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By Tungki Pratama Umar, 2024

Enhanced Application of CRISPR-Cas13a for Cancer Gene Therapy

Introduction 

The invention of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)  technology, a revolutionary molecular instrument that allows for exquisite gene manipulation,  has radically transformed the field of molecular biology. It is a miracle of genetic engineering  that relies on the CRISPR-associated (Cas) proteins to function. Additionally, it provides  prospective therapeutic implications for various clinical demands, including non-infectious  diseases like cancer and infectious diseases like COVID-19. Another intriguing area of research is the integration of CRISPR with other technologies such as artificial  intelligence (AI). The implications of CRISPR are therefore significant, and this article will explore the applications of CRISPR,  specifically CRISPR-Cas13 in combination with AI to enhance cancer gene therapy. 

Cancer Gene Therapy and the Role of CRISPR 

Gene therapy is a significant medical advancement, particularly in cancer treatment options.  However, there are several challenges associated with the effective delivery of the therapy to the targeted cell, despite the availability of various genetic modification techniques such as gene silence, antisense treatment, RNA interference, and gene editing (Roma-Rodrigues et al., 2020).  

With its ability to target RNA, CRISPR-Cas13a has excellent potential for cancer gene  therapy. Cas13a disrupts gene expression in cancer cells by targeting RNA sequences associated with malignancy, albeit causing minor damage to healthy tissue. It is a remarkable  substitute for Cas9, which directly targets DNA. The transition from manipulating DNA to RNA creates new opportunities for precise and controlled genetic expression. Cas13a concentrates  on RNA-specific applications, reduces off-target effects, and improves specificity. Meanwhile,  Cas9 may be responsible for off-target DNA editing and irreversible genomic changes;  therefore, Cas13 provides a safer way to modify genes (Rao, 2021). 

According to a study, the novel Cas13a expression vector which used the decoy minimal  promoter-Cas13a-U6-guide RNA (DMP-Cas13a-U6-gRNA [DCUg]) was shown to reduce the  expression of endogenous oncogenes efficiently. This occurred specifically at both the mRNA and protein  levels in addition to reducing the expression of reporter genes in the human hepatoma cells 293T and HepG2. Additionally, it resulted in considerable reduction of the growth of hepatoma cells as well as apoptosis of these malignant cells with no impact on normal human liver cells (Gao et al., 2020). 

CRISPR-Cas13a and AI for Cancer Gene Therapy  

Genome editing has been revolutionised through the combination of AI and CRISPR-Cas13a. AI maximises the precision and efficiency of genome editing due to its capacity to analyse enormous datasets and spot intricate patterns. AI algorithms collaborate to discover the best sites for CRISPR-Cas13a by examining genomic data and locating specific RNA sequences linked to the targeted genetic abnormalities, enabling researchers to anticipate and evaluate the effects of CRISPR-Cas13a treatments prior to implementation. Furthermore, researchers can make well-informed decisions regarding the specificity of genetic modifications due to these predictive capabilities. This accuracy is revolutionary for genome editing, primarily focused therapies like cancer gene therapy.

Promising Results and Challenges 

Researchers have shown that disrupting cancer-related RNA sequences with  CRISPR-Cas13a in conjunction with AI effectively stops the growth of tumours in preclinical  models. Using this molecular scalpel, researchers may examine genetic abnormalities linked  to cancer. Delivering the RNA to the intended cells, reducing off-target effects, and handling  ethical issues in human trials are among the hurdles that still need to be overcome. Off-target  effects are reduced by Cas13a's accuracy and AI's predictive power, but they are still a cause  for concern. The objective is to balance prospective advantages, safety, and ethical aspects. 

Conclusion 

The combination of AI and CRISPR-Cas13a in cancer gene therapy is an ambitious endeavour that presents hope for improved cancer outcomes. With the use of AI and CRISPR-Cas13a's molecular precision as well as AI's computational power, cancer treatments may be administered with unprecedented precision and adaptability in the future. 

References 

Gao, J. et al. (2020) ‘A New Tool for CRISPR-Cas13a-Based Cancer Gene Therapy’,  Molecular Therapy - Oncolytics, 19, pp. 79–92. Available at:  https://doi.org/10.1016/j.omto.2020.09.004. 

 

Rao, K. (2021) ‘CRISPR-Cas13 and its Applications in Human Therapeutics’, Journal of High  School Science, 5(4), pp. 1–21. 

 

Roma-Rodrigues, C. et al. (2020) ‘Gene Therapy in Cancer Treatment: Why Go Nano?’,  Pharmaceutics, 12(3), p. 233.

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