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anti-miRNA inhibitor miR-125b + anti-miRNA inhibitor miR-148b
- Development stage
- Preclinical
- Lead developer
- University of Pittsburgh
- 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
01
Overview
anti-miRNA inhibitor miR-125b + anti-miRNA inhibitor miR-148b is a combination therapeutic consisting of two synthetic Locked Nucleic Acid (LNA) antisense oligonucleotides. These inhibitors are designed to target and neutralize microRNA-125b and microRNA-148b, which are overexpressed in activated B-cell type-diffuse large B-cell lymphoma (ABC-DLBCL) and MALT lymphoma. These specific miRNAs act as oncomiRs by directly targeting and downregulating the tumor suppressor G-protein-coupled receptor kinase 2 (GRK2). By inhibiting these miRNAs, the combination therapy restores GRK2 protein levels, which then binds to and inhibits the scaffolding and proteolytic activities of the MALT1 oncoprotein. This intervention disrupts the CARMA1-BCL10-MALT1 (CBM) signalosome, leading to reduced NF-κB activation and the suppression of tumor cell proliferation. Preclinical studies have demonstrated that this combination can abrogate the growth of ABC-DLBCL xenograft tumors in vivo.
- Other names
- anti-miR-125b + anti-miR-148bmiR-125b inhibitor + miR-148b inhibitoranti-miRNA Locked Nucleic Acids miR-125b and miR-148b
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