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Drp1 siRNA
- Development stage
- Preclinical
- Lead developer
- Janssen Research & Development
- 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
- Administration
- Subcutaneous
01
Overview
Drp1 siRNA is an experimental small interfering RNA (siRNA) therapeutic designed to silence the expression of Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission. In the context of liver disease research, specifically non-alcoholic steatohepatitis (NASH), the siRNA is conjugated to N-acetyl-galactosamine (GalNAc) to enable targeted delivery to hepatocytes via the asialoglycoprotein receptor (ASGPR). While initial hypotheses suggested that inhibiting mitochondrial fission might prevent steatosis, research conducted by Janssen Research & Development and academic partners indicates that hepatic Drp1 knockdown in adult mice may actually exacerbate NASH by activating the mitochondrial integrated stress response (ISR) through the Oma1-Atf4 pathway, leading to increased liver inflammation and fibrosis.
- Other names
- Dynamin-related protein 1 siRNAGalNAc-Drp1 siRNAGalNAc-Drp-1 siRNAGalNAc-Drp 1 siRNADNM1L siRNADNM-1L siRNADNM 1L siRNA
02
Targets
DNM1L (Dynamin-related protein 1)ASGPR (Asialoglycoprotein Receptor 1)
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