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LNP-siTWEAK-R
- Development stage
- Preclinical
- Lead developer
- Brigham and Women's Hospital
- 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, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
LNP-siTWEAK-R is a preclinical lipid nanoparticle (LNP) formulation encapsulating small interfering RNA (siRNA) designed to target and silence the TWEAK receptor (TWEAK-R, also known as TNFRSF12A or Fn14) [0982]. Developed by researchers at Brigham and Women's Hospital, Harvard Medical School, and collaborating institutions, the therapeutic candidate is designed to target stromal cells, specifically pathogenic fibroblasts, to disrupt the autocrine TWEAK/TWEAK-R signaling circuit that drives persistent fibroblast activation, inflammation, and extracellular matrix production [0982]. In preclinical models of systemic sclerosis (SSc), intravenous administration of LNP-siTWEAK-R demonstrated therapeutic efficacy by reducing multi-organ fibrosis in the lungs, skin, and esophagus [0982].
- Other names
- LNP-siTWEAKRlipid nanoparticles encapsulating siRNA targeting TWEAK-R
02
Targets
AGO2/RISC (Protein Argonaute-2 (AGO2) and RNA-induced silencing complex (RISC))TNFRSF12A (Tumor necrosis factor-like weak inducer of apoptosis receptor)TNFSF12 (TWEAK)
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