Therapeutic applications of CRISPR-Cas9 in diabetes mellitus: a perspective review

• Published in: Minerva Biotechnology and Biomolecular Research Vol. 35; no. 4; p. 238
• Main Authors: BORA, Jutishna, MALIK, Sumira, KISHORE, Shristi, RUSTAGI, Sarvesh, AHMAD, Faraz, FAGOONEE, Sharmila, PELLICANO, Rinaldo, HAQUE, Shafiul
• Format: Journal Article
• Language: English
• Published: Torino Edizioni Minerva Medica 01.12.2023
• Subjects: Animal models; Beta cells; Blood levels; Cell differentiation; CRISPR; Diabetes; Diabetes mellitus; Genomes; Homeobox; Hyperglycemia; Insulin; Nuclease; Pancreas; Pluripotency; Reviews; Therapeutic applications
• ISSN: 2724-542X; 1120-4826; 2724-5934; 1827-160X
• DOI: 10.23736/S2724-542X.23.02996-6

Diabetes mellitus (DM) is an excessively widespread condition resulting as a consequence of either autoimmune-mediated dysfunction of the pancreatic β-cells and abolishment of insulin production (Type I DM; T1DM), or deficient insulin production and irresponsiveness of cells to it (type II DM; T2DM). Either ways, the result is elevated blood glucose levels or hyperglycemia, the characteristic feature of DM. Tremendous efforts and resources have been spent in deciphering effective therapies/treatments against DM. In spite of hard-earned successes, the problems associated with DM still persist, warranting the need for exploration, development and application of novel dimensions in our quest for controlling this serious problem. Recent years have seen the emergence of promising genetic manipulation technologies, the clustered regularly interspaced short palindromic repeat (CRISPR) associated nucleases Cas being one of them. CRISPR-Cas9 technology has the potential to revolutionize and accelerate the gene editing-based therapies in the clinical practice. It can be fine-tuned for direct modification of specific genome sites in target cells, opening up the possibility for rectifying cellular and metabolic defects associated with diseases such as DM. For instance, genes (e.g., octamer-binding transcription factor 4; OCT 4 and pancreatic duodenal homeobox 1; PDX 1) involved in the differentiation pathway of human β-cells can be identified and amended in transplantable pluripotent stem cells. The present perspective review summarizes the recent experimental successes in cellular and animal models for the utilization of the CRISPR-Cas9 technology in DM research. Further, we conclude with a discussion regarding the critical shortcomings of this technology and suggest means to circumvent these, with the expectation that this review will serve as a relevant and timely research platform aiding global research for further identification of novel and efficient CRISPR-Cas9-based anti-DM treatment strategies.