A systematic review on the effect of human genomic variation on the effectivity of the CRISPR-Cas system in neurodegenerative disorders

Looyeh, Farhood Yoosefi (2021) A systematic review on the effect of human genomic variation on the effectivity of the CRISPR-Cas system in neurodegenerative disorders. [Project Paper] (Submitted)

Text FPSK2 2021 3.pdf Download (1MB)

Abstract

Introduction: Neurodegenerative diseases such as Alzheimer’s and Huntington’s are crippling and progressive diseases which directly affect the nervous system and result in the continuous death and impairment of neurons. Gene therapy hopes to shed some light on the future of effective treatment for such diseases. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has become a widely studied technique of genetic modification by permanently removing and correcting selected mutations on the DNA sequence. Objective: Thus, this review aimed at elucidating the current scientific evidence on the challenges of overcoming the target specificity of the CRISPR/Cas system caused by genetic polymorphism in neurodegenerative diseases. Methodology: Three databases namely PubMed, SCOPUS, and Science Direct were systematically searched for studies investigating the effect of genomic variation on the effectivity of CRISPR/Cas gene editing on neurodegenerative diseases. All studies that met the following criteria were included in the review: 1. Published and peer-reviewed research papers with detailed methodology and research objective; 2. Studies that feature at least one neurodegenerative disease; 3. Studies the use of CRISPR/Cas gene editing tool in gene therapy of neurodegenerative diseases; 4. Studies the relationship of genetic variation and effectivity of CRISPR/Cas therapy. Results: A total of 1008 articles included 114 from PubMed, 168 from SCOPUS, and 726 from Science Direct was collected. After removing duplicates, 895 articles were screened against the inclusion and exclusion criteria, leaving a total of 184 articles to undergo full-text screening. Only 39 out of the 184 articles were eligible to be included in the systematic review. Discussion: This review provides a comprehensive summary on the pre-clinical studies investigating the therapeutic potentials and the challenges imposed by genetic variation in CRISPR/Cas therapy. Genetic variations such as SNPs and indels were found to significantly reduce the on-target specificity of CRISPR/Cas editing at the target loci. Furthermore, population-specific variations in the therapeutically targeted loci were found to further complicate the editing of the gene using CRISPR/Cas technology. Moreover, out of the 39 articles, 15 of them reported various methods of editing the DMD gene in different disease models. Therefore, it can be assumed based on the current trend that treatment of Duchenne’s Muscular Dystrophy (DMD) using CRISPR/Cas gene editing will be the first to enter clinical phase. Conclusion: In summary, this study revealed that genetic variation does influence the on-target specificity of CRISPR/Cas gene therapy in neurodegenerative diseases. Hence, in order to enhance the ability of precise on-target gene editing by CRISPR/Cas, there is a necessity to improve the design of the delivery tools used such as guide RNAs. More studies must be done to further increase the validity and reliability of the results due to the novelty of CRISPR/Cas therapy in neurodegenerative diseases.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	21 Feb 2023 03:16
Last Modified:	21 Feb 2023 03:16
URI:	http://psaspb.upm.edu.my/id/eprint/752

Actions (login required)

View Item