mRNA-engineered CRISPR-Cas epigenetic editors enable durable and efficient gene silencing in vivo - PubMed
5 days ago
- #mRNA delivery
- #CRISPR
- #epigenetic editing
- mRNA-engineered CRISPR-Cas epigenetic editors enable durable and efficient gene silencing in vivo.
- Compact EEs (CRISPR OFF-EE) designed using SpCas9, intein-split-SpCas9, or Cas-SF01 (Cas12i3 variant).
- Optimized mRNA architecture and LNP delivery used for efficient in vivo delivery.
- Single LNP administration in mice reduced PCSK9 by 83.2% and LDL-C by 51.4%, lasting 180 days.
- SF01-based EEs showed higher specificity with fewer off-target methylation events than SpCas9-based ones.
- LNP formulation demonstrated a favorable safety profile with liver-tropic activity.
- Platform enables precise and durable epigenetic silencing using transiently delivered mRNA editors.