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Z-GP-MEF2D ASO
- Development stage
- Preclinical
- Lead developer
- Nanfang Hospital, Southern Medical University
- Modality
- Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics
01
Overview
Z-GP-MEF2D ASO is a novel, pericyte-targeting prodrug consisting of a 5'-carboxylated antisense oligonucleotide (ASO) conjugated to a benzyloxy carbonyl-blocked GlyPro (Z-GP) dipeptide. It is designed to target and knock down myocyte-specific enhancer factor 2D (MEF2D) specifically in tumor pericytes (TPCs). The prodrug is site-specifically activated by fibroblast activation protein alpha (FAP alpha) endopeptidase, which is highly expressed in the tumor microenvironment. By depleting MEF2D in pericytes, Z-GP-MEF2D ASO realigns B-cell differentiation, promotes tertiary lymphoid structure (TLS) maturation, and enhances the infiltration of cytotoxic CD8+ T cells and NK cells. This remodeling of the immunosuppressive tumor immune microenvironment (TIME) significantly improves the efficacy of lung cancer immunotherapy.
- Other names
- Z-GP-MEF2D antisense oligonucleotideZ-GP-MEF-2D antisense oligonucleotideZ-GP-MEF 2D antisense oligonucleotidebenzyloxy carbonyl-blocked GlyPro-MEF2D antisense oligonucleotide
02
Targets
MEF2D
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