manipulation in any gene (DNA sequence) in the entire genome of any organism in vitro or now even directly in endogenous genome, thus helping to elucidate the functional organization of genome at systems level and identifying casual genetic variations.
Methods: In the current study, keywords including CRISPR-Cas9, Cancer, and Treatment were reviewed from the list of Mesh and other credible websites including PubMed, Science Direct and Google Scholar and the data was organized. The searches comprised all published paper from 2000 to 2022. All of full text was considered and the papers manifested as only abstract was excluded. The full papers selected that specific effect on cancers only. Totally 50 papers were selected and studied in this review.
Results: CRISPR plays a vital role in detection of cancers. The CRISPR-Cas9 system evolved as an immune defense against foreign bacteriophage or plasmid infection in bacteria or archaea. Genome editing by CRISPR-Cas9 system for production of the chimeric antigen receptor (CAR) has been broadly recognized as one of the largest progress in personalized cancer immunotherapy. A recent clinical trial 38 showed that autologous reintroduction of CD4T cells whose CCR5 (CC chemokine receptor 5) gene was inactivated in vitro by ZFN was safe and lead to decreased viral load, lending support to the potential of CRISPR-Cas9 in Acquired immunodeficiency syndrome (AIDS) gene therapy. Articles show CRISPR-Cas9 editing system is derived from bacterial native immune system and hence has inherent advantage in defense against or clearance of viral infection that are associated with carcinogenesis, such as HBV and hepatitis C virus in liver cancer, Epstein-Barr virus (EBV) in nasopharyngeal carcinoma and human papillomavirus (HPV) in cervical cancer. The primary CRISPR/Cas9 clinical trial in China is editing T cells from patients with CRISPR/Cas9 system in vitro and transplanting these altered cells back into the patients to upgrade the tumor treatment effect. Other articles demonstrated catalytically inactive dCas9 can be recruited by gRNAs to specific target DNA sites, and when fused to transcriptional activation or inhibition domains, can be exploited to activate or repress specific target genes. The approach is based on CRISPR/Cas9-mediated PD-1 gene deletion in T-cells ex vivo and their reintroduction into patients, where the gene-deleted T-cell will home to the tumor and activate the immune response with the possibility of tumor eradication.
Conclusion: In conclusion, the RNA-guided genome editing tool CRISPR-Cas9 offers several advantages over protein guided counterparts and RNAi techniques. It has shown therapeutic potentials in cell lines or animal models for infectious diseases, monogenic diseases and cancer so CRISPR plays a vital role in detection of cancers.