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LNP-ASO-LINCMD1

Development stage: Preclinical
Modality: Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration: Intravenous

Overview

LNP-ASO-LINCMD1 is an experimental liver-targeted therapeutic consisting of an antisense oligonucleotide (ASO) encapsulated in a lipid nanoparticle (LNP). It is designed to target the long non-coding RNA (lncRNA) LINCMD1, specifically the region that binds to the E3 ligase DZIP3. In metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma (MASH-HCC), LINCMD1 sequesters DZIP3, preventing the ubiquitination and degradation of the carnitine transporter OCTN2. By silencing LINCMD1, the drug restores DZIP3-mediated degradation of OCTN2, thereby reducing L-carnitine accumulation and preventing the depletion of intracellular acetyl groups. This restoration leads to increased acetylation of p53 (enhancing tumor suppression) and histone H3 (improving MHC-I antigen presentation), ultimately sensitizing tumors to immunotherapy such as anti-PD-1 agents.

Other names: LNP-delivered antisense oligonucleotide against LINCMD1

Targets

LINCMD1 (Long intergenic non-protein coding RNA, muscle differentiation 1)

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