Abstract: FR-PO0666
Potential One-Time Lipid Nanoparticle-Driven Gene Editing Therapy to Address ADPKD Caused by PKD1 Mutations
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Chaudhuri, Poulami, Helex, Cambridge, Massachusetts, United States
- Gaur, Neha, Helex, Cambridge, Massachusetts, United States
- Rohira, Harsha, Helex, Cambridge, Massachusetts, United States
- Kappagantu, Rakesh, Helex, Cambridge, Massachusetts, United States
- Gupta, Yugantak Raj, Helex, Cambridge, Massachusetts, United States
- Sembara, Gayathri, Unicas Biotech, Hyderabad, India
- Parate, Kanchan, Unicas Biotech, Hyderabad, India
- Dhondi, Naveen Kumar, Unicas Biotech, Hyderabad, India
- Kalvakuntla, Rohini, Helex, Cambridge, Massachusetts, United States
- Nishtala, Anirudh, Helex, Cambridge, Massachusetts, United States
Background
Autosomal Dominant Polycystic Kidney Disease (ADPKD), primarily caused by mutations in PKD1, is the most common rare genetic kidney disease and represents a significant unmet need. The development of advanced therapeutics for ADPKD and other genetic kidney disorders has been limited, largely due to challenges in achieving targeted delivery to the kidney.
Methods
Helex’s proprietary lipid nanoparticle (LNP) platform was used to deliver gene editing cargo to the kidney. Biodistribution was assessed using IVIS imaging in a moderate-to-severe Pkd1:fl/fl;Cdh16-CreERT2:ki/wt knockout mouse model following retrograde ureteral administration. In vitro studies were conducted in patient-derived ADPKD renal epithelial cells. Additional studies evaluated off-target effects, stability, and manufacturability of the LNP formulation.
Results
Significant LNP accumulation was observed in cystic kidneys of the ADPKD mouse model. In vitro, CRISPR-based genome editing targeting a regulatory region led to over two-fold upregulation of PKD1 expression and correction of multiple downstream cystogenic pathways, including reductions in pCREB, PKA-C, and mTOR. Off-target assessments showed a favourable safety profile. The formulation demonstrated reproducible scale-up and remained stable for over 60 days.
Conclusion
This proof of concept supports the disease-modifying potential of a mutation-agnostic, LNP-delivered gene editing therapeutic for ADPKD. It offers a promising new care paradigm for patients with PKD1-associated disease.