Comparative performance of CRISPR epigenome gene activation: a systematic review on potency and temporal dynamics in mammalian models
Epigenome editing refers to the targeted alteration of gene regulatory states without altering the underlying DNA sequence in a heritable or not manner, directly or indirectly. Specifically, CRISPR activation (CRISPRa) is a epigenome editing system based on the activity of a Cas9 that lacks endonuclease activity (dCas9) associated with transcriptional or epigenetic effector domains to promote gene overexpression, without permanent DNA modifications. A single-guide RNA directs the CRISPRa complex to a specific genomic region to enhance transcription of a target gene. Despite the rapid development of diverse CRISPRa effector systems, no systematic review has comprehensively compared their activation efficiency and kinetic profiles. This gap limits evidence-based selection of effector domains for experimental or therapeutic applications. Therefore, this systematic review aims to compare the performance of CRISPR-dCas9-based effector domains for gene upregulation across eukaryotic and mammalian experimental models, focusing on activation magnitude and stability over time. By doing so, this review is expected to provide a framework to guide experimental design and translational applications.