Harnessing the potential of gene editing technology using CRISPR in inflammatory bowel disease

Abstract

The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease (IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease, human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm (Glycine amidinotransferase, mitochondrial), nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore, since Crohn’s disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity, protospacer adjacent motifs and crossfire between different target sites. However, these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.

Keywords: Clustered regularly interspersed short palindromic repeats; Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Gene excision; Gene editing; Gene therapy; Financial impact of inflammatory bowel disease on healthcare; Clustered regularly interspersed short palindromic repeats crossfire

Core tip: Using clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) to harness the potential of gene editing technology implicated in inflammatory bowel disease. This revolutionary way of editing genes and its application of gene manipulation is only gaining momentum. Genes such as Gatm (Glycine amidinotransferase, mitochondrial) and nucleotide-binding oligomerization domain-containing protein 2 have been utilized to show CRISPR is able to manipulate these genes precisely, and this is just the beginning.