CRISPRoff mRNA

**CRISPRoff mRNA** is an investigational messenger-RNA epigenetic-editing therapy that transiently expresses the CRISPRoff programmable transcriptional-memory editor. The encoded editor is a catalytically inactive Cas9 fusion incorporating ZNF10 KRAB, DNMT3A, and DNMT3L effector domains; when supplied with target-specific single-guide RNAs, it deposits repressive epigenetic marks at selected regulatory DNA regions and can produce durable gene silencing without introducing DNA double-strand breaks. In glioblastoma models, CRISPRoff mRNA delivered by electroporation or lipid nanoparticles has been used to silence the MGMT promoter and sensitize tumors to temozolomide, while related experiments targeted the TERT promoter to suppress telomerase expression and induce replicative senescence. This remains a preclinical, guide-dependent platform rather than a standardized clinical drug product. ([pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/39998382/))

Other names

mRNA-based CRISPRoff