Eksi YE, Sanlioglu AD, Akkaya B, Ozturk BE, Sanlioglu S. Genome engineering and disease modeling via programmable nucleases for insulin gene therapy: Promises of CRISPR/Cas9 technology . World J Stem Cells 2021; 13(6): 485-502 [PMID: 34249224 DOI: 10.4252/wjsc.v13.i6.485]
Corresponding Author of This Article
Salih Sanlioglu, VMD, PhD, Chairman, Professor, Department of Gene and Cell Therapy, Akdeniz University Faculty of Medicine, Dumlupınar Boulevard, Campus, Antalya 07058, Turkey. ssanlioglu@icloud.com
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Jun 26, 2021; 13(6): 485-502 Published online Jun 26, 2021. doi: 10.4252/wjsc.v13.i6.485
Genome engineering and disease modeling via programmable nucleases for insulin gene therapy: Promises of CRISPR/Cas9 technology
Yunus E Eksi, Ahter D Sanlioglu, Bahar Akkaya, Bilge Esin Ozturk, Salih Sanlioglu
Yunus E Eksi, Ahter D Sanlioglu, Bahar Akkaya, Salih Sanlioglu, Department of Gene and Cell Therapy, Akdeniz University Faculty of Medicine, Antalya 07058, Turkey
Bilge Esin Ozturk, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213, United States
Author contributions: Eksi YE drafted the manuscript and prepared the figures; Sanlioglu AD prepared and revised the manuscript; Akkaya B and Ozturk BE revised the manuscript; Sanlioglu S designed both the study and the figures.
Supported bythe Akdeniz University Scientific Research Commission and the Scientific and Technological Research Council of Turkey, No. TUBITAK-215S820.
Conflict-of-interest statement: The authors declare no conflict 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Salih Sanlioglu, VMD, PhD, Chairman, Professor, Department of Gene and Cell Therapy, Akdeniz University Faculty of Medicine, Dumlupınar Boulevard, Campus, Antalya 07058, Turkey. ssanlioglu@icloud.com
Received: January 27, 2021 Peer-review started: January 27, 2021 First decision: February 28, 2021 Revised: April 2, 2021 Accepted: June 16, 2021 Article in press: June 16, 2021 Published online: June 26, 2021 Processing time: 149 Days and 22.8 Hours
Abstract
Targeted genome editing is a continually evolving technology employing programmable nucleases to specifically change, insert, or remove a genomic sequence of interest. These advanced molecular tools include meganucleases, zinc finger nucleases, transcription activator-like effector nucleases and RNA-guided engineered nucleases (RGENs), which create double-strand breaks at specific target sites in the genome, and repair DNA either by homologous recombination in the presence of donor DNA or via the error-prone non-homologous end-joining mechanism. A recently discovered group of RGENs known as CRISPR/Cas9 gene-editing systems allowed precise genome manipulation revealing a causal association between disease genotype and phenotype, without the need for the reengineering of the specific enzyme when targeting different sequences. CRISPR/Cas9 has been successfully employed as an ex vivo gene-editing tool in embryonic stem cells and patient-derived stem cells to understand pancreatic beta-cell development and function. RNA-guided nucleases also open the way for the generation of novel animal models for diabetes and allow testing the efficiency of various therapeutic approaches in diabetes, as summarized and exemplified in this manuscript.
Core Tip: In this review, CRISPR/Cas9 nuclease is deployed in the generation of cellular and animal models of diabetes, which are suitable for the testing of the treatment efficacy of novel insulin gene therapy approaches.
