CRISPR activation of endogenous PKD1 increases polycystin-1 levels and suppresses cellular features of ADPKD
Year: 2026
Type: article
Abstract: This study provides proof-of-concept for a CRISPR activation (CRISPRa)-based approach to ADPKD. CRISPRa targeting the PKD1 promoter increased polycystin-1 levels in mouse and human cells. Upregulation of a hypomorphic Pkd1 allele increased functional polycystin-1, corrected dysregulated signaling pathways, and suppressed cell proliferation and in vitro cyst formation. These results establish CRISPRa as a promising therapeutic approach to restore polycystin levels above a critical threshold and suppress cystogenesis in ADPKD.
Authors: Anubhav Chakraborty, Meekha M. Varghese, Darren P. Wallace, Christopher J. Ward, Alan S. L. Yu
Institution: University of Kansas Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Awards: Novel Approaches for the Control of Microbial Pathogens, CRISPR based gene therapy for Autosomal Dominant Polycystic Kidney Disease by reprogramming PKD1 transcription, University of Kansas Alzheimer's Disease Research Center (KU ADRC), Kansas PKD Research and Translation Core Center, The University of Kansas Cancer Center
OpenAlex ID: W7213903822