Targeting cancer epigenetics with CRISPR-dCAS9: Principles and prospects
- Methods. 2021 Mar:187:77-91. doi: 10.1016/j.ymeth.2020.04.006.
- 1. Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA. Electronic address: [email protected].
- 2. Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA; Comprehensive Center for Healthy Aging, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA; Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA; Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA; Comprehensive Diabetes Center, University of Alabama Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA. Electronic address: [email protected].
Cancer therapeutics is an ever-evolving field due to incessant demands for effective and precise treatment options. Over the last few decades, Cancer treatment strategies have shifted somewhat from surgery to targeted precision medicine. CRISPR-dCas9 is an emerging version of precision Cancer therapy that has been adapted from the prokaryotic CRISPR-Cas system. Once ligated to epigenetic effectors (EE), CRISPR-dCas9 can function as an epigenetic editing tool and CRISPR-dCas9-EE complexes could be exploited to alter cancerous epigenetic features associated with different Cancer hallmarks. In this article, we discuss the rationale of epigenetic editing as a therapeutic strategy against Cancer. We also outline how sgRNA-dCas9 was derived from the CRISPR-Cas system. In addition, the current status of sgRNA-dCas9 use (in vivo and in vitro) in Cancer is updated with a molecular illustration of CRISPR-dCas9-mediated epigenetic and transcriptional modulation. As sgRNA-dCas9 is still at the developmental phase, challenges are inherent to its use. We evaluate major challenges in targeting Cancer with sgRNA-dCas9 such as off-target effects, lack of sgRNA designing rubrics, target site selection dilemmas and deficient sgRNA-dCas9 delivery systems. Finally, we appraise the sgRNA-dCas9 as a prospective Cancer therapeutic by summarizing ongoing improvements of sgRNA-dCas9 methodology.