Abstract: SA-PO0251
Kidney-Specific Delivery of siRNAs Opens Options for Targeted Oligotherapeutic Treatment of CKD
Session Information
- Pharmacology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Granqvist, Anna L., Ribocure Pharmaceuticals AB, Mölndal, Västra Götaland County, Sweden
- Li, Shaohua, Suzhuo Ribo Life Science Co Ltd, Kunshan, Jiangsu, China
- Liu, Yanan, Suzhuo Ribo Life Science Co Ltd, Kunshan, Jiangsu, China
- Wallentin, Hanna Ilse, Ribocure Pharmaceuticals AB, Mölndal, Västra Götaland County, Sweden
- Gan, Li Ming, Ribocure Pharmaceuticals AB, Mölndal, Västra Götaland County, Sweden
- Gao, Shan, Suzhuo Ribo Life Science Co Ltd, Kunshan, Jiangsu, China
Background
There is still an unmet medical need for patients suffering from renal disorders. The use of siRNA as a therapeutic modality beyond hepatic targets is limited due to lack of efficient delivery systems. Here we describe a promising approach to specifically and efficiently deliver siRNA to the kidney, suggesting a new therapeutic approach for patients with kidney disease.
Methods
The team has discovered and developed peptide-siRNA conjugates that specifically deliver siRNA to the proximal tubular cells. The distribution profile and exposure of the optimized conjugates were evaluated using IVIS (Cy5 labelled siRNA), microscopic imaging and mass spectrometry. The potency, knock down level and duration, as well as regulation of relevant efficacy biomarkers were measured in both healthy and renally impaired in vivo models.
Results
The optimized peptide-siRNA conjugates are specifically taken up by the proximal tubular cells cross-species (mouse, rat and monkeys), with limited signal in liver. We saw a robust 60-80% knockdown in the kidney depending on the target of choice and siRNA sequence explored. In addition, we could detect physiological effects in both diabetic and fibrotic mice models, clearly indicating that we are hitting the target gene in a relevant and efficient way. Both the peptide + linker and the full conjugate demonstrated a good safety profile.
Conclusion
By using a peptide conjuagtion approach we were able to specifically and efficiently silencing gene and protein expression in the proximal tubuli and thereby demonstrate a relevant physiological effect. Our data opens for siRNA therapeutics beyond liver targets and hold promises for patients with kidney disease.