Beyond DNA—CRISPR technologies for epigenome editing and transcriptional regulation in disease: A scoping review

@article{oladipo2026beyond,
  title = {{Beyond DNA—CRISPR technologies for epigenome editing and transcriptional regulation in disease: A scoping review}},
  author = {Elijah Kolawole Oladipo and Victoria Oluwayemisi Adubiaran and Aanuoluwa Temitayo Iyiola and Biobele Winner Sokari and Ummulkhairi Tukur and Nimah Adejoke Adeoye and Augusta Edet Udo and Ifeoma Vivian Anyia and Juwaretu Ahuoiza Musa and Elibe Patricia and Edikan Umoh and Hezekiah Oluwajoba Awobiyi and Oluwanifemi Omodara Ogunleye and Gospel Ndunaka and Oluwaseyi Samuel Akinpelu and Helen Onyeaka},
  journal = {Clinical and Translational Discovery},
  year = {2026},
  month = oct,
  doi = {10.1002/ctd2.70226},
  url = {https://doi.org/10.1002/ctd2.70226},
  note = {CC BY},
}

TY  - JOUR
TI  - Beyond DNA—CRISPR technologies for epigenome editing and transcriptional regulation in disease: A scoping review
AU  - Elijah Kolawole Oladipo
AU  - Victoria Oluwayemisi Adubiaran
AU  - Aanuoluwa Temitayo Iyiola
AU  - Biobele Winner Sokari
AU  - Ummulkhairi Tukur
AU  - Nimah Adejoke Adeoye
AU  - Augusta Edet Udo
AU  - Ifeoma Vivian Anyia
AU  - Juwaretu Ahuoiza Musa
AU  - Elibe Patricia
AU  - Edikan Umoh
AU  - Hezekiah Oluwajoba Awobiyi
AU  - Oluwanifemi Omodara Ogunleye
AU  - Gospel Ndunaka
AU  - Oluwaseyi Samuel Akinpelu
AU  - Helen Onyeaka
PY  - 2026
DA  - 2026/10/26
JO  - Clinical and Translational Discovery
DO  - 10.1002/ctd2.70226
UR  - https://doi.org/10.1002/ctd2.70226
AB  - Background CRISPR‐derived epigenome editors enable locus‐specific control of gene expression without changing the underlying DNA sequence, creating therapeutic opportunities for dosage‐sensitive disorders, imprinting diseases, aberrant gene activation and reversible cell‐state engineering. Main body This scoping review maps mechanistic classes, target‐validation strategies, emerging platforms, translational evidence and unresolved risks of CRISPR‐based epigenome editing. A structured PubMed/MEDLINE search and citation‐chain review were updated in July 2026, with a targeted update of recent peer‐reviewed literature before revision. The field has progressed from CRISPR interference (CRISPRi) and activation to direct rewriting of DNA methylation and histone marks, programmable transcriptional memory, compact effectors, transient ribonucleoprotein or mRNA delivery, and externally controllable systems. Preclinical studies demonstrate correction of dosage‐sensitive and imprinting phenotypes, programmable regulation in human neurons and primary immune cells, and durable in vivo silencing after transient delivery. Target selection nevertheless requires orthogonal validation: nuclease knockout, conditional loss‐of‐function, CRISPRi, rescue, and reverse‐editing experiments answer different biological questions and should be interpreted together when establishing causality. The absence of DNA cleavage does not make epigenome editing intrinsically risk free. Development must address seed‐sequence‐mediated off‐target regulation, chromatin spreading, allele and cell‐type specificity, persistence, immune responses, delivery constraints and uncertainty regarding the relationship between a molecular epigenetic change and clinical phenotype. CONCLUSION CRISPR epigenome editing is approaching clinical translation, but adoption will depend on rigorous causal target validation, standardized reporting, multilayer specificity assays, controllable delivery and evidence that corrected expression remains within a safe physiological window.
SN  - 2768-0622
ER  -