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siGREM1-APE nanoparticle
- Development stage
- Preclinical
- Lead developer
- University College Cork
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Nanoparticles → Drug Delivery Systems
- Administration
- Topical
01
Overview
siGREM1-APE nanoparticle (also referred to as DOP128) is an experimental RNA-based therapeutic developed by researchers at University College Cork for the treatment of intestinal fibrosis in Crohn’s disease. The drug consists of a small interfering RNA (siRNA) targeting Gremlin-1 (GREM1), a bone morphogenetic protein (BMP) antagonist and master regulator of fibroblast activation, encapsulated within an APE-nanoparticle delivery system. In preclinical studies using primary human small-intestinal fibroblasts, the nanoparticle demonstrated high transfection efficiency and potent knockdown of GREM1, leading to the suppression of TGFβ-mediated SMAD2/3 signaling and a significant reduction in profibrotic markers like CTGF, COL1A1, and α-SMA. The platform is being optimized for mucosal delivery to provide a targeted antifibrotic strategy for fibrostenotic Crohn’s disease.
- Other names
- siRNA-APE nanoparticleNP-siGREM1NP-siGREM-1NP-siGREM 1
02
Targets
GREM1 (Gremlin-1)
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