Recently, AbogenYuMolecular Therapy-Nucleic AcidsJournal Publishes Article Entitled“Development and characterization of a miRNA-responsive circular RNA expression system with cell type specificity”Research Paper,Reported its self-developed method utilizing micro...RNA（microRNA`, abbreviated as`miRNA) to enhance the circularRNAInnovative methods expressed in specific target tissues or cells demonstrate broad application prospects and great development potential.

Figure1: Screenshot of the research paper

miRNAIs a class with a length of19-24A single-stranded non-coding nucleotideRNAMolecules, which affectmRNAThe stability and translation process play an important role in regulating gene expression.2024The honor of the Nobel Prize in Physiology or Medicine was awarded toVictor AmbrosAndGary RuvkunThese two scientists,In recognition of their discoverymiRNAAnd its role in post-transcriptional gene regulation.

Figure2：2024The Nobel Prize in Physiology or Medicine awarded for the discoverymiRNAand its role in post-transcriptional gene regulation

CircularRNA（circRNA) are a unique class of single-strandedRNAMolecule, and LinearRNAIn comparison, its molecules feature a closed-loop structure, offering higher stability and resistance to degradation. However, the challenge lies in achieving cyclicRNATissue- or cell-specific expression still faces significant challenges. Based onmiRNACharacteristics of tissue- or cell-specific distribution, this study constructedmiRNAResponsive CircularRNAExpression system, successfully solved the aforementioned challenges.

miRNA-Responsive Circular RNA Expression System Offers New Avenues for Tissue-Specific Expression

The Circular of This StudyRNAThe expression system used containsmiRNAInternal Ribosome Entry Site (IRES) Binding Site (IRES）This translation element, through the combination of tissue-specificmiRNAPromote translation activation to achieve circularityRNATissue-specific expression.

First, we applymiR-122Hepatitis C virus binding site (HCV）5’Non-Translated Region (UTR) as a translation componentIRESTo construct circularRNA, which can respond to exogenousmiR-122, AchievemiR-122Protein translation activation under induction. This discovery is consistent with the generalmiRNAInhibitionmRNAThe mechanisms of expression are different, proving that miRNAVersatility in regulating gene expression.

Figure3: ContainingmiRNABinding SiteHCV 5'UTRResponsivemiRNA, achieving a circularRNATranslation Activation

Next, throughHCV 5’UTRCarry out the transformation and use othersmiRNABinding Site SubstitutionHCV 5’UTR MiddlemiR-122The combination site enables the corresponding function.miRNAInduced Translation Activation. That isBy altering the cyclicRNA In the constructmiRNA Binding sites can be determined based on different tissues or cell types.miRNAExpression profile for customizing circularRNATargeted expression, thereby enhancing efficacy while minimizing off-target risks.。

In addition, these circularRNAMolecules can also respond to a variety of cells, including tumor cells and endogenous immune cells.miRNASignals, thereby regulating circular patterns in a cell-specific mannerRNAThe level of translation.RNAThe secondary structure prediction results indicate that, miRNABinding to the target leads toHCV IRESThe conformational change induced the formation of a translation-favorable conformation, thereby promoting the expression level of downstream genes.

This study willmiRNAThe distribution and regulatory attributes of circularRNACombined with the translation, circularRNATargeted expression。This innovative approach can enhance the translation efficiency of specific organs, tissues, or cells, reduce potential off-target effects, and increase the basis forRNAThe therapeutic window of the drug, thereby expanding the cyclicRNAPotential applications of the therapy.In the future, we will continue to explore circularRNA The targeted expression capabilities for various diseases, and is committed to expanding this innovative approach to a broader range of therapeutic fields.

Innovative Technology Platform to Further Enhance the Safety and Efficacy of Nucleic Acid Drugs

Following Abogen's independent development breakthrough of overseas patent restrictions with a novel circularRNASystem ("CisSystem") Afterwards, This Study ReportsmiRNAResponsive CircularRNAThe expression system once again demonstrates the company's strong R&D strength and innovation capabilities in the field of nucleic acid drug development, relying on its innovative technology platform.miRNAResponsive CircularRNAPatents related to the expression system have also been applied for, and the company will further build up its patent barriers and lead innovation in nucleic acid drugs.

We look forward to the continuous emergence of more exciting research results based on the company's innovative technology platform in the future, further promoting the innovation of nucleic acid drugs and contributing more to the development of safer and more effective nucleic acid drugs.

Original link:Ma, Yu et al. Molecular Therapy Nucleic Acids, Volume 36, Issue 1, 102450. DOI: 10.1016/j.omtn.2025.102450

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Breaking Through Overseas Patent Barriers, Abogen Successfully Develops Circular RNA Based on Cis System

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Abogen Biosciences Co., Ltd. (Abbr. "Abogen") is an innovative biopharmaceutical company focused on the research and development of messenger ribonucleic acid (mRNA) drugs. The company owns industry-leading, proprietary intellectual property rights in mRNA and nanodelivery technology platforms. It is one of the few mRNA drug R&D enterprises in China with complete value chain capabilities, covering all aspects from mRNA design, formulation development to large-scale production. The company has established a rich product pipeline, spanning multiple fields including infectious disease prevention and control (such as the mRNA COVID-19 vaccine), cancer immunotherapy, protein replacement therapy, and more.