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PMLA-LLL-AON
- Development stage
- Preclinical
- Lead developer
- Cedars-Sinai
- 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, Biodegradable Polymers → Polymer-based Nanoparticles → Nanoparticles → Drug Delivery Systems
- Administration
- Intravenous
01
Overview
PMLA-LLL-AON is a nanobioconjugate therapeutic candidate developed for the treatment of glioblastoma. It is built upon a biodegradable and non-immunogenic polymalic acid (PMLA) polymer backbone, which serves as a scaffold for the delivery of antisense oligonucleotides (AONs). These AONs are specifically designed to target and inhibit the synthesis of laminin-411, a vascular basement membrane protein that is highly overexpressed in approximately 75% of glioblastoma patients and plays a critical role in tumor angiogenesis. To ensure efficient intracellular delivery, the conjugate incorporates trileucine (LLL) as a pH-dependent endosomal escape unit, allowing the AONs to bypass endosomal degradation and reach the cytoplasm. Preclinical research conducted at Cedars-Sinai Medical Center has demonstrated that PMLA-LLL-AON significantly reduces tumor volume and inhibits laminin-411 expression in human glioma xenograft models, suggesting its potential as a targeted anti-angiogenic therapy for brain tumors.
- Other names
- PMLA-LLL-AON against laminin-411PMLA-LLL-AON(411)
02
Targets
TFRC (Transferrin Receptor)Laminin-411 messenger RNA
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