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MBO-asGCS
- Development stage
- Preclinical
- Lead developer
- University of Louisiana at Monroe
- Modality
- MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, 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, Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Intratumoral, Intravenous
01
Overview
MBO-asGCS is a second-generation mixed-backbone antisense oligonucleotide designed to target and silence the human glucosylceramide synthase (GCS) gene. Developed by researchers at the University of Louisiana at Monroe, MBO-asGCS consists of a 20-mer phosphorothioate DNA sequence with 2'-O-methyl RNA modifications at both the 5' and 3' ends to enhance nuclease resistance and stability. By downregulating GCS expression, MBO-asGCS inhibits the glycosylation of ceramide into glucosylceramide, leading to the accumulation of cellular ceramide and the restoration of wild-type p53-dependent apoptotic pathways. This mechanism effectively eliminates breast cancer stem cells (BCSCs), reduces tumor metastasis, and reverses multidrug resistance (MDR) to chemotherapeutic agents such as doxorubicin in drug-resistant cancer models.
- Other names
- mixed-backbone antisense glucosylceramide synthase oligonucleotidemixed-backbone oligonucleotide against glucosylceramide synthase
02
Targets
UGCG (UDP-glucose ceramide glucosyltransferase)
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