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CRISPR-dCas9 Tools for Precision DNA Methylation Editing in Regenerative Therapies | ||
| Regenerative Biomedicine | ||
| Volume 1, Issue 3, July 2025, Pages 148-154 PDF (816.64 K) | ||
| Document Type: Mini-Review | ||
| DOI: 10.22034/jrb.2025.539.1025 | ||
| Authors | ||
| Mohammad Hossein Darvishali; Ehsan Farashahi Yazd* | ||
| Genetic Engineering and Genome Editing Laboratory, Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| Abstract | ||
| DNA methylation serves as a crucial epigenetic modification, influencing gene expression and determining stem cell fate along with its differentiation capabilities. Through the precise modulation of methylation patterns, it is possible to regulate cellular identity and differentiation potential, leading to notable advancements in cancer management, regenerative therapies, and personalized medicine. To this end, the emergence of the CRISPR-dCas9 system has facilitated accurate modifications of the epigenome. These tools signify notable progress in the precise and focused modification of the methylome, all the while preserving the integrity of the original genetic sequence. By leveraging this technology, the combination of nuclease-deactivated Cas9 (dCas9) with methylation-modifying enzymes like DNMT3A or TET1 enables targeted hypermethylation or demethylation at specific genomic loci. This specific epigenetic manipulation offers new avenues for disease modeling, cellular reprogramming, and the development of cutting-edge regenerative therapies. Notable applications include the activation of lineage-specific genes to guide stem cell differentiation and the correction of epigenetic abnormalities in disease models, including Rett syndrome and hematological malignancies. While the potential is significant, obstacles persist, especially concerning unintended effects, the efficiency of editing, and the in vivo delivery of these large complexes. Continuous improvements in sgRNA design, delivery mechanisms, and effector engineering are tackling these challenges. Ultimately, with the ongoing advancements in technology, CRISPR-dCas9-based DNA methylation editing presents significant possibilities for the fields of personalized and regenerative medicine. | ||
| Keywords | ||
| CRISPR-dCas9; DNA methylation; Epigenetic memory; Epigenome editing; Regenerative medicine | ||
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