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GRAD1405
- Development stage
- Preclinical
- Lead developer
- Gradalis
- Modality
- Viral-delivered RNAi → In Vivo RNAi → Gene Silencing → Gene Therapies, RNA Therapeutics → Nucleic Acid Therapeutics, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
GRAD1405 is a bi-functional short hairpin RNA interference (bi-shRNAi) therapeutic candidate developed by Gradalis Inc. for the treatment of KRAS-mutated solid tumors. Utilizing a proprietary DNA vector-based platform, GRAD1405 produces both siRNA-like and miRNA-like molecules designed to silence mutated KRAS genes, specifically targeting the G12C, G12D, and G12V variants. This dual mechanism involves both mRNA cleavage-dependent and cleavage-independent (translational repression) pathways, potentially offering enhanced efficacy over traditional siRNA approaches. The drug is encapsulated in a proprietary DOTAP-cholesterol liposomal delivery vehicle and has demonstrated robust, dose-related tumor growth control in preclinical models of non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic cancer.
02
Targets
Kirsten rat sarcoma viral oncogene homolog G12C messenger RNA (KRAS G12C mRNA)KRASG12V (KRAS G12V)
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