Enhancing KLF15 activity in cardiomyocytes: a novel approach to prevent pathological reprogramming and fibrosis via nuclease-deficient dCas9VPR - PubMed
4 hours ago
- #cardiomyopathy
- #KLF15
- #CRISPRa
- Enhancing KLF15 activity in cardiomyocytes using nuclease-deficient dCas9VPR prevents pathological reprogramming and fibrosis.
- Network-based analysis identified KLF15 as a key transcription factor with altered activity in pathological cardiomyocytes.
- CRISPRa (CRISPR/dCas9-based transcriptional enhancement) restored KLF15 activity, suppressing pathological gene expression and improving metabolic homeostasis.
- KLF15-dependent regulation of AZGP1 mediates a novel anti-fibrotic effect via cardiomyocyte-fibroblast crosstalk.
- KLF15 is a downstream target of the TGF-β canonical signaling pathway in human cardiomyocytes.
- An AAV vector with a small CRISPRa system was engineered for clinical applications in human cardiomyocytes.
- The study demonstrates CRISPRa as an effective epigenetic intervention for non-genetic heart failure.