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.

中文翻译：

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利用 CRISPR-dCAS9 靶向癌症表观遗传学：原理和前景


由于对有效和精确的治疗方案的不断需求，癌症治疗是一个不断发展的领域。在过去的几十年里，癌症治疗策略已经从手术转向有针对性的精准医疗。 CRISPR-dCas9是一种新兴的精准癌症疗法，改编自原核CRISPR-Cas系统。一旦与表观遗传效应器 (EE) 连接，CRISPR-dCas9 就可以作为表观遗传编辑工具，并且 CRISPR-dCas9-EE 复合物可用于改变与不同癌症标志相关的癌症表观遗传特征。在本文中，我们讨论了表观遗传编辑作为癌症治疗策略的基本原理。我们还概述了 sgRNA-dCas9 是如何从 CRISPR-Cas 系统衍生而来的。此外，通过 CRISPR-dCas9 介导的表观遗传和转录调节的分子说明，更新了 sgRNA-dCas9 在癌症中的使用（体内和体外）的现状。由于 sgRNA-dCas9 仍处于开发阶段，其使用面临着固有的挑战。我们评估了使用 sgRNA-dCas9 靶向癌症的主要挑战，例如脱靶效应、缺乏 sgRNA 设计标准、靶位点选择困境以及 sgRNA-dCas9 递送系统缺陷。最后，我们通过总结 sgRNA-dCas9 方法的持续改进，将 sgRNA-dCas9 评估为一种前瞻性的癌症治疗方法。