Cardiology. 2026 Aug 19:1-25. doi: 10.1159/000553321. Online ahead of print.
ABSTRACT
BACKGROUND: Cell-specific epigenetic editing provides a new approach to the therapy of cardiovascular disease (CVD) by rewriting pathological chromatin and RNA marks in exactly those cell populations responsible for causing disease. CVD is caused by interactions of genetics and environment on cell-type-specific epigenomic programs. Interventions that alter DNA methylation, histone marks, or RNA modifications can therefore correct maladaptive gene expression without altering DNA sequence.
SUMMARY: Recently developed technologies such as dCas9 fused to writers/erasers allow programmable, locus-directed modulation of promoters, enhancers, and transcripts. Proof-of-principle in vivo work has shown durable target silencing, illustrating both the potency and persistence of epigenetic edits. To achieve therapeutic benefit, cell-targeting strategies and rigorous single-cell/multi-omic validation of on-target activity and off-target safety will be required. Major translational challenges include scalable, cardiac-selective delivery, immune responses to vectors/editors, long-term monitoring for unintended chromatin changes, and regulatory pathways for nongenotoxic but durable interventions.
KEY MESSAGES: Altogether, cell-specific epigenetic editing holds very high therapeutic value for atherosclerosis, cardiomyopathy, and fibrosis, provided that delivery, specificity, and safety challenges are also addressed.
PMID:42616698 | DOI:10.1159/000553321