Çağatay Özulu1, Oytun Erbaş1,2

1Institute of Experimental Medicine, Gebze-Kocaeli, Turkey
2Department of Physiology, Medical Faculty of Demiroğlu Bilim University, Istanbul, Turkey

Keywords: CRISPR/Cas9, gene editing, lncRNA, miRNA, Non-coding RNA, schizophrenia

Abstract

Schizophrenia is a genetically related mental disorder in which most genetic changes occur in non-coding regions of the human genome. In the past decade, an increasing number of non-coding regulatory RNAs (ncRNAs), including microRNA (miRNA) and long non-coding RNAs (lncRNAs), have been strongly associated with schizophrenia. However, understanding the workings of ncRNA and genetic mutations in the pathophysiology of schizophrenia has failed due to insufficient technology and lack of appropriate animal models to effectively manipulate ncRNA genes. Recently, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9; CRISPR/Cas9) has been developed to enable researchers to overcome these challenges. This review article mainly focuses on the use of CRISPR/Cas9 editing of these regions to demonstrate the causal relationship between mutations in non-coding regions of genomic DNA that express schizophrenia-related ncRNAs and the pathophysiology of schizophrenia. Furthermore, although CRISPR/Cas9 technology is still in its infancy and immature for use in the treatment of diseases, its potential to transform this advanced technology into a clinical treatment for schizophrenia will be discussed. This review describes the application of powerful and viable CRISPR/Cas9 technology to manipulate ncRNA genes associated with schizophrenia.