Opinion Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 16, 2023; 11(14): 3114-3127
Published online May 16, 2023. doi: 10.12998/wjcc.v11.i14.3114
Modernising autism spectrum disorder model engineering and treatment via CRISPR-Cas9: A gene reprogramming approach
Arushi Sandhu, Anil Kumar, Kajal Rawat, Vipasha Gautam, Antika Sharma, Lekha Saha
Arushi Sandhu, Anil Kumar, Kajal Rawat, Vipasha Gautam, Antika Sharma, Lekha Saha, Department of Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 0172, Chandigarh, India
Author contributions: Sandhu A contributed to conceptualization, writing-original draft preparation, visualization and investigation, reviewing and editing; Kumar A, Rawat K and Sharma A wrote the original draft; Gautam V wrote the original draft and proofread; Saha L contributed to conceptualization, supervision, reviewing and editing.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lekha Saha, MBBS, MD, MNAMS, Full Professor, Professor, Department of Pharmacology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 0172, Chandigarh, India. lekhasaha@rediffmail.com
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: January 30, 2023
Revised: February 13, 2023
Accepted: April 6, 2023
Article in press: April 6, 2023
Published online: May 16, 2023
Processing time: 139 Days and 5 Hours
Abstract

A neurological abnormality called autism spectrum disorder (ASD) affects how a person perceives and interacts with others, leading to social interaction and communication issues. Limited and recurring behavioural patterns are another feature of the illness. Multiple mutations throughout development are the source of the neurodevelopmental disorder autism. However, a well-established model and perfect treatment for this spectrum disease has not been discovered. The rising era of the clustered regularly interspaced palindromic repeats (CRISPR)-associated protein 9 (Cas9) system can streamline the complexity underlying the pathogenesis of ASD. The CRISPR-Cas9 system is a powerful genetic engineering tool used to edit the genome at the targeted site in a precise manner. The major hurdle in studying ASD is the lack of appropriate animal models presenting the complex symptoms of ASD. Therefore, CRISPR-Cas9 is being used worldwide to mimic the ASD-like pathology in various systems like in vitro cell lines, in vitro 3D organoid models and in vivo animal models. Apart from being used in establishing ASD models, CRISPR-Cas9 can also be used to treat the complexities of ASD. The aim of this review was to summarize and critically analyse the CRISPR-Cas9-mediated discoveries in the field of ASD.

Keywords: Autism spectrum disorder, CRISPR-Cas9, Cellular models, Organoids, Animal models, Therapeutic strategies

Core Tip: There are several reviews in the literature explaining the underlying mechanisms contributing to the pathophysiology of autism spectrum disorder by performing several preclinical experiments. Given the significant role of genetics (de novo or inheritable) in the development of autism spectrum disorder, disease specific models should be established for investigating the mechanism involved. Therefore, this review specifically focused on the use of an emerging genomic editing tool, clustered regularly inters-paced palindromic repeats/Cas9, for generating different types of preclinical models as well as new therapeutic options, providing a novel insight into the disease.