CRISPR-dCas9 epigenetic reprogramming in cancer: platforms, immuno-modulation and delivery challenges.
Level 5 - mechanism / opinion, no new human data
Narrative review of preclinical bench research and mechanisms without clinical human data.
PubMed 42229577 · doi:10.1016/j.gene.2026.150246
What was done
This narrative review synthesizes peer-reviewed preclinical literature from 2015 to 2025 on CRISPR-dCas9 (catalytically dead Cas9) epigenetic reprogramming in oncology. It evaluates emerging technological strategies, including multi-effector platforms (e.g., SunTag arrays, SSSavi modular docking, CRISPRoff), precision enhancer editing (enCRISPRa/enCRISPRi), immune-modulatory epigenetic targeting, and in vivo delivery platforms.
What was found
The abstract reports no numerical values or quantitative metrics. Qualitatively, it highlights that dCas9 systems achieve locus-specific gene activation or silencing without altering genomic DNA. Preclinical applications demonstrate targeted upregulation of anti-tumor immune markers, including NK/T-cell ligands (MICA/MICB) and antigen-presentation machinery (MHC I/II), while noting persistent translational challenges related to delivery efficiency, context-dependence, and off-target effects.
Why it matters
Epigenetic editing provides a reversible approach to modulating oncogenic expression and anti-tumor immunity without double-stranded DNA breaks. This synthesis outlines the multi-effector platforms and translational roadblocks that must be resolved before dCas9 therapies can advance to clinical trials.
Limits
The paper is a non-systematic narrative review with no human clinical data (all highlighted advances are preclinical). The abstract provides no quantitative comparisons, effect sizes, or study selection counts. Key translational hurdles—such as in vivo delivery efficiency, durability of epigenetic marks, and potential off-target binding—remain largely unresolved.
Cited by
- supports CRISPR-based epigenetic editing can turn genes on or off without cutting the underlying DNA sequence.