AUMblock™
Self-Delivering ASOs for Steric Blocking of RNA Function
AUMblock™
Self-Delivering ASOs for Steric Blocking of RNA Function
AUMblock™ oligonucleotides are steric-blocking antisense oligonucleotides designed to bind target RNAs and modulate their function without inducing RNA cleavage. Unlike traditional knockdown antisense molecules, AUMblock ASOs act as physical blockers on the RNA – they interfere with processes like translation or splicing through steric hindrance, but do not trigger RNase H degradation of the target mRNA.
Built on AUM Biotech's advanced AUMsilence platform, these blocker oligos achieve high affinity binding to RNA while avoiding the RNAi pathway and any RISC or nuclease-mediated target slicing. As a result, the target RNA remains intact (no mRNA cleavage), allowing reversible regulation of its function. Like other AUM products, AUMblock oligos are engineered for self-delivery into cells without transfection reagents – no special conjugates or delivery vehicles are needed.
Steric Blocking Mechanism
AUMblock oligos bind to their target RNA sequence and physically obstruct the normal binding of cellular machinery, thereby altering RNA function. By design, they do not cleave or degrade the RNA target – instead, they exert their effects by getting in the way (steric hindrance). This allows for modulation of RNA function while keeping the RNA molecule intact.
Reversible RNA Modulation
Because AUMblock doesn't destroy the RNA, the effect is typically reversible – if the ASO dissociates or is metabolized, the RNA can resume normal function. This mechanism provides a tunable way to turn down or redirect gene expression at the RNA level without altering the RNA's overall abundance.
Self-Delivery Capability
AUMblock oligos possess the same self-delivering properties as our other sdASO™ products. They can enter cells without transfection reagents due to their advanced chemical modifications. This greatly simplifies experiments and minimizes toxicity, especially in hard-to-transfect cell types.
AI-Optimized Design
Our AUMblock oligos benefit from AUM's AI-powered design pipeline that analyzes target RNA structure and accessibility to select optimal binding sites. The sequences are designed for maximum specificity and efficacy, taking into account RNA secondary structure and minimizing off-target effects.
Mechanism of Action
Translation Blocking: If an AUMblock oligo binds in the 5′ untranslated region or across the start codon of an mRNA, it can prevent the ribosome or initiation factors from assembling on the transcript. This steric blockade of the translation machinery effectively stalls or prevents protein translation from that mRNA while leaving the mRNA itself intact.
Splice Modulation: If the oligo targets a pre-mRNA at a splice junction, intronic splicing enhancer, or other splicing factor binding site, it can block the recognition of that site by the splicing machinery. This steric hindrance can alter splicing outcomes – for example, causing skipping of an exon or inclusion of an alternative exon – thereby changing the mRNA isoform produced.
miRNA and lncRNA Interference: AUMblock oligos can also bind to regulatory RNA binding sites. For instance, an oligo complementary to a microRNA's seed-binding site on an mRNA will act as a target protector, preventing that microRNA from binding and repressing the mRNA. Similarly, binding to functional motifs on a long non-coding RNA could block an RNA-binding protein from interacting, thereby modulating the lncRNA's activity.
Applications and Use Cases
mRNA Translation Inhibition
By blocking ribosome access, AUMblock can suppress the production of a specific protein. This is useful for studying protein function (temporary loss-of-function experiments) or therapeutic knockdown of a protein without inducing RNA decay.
Splicing Modulation
AUMblock oligos can be directed to alter pre-mRNA splicing patterns. This has applications in correcting aberrant splicing or intentionally skipping an exon. For more targeted splicing applications, consider our specialized AUMskip product.
miRNA Blocking
AUMblock can function as a miRNA target protector. By binding to the miRNA's target sequence on a given mRNA, it protects that mRNA from miRNA-mediated repression. This approach is useful to validate miRNA–target interactions and to modulate gene expression post-transcriptionally.
RNA-Protein Interaction Blocking
Many RNAs have binding sites for proteins. A blocker oligo can occupy such a motif and act as a decoy, preventing the protein from binding. This allows you to study the functional importance of specific RNA-protein interactions in cellular pathways.
AUMblock in Action - Select Published Studies
In a groundbreaking melanoma study, researchers used AUMblock™ sdASO™ to investigate the function of the lncRNA SLNCR, which plays a critical role in melanoma progression and may help explain the observed sex bias in melanoma incidence and severity. Using AUMblock™ to sterically block specific protein-binding regions, scientists determined that SLNCR forms a complex with Androgen Receptor (AR) and the transcription factor EGR1, which normally activates the tumor suppressor p21. When AUMblock™ sdASO™ targeted the AR-binding region of SLNCR, researchers observed approximately 70% reduction in melanoma cell proliferation. The study revealed that SLNCR specifically recruits AR to EGR1-bound genomic loci, converting EGR1 from a transcriptional activator to a repressor at these sites. This regulatory triad of SLNCR-AR-EGR1 suppresses p21 expression, promoting melanoma progression. The self-delivering capability of AUMblock™ was crucial for effectively targeting nuclear lncRNAs in melanoma cells without transfection reagents, allowing precise dissection of complex lncRNA-protein interactions that drive oncogenesis. Reference: Schmidt et al., Cell Reports, 2019. "The lncRNA SLNCR Recruits the Androgen Receptor to EGR1-Bound Genes in Melanoma and Inhibits Expression of Tumor Suppressor p21."
In a follow-up study focused on therapeutic applications, investigators employed AUMblock™ sdASO™ to target the oncogenic lncRNA SLNCR1 by specifically blocking its interaction with the androgen receptor (AR). Using a combination of biochemical analyses and selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing, researchers identified that the N-terminal domain of AR binds a pyrimidine-rich motif in an unstructured region of SLNCR1. AUMblock™ sdASO™ was designed to sterically block this sequence-specific binding interaction. When applied to melanoma cells, the AUMblock™ treatment significantly reduced SLNCR1-mediated melanoma invasion by approximately 65% without affecting SLNCR1 expression levels. The study demonstrated that AUMblock™ oligonucleotides can effectively disrupt specific lncRNA-protein interactions without degrading the target RNA, providing a novel approach to target "undruggable" cancer pathways. This work highlights how AUMblock™ sdASO™ technology enables precise modulation of RNA function by disrupting specific protein binding sites while maintaining RNA integrity, opening new therapeutic avenues for cancers driven by lncRNA-protein complexes. Reference: Schmidt et al., Cell Reports, 2020. "Targeting the Oncogenic Long Non-coding RNA SLNCR1 by Blocking Its Sequence-Specific Binding to the Androgen Receptor."
Ready to Modulate RNA Function?
Order your custom AUMblock oligos today. Our AI-driven design platform will identify the optimal binding sites on your target RNA to achieve the desired steric blocking effect. We offer personalized consultation to help you select the right targeting strategy for your specific research goals.
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