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Dnv mRNA-LNP

Development stage
Preclinical
Lead developer
Stowers Institute for Medical Research
Modality
Peptides, mRNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, 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

CTNNB1 (Beta-catenin)AKT (RAC-alpha serine/threonine-protein kinase)

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