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Dnv mRNA-LNP
- Development stage
- Preclinical
- Lead developer
- Stowers Institute for Medical Research
- Modality
- mRNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Peptides, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
Dnv mRNA-LNP is an experimental mRNA-based therapeutic consisting of a lipid nanoparticle (LNP) encapsulating mRNA that encodes a de novo designed peptide, "Dnv". Developed using AI-guided peptide design (RFdiffusion and AlphaFold), the Dnv peptide is engineered to bind with high affinity to hydrophobic hotspots within the AKT kinase pocket. This binding disrupts the interaction between AKT and β-catenin, specifically inhibiting AKT-mediated phosphorylation of β-catenin at Ser552. By targeting this signaling axis, the drug aims to eliminate leukemia stem cells (LSCs), which are responsible for chemoresistance and relapse in hematologic malignancies like acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). Preclinical studies indicate that Dnv mRNA-LNP reduces LSC populations and enhances anti-tumor immunity by reprogramming CD8+ T-cells, without the cardiotoxicity associated with conventional chemotherapies like doxorubicin.
- Other names
- Dnv mRNAARP-Dnv
02
Targets
AKT (RAC-alpha serine/threonine-protein kinase)CTNNB1 (Beta-catenin)
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