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Updated: May 9, 2026

CRISPR Epigenome Editing in Human Cells using Plasmid DNA Transfection and mRNA Nucleofection Delivery
Published on: May 30, 2025
CRISPR RNA-guided activation of endogenous human genes
Morgan L Maeder1, Samantha J Linder, Vincent M Cascio
11] Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA. [2] Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA. [3] Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts, USA. [4] Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
Short guide RNAs (gRNAs) can direct catalytically inactive CRISPR-associated 9 nuclease (dCas9) to repress endogenous genes in bacteria and human cells. Here we show that single or multiple gRNAs can direct dCas9 fused to a VP64 transcriptional activation domain to increase expression of endogenous human genes. This proof-of-principle work shows that clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems can target heterologous effector domains to endogenous sites in human cells.
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