MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis
Abstract
:1. Introduction
2. MiRNA Nobel Prize
3. Nomenclature
4. Biogenesis
- Transcription of miRNA Genes: Most miRNAs are transcribed by RNA polymerase II (Pol II) as primary miRNAs (pri-miRNAs), several kilobases long and capped, polyadenylated, and structured with stem–loop formations. Some miRNAs, however, are transcribed by RNA polymerase III. These pri-miRNAs can originate from independent miRNA genes, protein-coding genes’ introns, or polycistronic clusters containing multiple miRNA sequences [19];
- Nuclear Processing of pri-miRNA: Once transcribed, pri-miRNAs undergo processing within the nucleus. A microprocessor complex, composed of the RNase III enzyme Drosha and its cofactor DiGeorge syndrome critical region gene 8 (DGCR8), cleaves the pri-miRNA at the stem–loop region, releasing a shorter precursor miRNA (pre-miRNA) of approximately 70 nucleotides. This cleavage step is crucial for defining the miRNA’s 5′ and 3′ ends [20];
- Nuclear Export of pre-miRNA: The pre-miRNA is then exported from the nucleus to the cytoplasm. Exportin-5, a Ran-GTP-dependent nuclear transport receptor, recognizes the double-stranded stem structure of the pre-miRNA and facilitates its export across the nuclear membrane. The high-affinity interaction between Exportin-5 and pre-miRNA ensures that only properly processed pre-miRNAs are transported out of the nucleus [21];
- Cytoplasmic Processing of pre-miRNA: Once in the cytoplasm, the pre-miRNA is further processed by the RNase III enzyme Dicer, which cleaves the loop structure of the pre-miRNA, yielding a miRNA duplex of about 22 nucleotides. Dicer partners with the trans-activator RNA-binding protein (TRBP) and Argonaute (AGO) proteins to form the RNA-induced silencing complex (RISC). One strand of the miRNA duplex, the guide strand, is predominantly loaded onto AGO proteins in RISC, while the complementary passenger strand is degraded [22];
- Functional Maturation and Targeting: The mature miRNA-RISC complex functions in gene silencing. The miRNA guides RISC to target mRNAs, where it typically binds to the 3′ UTRs of target transcripts through imperfect base-pairing. If the complementarity is high, this binding leads to either translational repression or mRNA cleavage. The extent of complementarity between the miRNA and its target determines the mode of the gene silencing [6].
4.1. Biogenesis in Plants
4.2. Evolution
5. Mechanisms of miRNA Action
- Cap-40S initiation inhibition;
- 60S ribosomal unit joining inhibition;
- Elongation inhibition;
- Ribosome drop-off (premature termination);
- Co-translational nascent protein degradation;
- Sequestration in P-bodies [44];
- MRNA decay (destabilization) by shortening its poly(A) tail;
- MRNA cleavage, where the mRNA strand is cleaved into two pieces;
- Transcriptional inhibition through microRNA-mediated chromatin reorganization, followed by gene silencing;
5.1. RNA-Induced Silencing Complex (RISC)
5.2. Mode of Silencing and Regulatory Loops
5.3. Turnover
5.4. Cellular Functions
5.5. Exosomes
6. Experimental Methods
7. Applications
7.1. Biomarkers
7.2. Cancer
7.3. Cardiovascular Diseases
7.4. Neurodegenerative Diseases
7.5. Autoimmune Diseases
7.6. Viral Infections
7.7. Alcoholism
7.8. Aging
- miR-146a: This miRNA can inhibit IL-6 and IL-1β, two key inflammatory cytokines upregulated in aged, senescent cells. Targeting these cytokines with miR-146a mimics could reduce inflammation and slow tissue degeneration;
- miR-29: This miRNA can inhibit collagen-degrading enzymes, such as matrix metalloproteinases (MMPs), that are involved in the breakdown of the extracellular matrix in aging tissues. MiR-29 mimics could maintain tissue structure and reduce fibrosis, which becomes more common with age [157];
- miR-375: This miRNA inhibits IGF-1R, a receptor in the IGF pathway that promotes growth and can contribute to age-related diseases, like cancer. Overexpression of miR-375 could reduce IGF-1R activity and help to mitigate these risks [158];
- miR-34a: This miRNA has been shown to suppress p53 and Bcl-2, proteins involved in apoptosis and stress responses, respectively. Modulating the levels of miR-34a may help to balance apoptosis in aging cells, potentially reducing unwanted cell death in key tissues, like the brain or heart [159];
- miR-103/107: These miRNAs target caveolin-1, a regulator of insulin signaling. Inhibiting these miRNAs could enhance insulin sensitivity, which typically decreases with age, helping to prevent or manage metabolic diseases [153].
7.9. Obesity
7.10. Hemostasis
7.11. Others
7.12. Plants
7.13. MiRNAs in Precision Medicine
7.14. MiRNAs in Regenerative Medicine
7.15. Synthetic Biology and miRNA-Based Therapeutics
7.16. MiRNAs in Gene Editing
7.17. Tissue-Specific miRNA
- MiR-1, miR-133, and miR-206 are known as “myo-miRs” and play crucial roles in regulating muscle development (myogenesis), differentiation, and repair [192]. They suppress genes involved in muscle atrophy and promote the growth of new muscle fibers after injury or exercise;
- MiR-1 and miR-133 are also critical in the heart for controlling cardiac muscle differentiation;
- MiR-208a and miR-499 are mainly involved in cardiac contractility and protecting the heart against hypertrophy;
- MiR-122 is liver-specific and is crucial in cholesterol and fatty acid metabolism. It is also essential for liver development and function. MiR-21 and miR-199a are involved in liver fibrosis and hepatocyte proliferation [193];
- MiR-124 is one of the most abundant miRNAs in the brain and is involved in neuronal differentiation and neuroprotection;
- MiR-9 helps to regulate neurogenesis, while miR-132 and miR-128 are essential for synaptic plasticity and cognitive function;
- MiR-143 and miR-103 regulate adipocyte differentiation and insulin sensitivity, making them necessary in fat metabolism and energy homeostasis. MiR-155 is involved in inflammatory regulation within adipose tissue;
- MiR-375 is crucial for insulin secretion and pancreatic beta cell function. It regulates glucose homeostasis and pancreatic cell differentiation, contributing to overall metabolic health;
- MiR-192 and miR-194 are essential for kidney development and maintaining nephron integrity;
- MiR-29 and miR-21 are involved in kidney fibrosis and injury response, playing critical roles in kidney diseases;
- MiR-21 and miR-126 are involved in lung development, inflammation, and repair processes, particularly during fibrosis;
- MiR-29b regulates collagen deposition and is essential in lung fibrotic disorders. MiR-26a, miR-29b, and miR-214 play critical roles in bone development by regulating osteoblast differentiation and bone formation. These miRNAs are targets for promoting bone repair and regeneration;
- MiR-203 and miR-205 regulate keratinocyte differentiation, maintain skin integrity, and promote wound healing. MiR-31 supports epidermal proliferation and repair after injury;
- MiR-150, miR-155, and miR-223 are critical regulators in hematopoietic cells, controlling the differentiation of immune cells and playing roles in inflammation and immune responses;
- MiR-210 and miR-141 regulate placental development and adaptation to hypoxia;
- MiR-517 is involved in trophoblast function and placental growth;
- MiR-34c and miR-449a are involved in spermatogenesis and regulating Sertoli and Leydig cells;
- MiR-202 plays a role in male fertility and testicular development.
7.18. Targeted Delivery Using Tissue-Specific Promoters
7.18.1. Ligand-Conjugated Nanoparticles for Receptor-Mediated Targeting
7.18.2. Cell-Penetrating Peptides (CPPs)
7.18.3. Aptamers for Cell-Specific Targeting
7.18.4. Virus-Like Particles (VLPs) for Tissue-Specific Targeting
7.18.5. Lentiviruses and Retroviruses
7.18.6. CRISPR/Cas9 and Aptamers for Enhanced Targeting
7.18.7. CRISPR-Based miRNA Activation Systems
8. Delivery
8.1. Ex Vivo Manipulation
8.2. In Vivo Administration
8.3. Course of Action
- Delivery System: If delivered via nanoparticles, liposomes, or viral vectors, the miRNA may be protected from immediate degradation, allowing for it to stay active longer. However, nucleases in the bloodstream or tissues rapidly degrade miRNAs delivered without protection;
- Tissue Type: Different tissues have varying miRNA turnover rates. For example, miRNAs in the liver quickly degrade because of high metabolic activity, while miRNAs in the brain or muscle may last longer because of different enzymatic environments;
- Endosomal Escape: For the miRNA to be active, it must escape the endosome after cellular uptake. If the delivery system is inefficient at facilitating endosomal escape, the miRNA may be degraded within the cell before it can act on its target mRNA;
- Half-life of MiRNA: Endogenous miRNAs typically have a half-life of 12–24 h, varying depending on the cellular environment. Synthetic miRNA mimics may be modified to enhance stability, but they still typically exhibit transient effects unless continuously delivered.
- Stable Expression Vectors: In ex vivo manipulation, miRNAs can be introduced using viral vectors (e.g., lentiviruses or AAVs) that integrate into the host cell’s genome, enabling continuous miRNA expression after the cells are transplanted back into the patient. In this case, the host cells would produce the miRNA indefinitely, offering a permanent or long-term solution;
- Lentiviral vectors, which integrate into the genome, can install miRNAs permanently in dividing cells, such as those in the liver or blood. However, this approach risks insertional mutagenesis (disruption of essential genes), making it less ideal for permanent in vivo miRNA therapy unless particular targeting strategies are employed;
- CRISPR-Based MiRNA Activation: Another ex vivo approach involves using CRISPR-based gene editing to permanently activate or repress specific miRNA genes within a cell’s genome. This would ensure the miRNA remains permanently active in the cells reintroduced to the patient. CRISPR/Cas9-based gene editing offers a theoretical path toward permanent miRNA installation in vivo. Using CRISPR/Cas9 to activate or repress the expressions of endogenous miRNAs directly, it may be possible to modulate miRNA expression within specific tissues permanently. For instance, CRISPRa (CRISPR activation) can upregulate the expressions of miRNAs that promote beneficial effects, such as those involved in muscle regeneration or cardioprotection. This approach would include delivering the CRISPR machinery and the guide RNA to specific tissues;
- Similarly, CRISPRi (CRISPR interference) can permanently repress miRNAs that cause harmful effects, such as miRNAs that promote fibrosis or inflammation. CRISPR can be delivered in vivo using lipid nanoparticles, plasmids, or other delivery vehicles that allow for the Cas9 protein and guide RNA (gRNA) to target specific cells, creating a permanent change in the genome. This approach provides a potential long-term solution for genetic diseases or tissue-specific modifications.
8.4. Synthetic mRNA Therapy with Self-Amplifying Systems
8.5. Non-Viral Gene Therapy Systems for Long-Term Expression
- Immune Response: One major challenge with permanent in vivo miRNA expression is the risk of triggering an immune response. Viral and non-viral delivery systems may activate the immune system, leading to vector clearance or potential damage to the host tissue. This is particularly relevant for viral vectors that persist in the body for long periods;
- Insertional Mutagenesis: If miRNA constructs are delivered using integrating viral vectors (such as lentiviruses), there is a risk of insertional mutagenesis, where the viral genome integrates into a critical region of the host’s genome, potentially disrupting essential genes and causing adverse effects, including cancer;
- Unintended Off-Target Effects: Permanently installing miRNA in a tissue could lead to off-target gene regulation, where the miRNA affects genes beyond the intended target. Although miRNAs are generally specific, they can target multiple genes, which raises the possibility of unintended consequences over the long term.
8.6. Nanoparticle-Based Delivery (Repeated Administration)
8.7. Cell-Based Therapies
9. Discovery
- Isolate the total RNA from the tissue or cells of interest;
- Use specialized protocols to enrich small RNAs, including miRNAs (typically using size-selection methods);
- Prepare a small RNA library from the isolated RNA by ligating specific adapters to the 5′ and 3′ ends of small RNAs;
- Perform high-throughput sequencing on the small-RNA library. This generates millions of short reads corresponding to small RNAs present in the sample;
- Align the sequenced reads to the reference genome to identify known and potentially new miRNAs. Novel miRNAs can be identified by detecting sequences that match the criteria for miRNA precursor structures (such as the formation of a hairpin secondary structure);
- Once candidate miRNAs are identified through sequencing, northern blotting can be used to validate their expressions. This method detects small RNA molecules based on size and allows researchers to confirm the presence and abundance of a novel miRNA in a specific tissue or developmental stage;
- QPCR can be used to confirm the expression levels of newly discovered miRNAs.
- The presence of hairpin structures in precursor miRNAs (pre-miRNAs);
- The conservation of sequences across species;
- The minimum free energy (MFE) of the predicted secondary structure to determine if it will likely form a stable hairpin.
- miRDeep: A widely used algorithm that identifies novel miRNAs by aligning small-RNA reads to the genome and predicting precursor structures;
- miRBase: A comprehensive miRNA database that includes information on known miRNAs and can be used to cross-check potential novel miRNAs;
- RNAfold: A tool used to predict the secondary structure of RNA sequences, helping to determine if a candidate sequence forms a stable hairpin structure typical of miRNA precursors.
9.1. Comparative Genomics
- Align sequences from closely related species to find conserved regions of small RNAs;
- Analyze the conservation of the predicted secondary structures of the miRNA precursors.
9.2. Machine-Learning Models
10. Regulatory Process
11. Challenges and Limitations
11.1. Off-Target Effects and Immune Responses
11.2. MiRNA Stability and Degradation
12. Intellectual Property
Examples of miRNA Patents
13. Commercial Products
14. Conclusions
- miRNA Rejuvenation of Therapeutic Protein Expression: In therapeutic protein production, controlling the consistent and long-term expressions of proteins, especially in cases like gene therapies, is essential for achieving a sustained therapeutic effect. miRNAs could be used to rejuvenate or regulate the expressions of proteins significantly when their production naturally declines because of aging or disease [252];
- Enhancing Protein Expression in Aging Tissues: Aging often leads to a decline in the production of key proteins, which can contribute to diseases, such as sarcopenia, neurodegeneration, and metabolic disorders. MiRNA therapy could be designed to rejuvenate these therapeutic proteins’ expressions by suppressing protein production inhibitors or activating the necessary transcription factors. For example, the downregulation of miR-34a, which is associated with aging, could be employed to increase the expression of sirtuins (proteins involved in longevity and metabolism) or factors that promote muscle regeneration, like IGF-1 (insulin-like growth factor) [253];
- Controlling Protein Production in Gene Therapy: Ensuring that the therapeutic gene is expressed at the right time and in the right amount is crucial. MiRNA-based systems could precisely control protein expression by designing synthetic miRNA circuits that respond to environmental or cellular signals. For instance, miRNA switches could be used to control the expression of therapeutic proteins only when needed, reducing side effects and improving the overall safety profile of gene therapies. This could be particularly beneficial in conditions requiring intermittent treatment, such as intermittent hormone deficiencies or enzyme replacement therapies [254];
- miRNAs in Enhancing Protein Stability and Folding: miRNAs can be used to regulate chaperone proteins involved in folding therapeutic proteins. In cystic fibrosis, the correct folding of proteins is critical, and mutations can lead to misfolding. MiRNA-based therapies could target pathways that enhance the production of molecular chaperones, improving the folding and function of therapeutic proteins [255];
- MiRNA-Based Vaccines: Vaccines are traditionally designed to elicit immune responses against specific pathogens by presenting the body with an antigen (such as a weakened virus or protein subunits) [256]. However, miRNA technology could open new frontiers in vaccine development, offering several advantages, including enhanced specificity, long-lasting immune responses, and the potential to create personalized vaccines. One of the most exciting applications of miRNA technology in vaccines involves creating vaccines that induce host cells to produce antigens from within. By designing a vaccine that introduces miRNAs targeting viral RNA or mRNA encoding viral proteins, host cells can produce specific viral antigens, stimulating the immune system more naturally. This approach could benefit rapidly mutating viruses, such as influenza or SARS-CoV-2. A synthetic miRNA-based vaccine could target conserved regions of the viral genome, minimizing the effects of viral mutations. This would provide longer-lasting immunity and eliminate the need for frequent updates to vaccine formulations. Cancer vaccines stimulate the immune system to recognize and attack tumor-specific antigens. MiRNA technology could enable the creation of personalized cancer vaccines by targeting tumor-specific mutations.
- Tumors often downregulate or mutate proteins that suppress tumor growth, such as p53, or proteins that would usually alert the immune system to cancerous cells. MiRNA-based vaccines could enhance the expression of these proteins in tumor cells, increasing the likelihood that the immune system will detect and destroy them [257]. Another futuristic application is using miRNAs to boost the presentation of antigens in traditional vaccines. Antigen-presenting cells (APCs) play a crucial role in the immune response by displaying antigens to T-cells. MiRNAs could enhance these cells’ function by upregulating key pathways involved in antigen processing and presentation. For instance, miR-155 is involved in immune cell activation, and its upregulation could enhance the effectiveness of vaccine-induced immune responses. By co-delivering miRNAs that boost antigen presentation with traditional vaccines, it may be possible to create vaccines that provide more robust, longer-lasting immunity [258];
- miRNA in Plant-Based Vaccines: MiRNAs could also play an essential role in producing plant-based vaccines, which use plants to produce antigens that can be administered orally or through traditional injection. Researchers could enhance the yield and stability of antigen production in plants by manipulating miRNAs in plant systems. For example, miRNAs that regulate protein synthesis or stress responses in plants could be targeted to increase the efficiency of vaccine antigen production in edible crops, such as lettuce or tomatoes. This approach could pave the way for inexpensive and easily scalable vaccines suitable for global use, particularly in resource-limited settings [259].
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Type of RNA | Function | Percentage of RNA | Nobel Prize Details |
---|---|---|---|
RNA Discovery | Enzyme polynucleotide phosphorylase is responsible for RNA synthesis. | -- | 1959: For discovering the mechanisms of RNA and DNA synthesis |
Messenger RNA (mRNA) | Serves as the template for protein synthesis during translation | 1–5% | 1961 Nobel Prize in Physiology or Medicine to François Jacob and Jacques Monod for discovering mRNA’s role in protein synthesis |
Transfer RNA (tRNA) | Carries amino acids to the ribosome during translation | 10–15% | 1968 Nobel Prize in Physiology or Medicine to Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg for their interpretation of the genetic code and its function in protein synthesis, including tRNA discovery |
RNA as a Catalyst | Catalysis function of RNA | n/a | 1989: Sidney Altman and Thomas R. Cech for discovering that RNA can act as a catalyst, leading to the understanding of ribozymes |
Small Nuclear RNA (snRNA) | Involved in the splicing of pre-mRNA by forming the spliceosome complex | <0.1% | 1993 Nobel Prize in Physiology or Medicine to Richard J. Roberts and Phillip A. Sharp for discovering split genes and RNA splicing involving snRNA |
Small Interfering RNA (siRNA) | Involved in RNA interference, degrading complementary mRNA to regulate gene expression; primarily involved in defense against viruses | <0.1% | 2006 Nobel Prize in Physiology or Medicine to Andrew Fire and Craig Mello for discovering RNA interference (RNAi), of which siRNA is a significant component |
Ribosomal RNA (rRNA) | Forms the structural and catalytic components of ribosomes, essential for protein synthesis | 80–90% | 2009 Nobel Prize in Chemistry to Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada E. Yonath for studies of the structure and function of the ribosome |
CRISPR-Cas9 using RNA | Gene-editing technology using RNA to guide DNA modification | n/a | 2020: Jennifer A. Doudna and Emmanuelle Charpentier for developing CRISPR-Cas9, a gene-editing technology |
MicroRNA [1] | It regulates gene expression by binding to target mRNAs and promoting their degradation or inhibiting translation. | <0.1% | 2024 Nobel Prize in Physiology or Medicine to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in posttranscriptional gene regulation, revealing a new layer of gene regulation that impacts development and disease |
Long Noncoding RNA (lncRNA) | Regulates gene expression at various levels, including chromatin remodeling, transcription, and posttranscriptional processing | <1% | No Nobel Prize directly for lncRNA, though it is a rapidly evolving field. |
Circular RNA (circRNA) | Acts as an miRNA sponge and may regulate gene expression; it is stable because of its circular structure. | <1% | No Nobel Prize is related to circRNA yet, but research is ongoing and rapidly evolving. |
Piwi-Interacting RNA (piRNA) | Protects the germline by silencing transposable elements; mainly found in reproductive cells | Variable, from <1% to higher than 1% | No Nobel Prize specific to piRNA, but RNA-interference-related discoveries were recognized by the 2006 Nobel Prize. |
Small Nucleolar RNA (snoRNA) | Guides chemical modifications of other RNAs, particularly rRNA | <0.1% | No Nobel Prize was specific to snoRNA, but it was linked to rRNA function, and it was recognized by the 2009 Nobel Prize in Chemistry for ribosome research. |
Antisense RNA (asRNA) | Inhibits gene expression by binding to complementary mRNA, preventing translation or inducing degradation | <0.1% | There is no Nobel Prize specifically for antisense RNA, but the field of RNA-based gene silencing has greatly expanded based on earlier work on RNA interference. |
Database Name | Hyperlink | Description |
---|---|---|
miRBase | https://www.mirbase.org/ (accessed on 12 October 2024) | A primary miRNA sequence database that provides annotations, references, and information about miRNA families |
miRTarBase | https://mirtarbase.cuhk.edu.cn/ (accessed on 12 October 2024) | Contains information on experimentally validated miRNA–target interactions compiled from the literature |
TargetScan | https://www.targetscan.org/ (accessed on 12 October 2024) | Provides predicted miRNA targets based on conserved binding sites and includes information about miRNA conservation |
miRDB | http://mirdb.org/ (accessed on 12 October 2024) | A database for predicted miRNA targets using a machine learning approach, with options to query miRNA functions |
DIANA-miRPath | http://diana.imis.athena-innovation.gr/DianaTools/index.php (accessed on 12 October 2024) | Provides pathway-based miRNA functional analysis by linking miRNA target genes to known pathways |
HMDD (Human MicroRNA Disease Database) | https://www.cuilab.cn/hmdd (accessed on 12 October 2024) | A manually curated database that collects miRNA–disease associations from the scientific literature |
miRGator | http://mirgator.kobic.re.kr/ (accessed on 12 October 2024) | An miRNA analysis tool that integrates expression data, functional annotation, and predicted targets |
miREnvironment | https://www.tools4mirs.org/ (accessed on 12 October 2024) | Focuses on miRNA–environment interactions, allowing users to explore how miRNAs are affected by environmental factors |
mir2Disease | http://www.mir2disease.org/ (accessed on 12 October 2024) | A curated database that links miRNAs to various human diseases based on experimental evidence |
OncomiRDB | http://lifeome.net/database/oncomirdb/ (accessed on 12 October 2024) | A specialized database that focuses on miRNAs implicated in cancer biology and therapeutics |
miRCancer | http://mircancer.ecu.edu/ (accessed on 12 October 2024) | Focuses on miRNAs and their involvement in various types of cancer, with data on expression and regulation |
miRGeneDB | https://mirgenedb.org/ (accessed on 12 October 2024) | A database providing curated annotations of miRNA genes across different species, focusing on high-quality annotations |
Criteria | Ex Vivo Manipulation | In Vivo Administration |
---|---|---|
Precision and Control | High degree of precision and control because of manipulation in a lab setting | Less control: delivery systems face challenges in targeting specific tissues. |
Safety and Off-Target Effects | There is a lower risk of off-target effects; cells are screened before reintroduction. | Higher risk of off-target effects and immune responses due to systemic delivery |
Efficiency and Practicality | It is time consuming, expensive, and more challenging to scale for large populations. | Faster and more accessible to administer; more practical for large-scale applications |
Applications | Best for cell-based therapies, regenerative medicine, and personalized treatments | Suitable for systemic diseases, cancer therapy, and infectious diseases |
Regulus Therapeutics |
RG-012: An miRNA inhibitor targeting miR-21, developed for treating Alport syndrome, a genetic kidney disease. It is currently in Phase II clinical trials. |
RG-125 (AZD4076): Developed in collaboration with AstraZeneca, targeting miR-103/107 to treat non-alcoholic fatty liver disease (NAFLD) |
miRagen Therapeutics |
Cobomarsen (MRG-106): An anti-miR-155 therapy targeting cutaneous T-cell lymphoma (CTCL); it has reached Phase II clinical trials. |
Remlarsen (MRG-201): An miRNA mimic of miR-29, designed to prevent fibrotic diseases, such as pulmonary and skin fibrosis |
Alnylam Pharmaceuticals |
Onpattro (Patisiran): An FDA-approved siRNA-based transthyretin-mediated amyloidosis (ATTR) therapy |
ALN-PCSsc: An experimental therapy targeting PCSK9 for hypercholesterolemia. |
Dicerna Pharmaceuticals |
DCR-PHXC is an RNAi therapeutic targeting HAO1 for primary hyperoxaluria in Phase III trials. |
DCR-HBVS: An RNAi therapeutic for hepatitis B (HBV) in Phase I/II trials |
Santaris Pharma (now a part of Roche) |
Santaris developed miravirsen (SPC3649), an anti-miR-122 therapy for Hepatitis C. It was among the first miRNA-based therapies to enter clinical trials, reaching Phase II. |
Rosetta Genomics |
Diagnostic tools using miRNA biomarkers; its miRview® assays are used for the diagnosis of cancers, like lung cancer and mesothelioma. |
MiRXES |
GASTROClear, an miRNA biomarker assay for the early detection of gastric cancer. This diagnostic tool has been commercialized in Asia and is considered as a leading non-invasive test for gastric cancer screening. |
Gene Signal |
Aganirsen is an anti-miR-21 therapy aimed at treating ocular neovascularization, a process involved in diseases like age-related macular degeneration. |
Hummingbird Bioscience |
HMBD-001: This product targets HER3-driven cancers, utilizing RNA interference (RNAi) technology, which modulates gene expression through siRNA or miRNA. This is currently in the preclinical stage. |
Storm Therapeutics |
STC-15: An RNA-based therapy targeting specific miRNAs involved in cancer progression. This product is still in the preclinical development stage. |
Marina Biotech |
CEQ508: This is an miR-34 mimic designed to treat familial adenomatous polyposis (FAP), a condition that increases the risk for developing colorectal cancer. It is currently in Phase I clinical trials. |
Silence Therapeutics |
SLN360: This product is designed to target lipoprotein(a), a known risk factor for cardiovascular diseases, using siRNA-based gene-silencing technology. It is currently in Phase I clinical trials. |
Viridian Therapeutics |
VRDN-001: This siRNA-based therapy is in the preclinical phase and aims to treat autoimmune diseases, such as thyroid eye disease, by modulating RNA pathways. |
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Niazi, S.K.; Magoola, M. MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis. Int. J. Mol. Sci. 2024, 25, 12883. https://doi.org/10.3390/ijms252312883
Niazi SK, Magoola M. MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis. International Journal of Molecular Sciences. 2024; 25(23):12883. https://doi.org/10.3390/ijms252312883
Chicago/Turabian StyleNiazi, Sarfaraz K., and Matthias Magoola. 2024. "MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis" International Journal of Molecular Sciences 25, no. 23: 12883. https://doi.org/10.3390/ijms252312883
APA StyleNiazi, S. K., & Magoola, M. (2024). MicroRNA Nobel Prize: Timely Recognition and High Anticipation of Future Products—A Prospective Analysis. International Journal of Molecular Sciences, 25(23), 12883. https://doi.org/10.3390/ijms252312883