AUMantagomir™
Self-Delivering ASOs for miRNA Inhibition
AUMantagomir™
Self-Delivering ASOs for miRNA Inhibition
AUMantagomir™ oligos are specialized antisense oligonucleotides for microRNA (miRNA) inhibition. MicroRNAs are small regulatory RNAs that typically bind to mRNAs and repress their translation or cause degradation. AUMantagomir ASOs act as "antagomirs" – they bind to a specific miRNA of interest and prevent it from interacting with its natural mRNA targets.
Built on the same AUMsilence platform as our other products, AUMantagomir molecules are also self-delivering. They are designed to enter cells readily without transfection reagents and localize to both cytoplasm and nucleus. Once inside the cell, an AUMantagomir oligo will bind its complementary miRNA, blocking its function and often leading to its degradation.
Potent miRNA Silencing
AUMantagomir is highly effective at knocking down miRNA activity. Researchers have seen strong inhibition of miRNA function, with significant upregulation of miRNA target genes as a result of treatment. For instance, in rat hippocampal slices, treatment with an AUMantagomir against miR-134 led to a clear decrease in miR-134 levels and de-repression of its target genes.
No Transfection Required
Easy self-delivery is a hallmark advantage. You can add AUMantagomir directly to cell culture (including primary neurons or cardiomyocytes, which are often the subject of miRNA studies) and see uptake and activity. Primary tissue explants or organotypic slices can also be treated by simple incubation with AUMantagomir.
Minimal Toxicity
AUMantagomir shares the low toxicity profile of our other ASOs. Traditional miRNA inhibitors often require high concentrations or complex formulations that can cause cell stress. By avoiding transfection reagents and using a chemistry optimized for biocompatibility, AUMantagomir ensures that any observed effects are due to miRNA inhibition, not off-target toxicity.
High Binding Affinity to miRNA
The chemical modifications in AUMantagomir confer very high binding affinity to RNA targets. This means even low-abundance miRNAs can be effectively captured by the ASO. The high affinity also means that competitive binding against the miRNA's natural targets is won by the ASO – ensuring the miRNA is tied up by the inhibitor.
Mechanism of Action
MiRNA Binding: AUMantagomir ASOs are typically fully complementary (or heavily complementary) to the miRNA sequence of interest. A single miRNA (~22 nucleotides) can be entirely bound by the AUMantagomir. Upon binding, the ASO-miRNA duplex can prevent the miRNA from assembling with the RISC complex or from attaching to its target mRNAs. This neutralizes the miRNA's regulatory effect.
miRNA Inhibition vs. Degradation: Depending on the design, an AUMantagomir can work by steric blocking (simply binding the miRNA and preventing it from function) and/or by recruiting RNase H to degrade the miRNA. In many cases, the PS-modified ASO will result in the miRNA being degraded as part of an RNA:DNA hybrid, thereby reducing the miRNA's abundance.
Self-Delivery: Just like our other products, AUMantagomir oligos enter cells without needing a transfection agent. This is crucial for miRNA studies because many cell types of interest (neurons, primary tissue cells, etc.) are difficult to transfect.
Applications and Use Cases
Functional Studies of miRNAs
If you hypothesize a certain miRNA regulates a pathway (for example, miR-21 in cancer or miR-122 in liver metabolism), you can test this by inhibiting the miRNA with AUMantagomir and observing the outcome.
Target Discovery
Use AUMantagomir to help identify what genes a miRNA controls. By treating cells with an AUMantagomir, then performing transcriptomic analysis, you can see which transcripts go up – those are likely direct or indirect targets of the miRNA.
Disease Models
Many diseases involve dysregulated miRNAs (fibrosis, cancer, neurodegeneration). AUMantagomir can be used in cellular or animal models of disease to mimic therapeutic miRNA inhibition.
Hard-to-Deliver Systems
Want to inhibit a miRNA in primary macrophages, or in a neuron culture, or a plant protoplast? AUMantagomir is likely one of the few tools that can get into such cells without special methods.
AUMantagomir in Action - Select Published Studies
In a groundbreaking study on Alzheimer's disease (AD), researchers used AUMantagomir™ sdASO™ to inhibit microRNA-134-5p, which was found to be upregulated in Aβ(1-42)-induced AD conditions. Using AUMantagomir™, scientists achieved approximately 80% knockdown efficiency at a concentration of just 1 µM. In rat hippocampal slices, the AUMantagomir™ sdASO™ restored late long-term potentiation (LTP) and synaptic tagging and capture (STC), which are crucial for memory formation and normally impaired in AD. The study demonstrated that AUMantagomir™ elevated the expression of plasticity-related proteins, including CREB-1 and BDNF, which are typically downregulated in AD conditions. The self-delivering nature of AUMantagomir™ sdASO™ allowed direct application to hippocampal tissue slices without transfection reagents, highlighting its efficiency in targeting neuronal cells in complex tissues.
Reference: Baby et al., Aging Cell, 2020. "MicroRNA-134-5p inhibition rescues long-term plasticity and synaptic tagging/capture in an Aβ(1–42)-induced model of Alzheimer's disease."
In another pioneering study on space radiation damage, researchers used AUMantagomir™ sdASO™ to inhibit three key microRNAs (miR-16-5p, miR-125b-5p, and let-7a-5p) that were found to be dysregulated during space flight. Using a 3D human microvessel model exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation), scientists demonstrated that AUMantagomir™ treatment resulted in significant protection of vascular structures. The study showed that AUMantagomir™ sdASO™ targeting these three miRNAs preserved microvessel morphology and rescued angiogenesis. Additionally, the treatment significantly reduced DNA double-strand breaks and inflammation while restoring mitochondrial functions. The research revealed that AUMantagomir™ treatment rescued the expression of 21 key genes that are downregulated by space radiation exposure. This groundbreaking work has important implications for developing countermeasures to protect astronauts during long-duration space missions, such as future Mars expeditions.
Reference: McDonald et al., Nature Communications, 2024. "Space radiation damage rescued by inhibition of key spaceflight associated miRNAs."
Ready to Inhibit Your miRNA of Interest?
Order your custom AUMantagomir today. Our AI-driven design platform will create the optimal oligo sequence for your specific miRNA target. We offer personalized consultation to ensure you get the best results for your unique research needs.
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