In October 2024, Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their discovery of the central role of microRNA (miRNA) in gene expression. This discovery in 1993 revealed that miRNA regulates gene expression by binding to target mRNA and inhibiting its translation. Since then, the important role of miRNA in multiple gene expression pathways such as cell differentiation, proliferation and survival has gradually been recognized. However, although the biological functions of miRNA have been well studied, the road to applying miRNA in clinical treatment is still long and challenging.
miRNA: A leap from basic research to clinical application
As a short non-coding RNA, miRNA plays a vital role in many important biological processes. Early studies have found that miRNA plays an important role in the regulation of gene expression by binding to the 3' non-coding region of the target mRNA, inhibiting its translation or promoting its degradation. The discovery of miRNA provides us with a new perspective to understand the complexity of gene regulation and opens up potential therapeutic directions for disease treatment, especially in the fields of cancer, cardiovascular disease and metabolic diseases.
However, despite the great potential of miRNA in basic research, there are still many challenges in translating it into effective clinical treatment. The prospects of miRNA therapy have not yet surpassed existing treatments, and breakthroughs in multiple fields are still needed to overcome these challenges.
Two major types of miRNA therapy: miRNA mimics and antimiRs
Currently, there are two main forms of miRNA therapy: miRNA mimics and antimiRs. MiRNA mimics usually mimic the function of endogenous miRNAs and restore or enhance the function of miRNAs that are lost or downregulated in diseases. AntimiRs play a reverse role by binding to overexpressed endogenous miRNA and silencing its function.
| Cat.No. | Product Name | Price |
|---|---|---|
| MIMH0010 | miR-hsa-miR-1 mimics | Inquiry |
| MIMH0011 | miR-hsa-miR-7-1-3p mimics | Inquiry |
| MIMH0012 | miR-hsa-miR-7-2-3p mimics | Inquiry |
| MIMH0013 | miR-hsa-miR-7-5p mimics | Inquiry |
| MIMH0014 | miR-hsa-miR-9-3p mimics | Inquiry |
| MIMH0015 | miR-hsa-miR-9-5p mimics | Inquiry |
| MIMH0016 | miR-hsa-miR-10b-3p mimics | Inquiry |
| MIMH0017 | miR-hsa-miR-10a-3p mimics | Inquiry |
| MIMH0018 | miR-hsa-miR-10b-5p mimics | Inquiry |
| MIMH0019 | miR-hsa-miR-10a-5p mimics | Inquiry |
| MIMH0020 | miR-hsa-miR-15a-3p mimics | Inquiry |
MiRNA mimics and antimiRs therapy can act on multiple genes at the same time, amplifying the activation or inhibition of specific signaling pathways, and therefore have potential advantages in treating complex diseases (such as cancer, fibrosis, etc.). However, this wide range of action characteristics also brings an inevitable problem - off-target effects. Because miRNA has low targeting specificity, it may bind to multiple unrelated genes, resulting in adverse reactions or toxic effects.
The main challenges faced by miRNA therapy
(1) Difficulty in target selection and validation
The first challenge of miRNA therapy is target selection and validation. Since miRNAs can usually target multiple genes at the same time, it is extremely complicated to accurately identify their mechanism of action. At present, although more advanced algorithms, extensive sequence data, and tools such as the MiRBase database can help predict the binding sites of miRNAs and mRNAs, the functions of most miRNAs are still unclear and cannot be verified in all biological contexts.
In clinical applications, miRNA mimics are mainly used to replace missing or low-expressed miRNAs. At this time, target specificity is not the main issue. The key is how to find miRNAs that can directly affect the target pathway and prove that their restoration of activity can alleviate the disease phenotype. However, the expression of miRNAs in diseases such as tumors is highly heterogeneous and is affected by the tumor microenvironment, which makes it more difficult to find a unified miRNA that can work in multiple tumors.
(2) Off-target effects and safety
Due to the multi-target nature of miRNA, off-target effects may occur during treatment, leading to the inhibition or activation of non-target genes, thereby causing adverse reactions. For example, antimiRs therapy may target certain tumor suppressor genes or genes involved in normal cell homeostasis, which may interfere with the basic functions of cells. In addition, miRNA therapy may interact with other non-coding RNAs, further increasing the complexity of treatment.
(3) Delivery and toxicity issues
An effective delivery vehicle must not only effectively deliver miRNA to target cells, but also avoid triggering immune or toxic reactions. Although lipid nanoparticles (LNPs) and other delivery systems have achieved certain success in siRNA and mRNA vaccines, miRNA therapy still faces greater delivery challenges. In early miRNA clinical trials, although lipid nanoparticles were used for delivery, the results were not ideal. Currently, researchers are studying how to achieve more precise targeted delivery, especially tumor-targeted delivery.
miRNA as a diagnostic tool and therapeutic prospect
Although miRNA therapy still faces many challenges in clinical application, its potential as a diagnostic tool has gradually emerged. miRNA can be released from cells through exosomes and enter body fluids, which allows miRNA to be used as a biomarker in body fluids such as blood and urine for early diagnosis of diseases. For example, by analyzing the expression of miRNA in the blood, specific miRNAs can be identified that may have higher expression in cancer or other diseases or be associated with treatment response. In fact, some diagnostic tools of miRNA panels have entered clinical use and achieved initial results.
Although miRNA therapy faces many challenges, its application prospects in disease diagnosis are still bright. With a deeper understanding of the biological role of miRNA and advances in delivery and targeting technologies, miRNA is expected to occupy a place in future treatments.