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CpG-STAT3ASO
- Development stage
- Preclinical
- Lead developer
- City of Hope
- 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
- Administration
- Intravenous, Intratumoral, Intracranial, Subcutaneous
01
Overview
**CpG-STAT3ASO** is a bifunctional synthetic oligonucleotide conjugate linking a Toll-like receptor 9 (TLR9) agonist CpG oligodeoxynucleotide (ODN) to a chemically modified antisense oligonucleotide (ASO) targeting **STAT3** mRNA. The CpG moiety enables selective uptake and activation in antigen-presenting cells (APCs) such as dendritic cells, macrophages, B cells, and myeloid-derived suppressor cells (MDSCs), while the ASO induces RNase H1-dependent cleavage of STAT3 mRNA, leading to rapid STAT3 protein knockdown. This dual mechanism breaks tumor immunosuppression, reprograms tolerogenic myeloid cells, and elicits antitumor T-cell responses, showing potent activity against immunologically "cold" tumors including prostate cancer, head and neck squamous cell carcinoma (HNSCC), and glioma in preclinical models, with improved biodistribution and efficacy over STAT3ASO alone.
- Other names
- CpG-STAT3ASOCpG-STAT-3ASOCpG-STAT 3ASOCpG-STAT3 dsASOCpG-STAT-3 dsASOCpG-STAT 3 dsASO
02
Targets
TLR9 (Toll-like receptor 9)
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