micro_rna

Recent Advances in miRNA Development and Clinical Application

Authors and Affiliations

  • Sara Nunes, Laboratory of Medicine and Precision Public Health (MeSP2), Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Bahia, Brazil

  • Rana Bastos, Federal University of Bahia (UFBA), Salvador, Brazil

  • Ananda Isis Marinho, FIOCRUZ

  • Raissa Vieira, FIOCRUZ

  • Ingra Benício, FIOCRUZ

  • Maria Alícia de Noronha, UFBA

  • Sofia Lírio, Bahiana School of Medicine and Public Health, Salvador, Brazil

  • Cláudia Brodskyn, FIOCRUZ

  • Natalia Machado Tavares, FIOCRUZ (Corresponding author)

Article Info

  • Keywords: microRNAs, infectious diseases, biomarkers, therapeutic targets

Abstract

  • MicroRNAs (miRs): Small RNAs important for gene regulation emerging as candidates for biomarkers and therapeutic targets in infectious diseases.

    • MiRs help in distinguishing healthy from diseased states and different disease stages.

    • They can be detected in biological fluids, supporting non-invasive diagnostics.

  • Focus of the manuscript: To describe miRs as biomarkers and therapeutic targets, analyze miR platforms, and discuss clinical applications.

1. Introduction

  • Importance of Research: Understanding pathogen mechanisms aids in developing new strategies for disease management.

  • Role of Non-Coding RNAs: Key elements in controlling physiological and immune responses, particularly during infections.

  • Characterization of miRNAs: Unique features and functions:

    • Approximately 22 nucleotides long, regulating gene expression by degrading mRNA or repressing translation.

    • Represent 1-2% of eukaryotic genomes, regulating over 60% of human genes.

Clinical Significance of miRNAs

  • MiRNAs as biomarkers:

    • Distinguish between healthy individuals and those with diseases, identify stages, and serve as screening tools.

  • Investigated as therapeutic targets:

    • Examples include Miravirsen for hepatitis C and MRX34 for tumors.

  • MiRNAs can enhance existing treatments' efficacy or serve as standalone therapies.


2. The Biogenesis of MicroRNAs

  • Formation Steps:

    1. Primary miRNA (pri-miRNA) transcribed from DNA.

    2. Cleaved by DROSHA into precursor miRNA (pre-miRNA).

    3. Transported to the cytoplasm and cleaved by DICER into mature miRNAs.

  • Functioning Mechanism:

    • Integrates into the RNA-induced silencing complex (RISC) to regulate target mRNA expression, leading to decreased translation or degradation.

3. Clinical Applications of miRNAs

3.1 Treatment and Therapy

  • Utilization in Medicine:

    • Specific sequences known as miRNA mimics and antagomirs designed to modulate gene expression.

    • Preclinical trials crucial for evaluating effectiveness and optimizing delivery systems.

  • Notable Treatments:

    • AMT-130: Artificial miRNA for Huntington’s disease.

    • Miravirsen: Targets miR-122 to reduce HCV.

3.2 Potential of miRNAs as Biomarkers

  • Non-Invasive Diagnostic Tools:

    • Detectable in various bodily fluids, allowing for easier monitoring compared to traditional methods.

  • Highlighted Diseases: HIV, Tuberculosis, Hepatitis C, etc. with specific miRNA profiles significant for diagnosis.

  • Examples of miRNA Profiles:

    • Upregulated: miR-19a-3p in COVID-19.

    • Downregulated: miR-150 in HIV.

4. Expression of miRNAs in Infectious Diseases

4.1 Tuberculosis

  • Influence of miRNAs such as miR-21, miR-155 in modulating immune response, and phagocyte function against Mycobacterium tuberculosis.

4.2 Leprosy

  • Differential expression of miRNAs in leprosy lesions correlates with disease forms (TT and LL), showing potential for early diagnosis.

4.3 Malaria

  • Investigation into miRNAs during Plasmodium infection reveals roles in inflammation and immune response modulation.

4.4 Leishmaniasis

  • Host-cell miRNA profiling suggests modulation by Leishmania parasites, influencing immune response and persistence.

4.5 Chagas Disease

  • miRNAs like miR-145 and miR-146b play roles in modulating immune response and reducing parasitic burden.

4.6 SARS-CoV-2 (COVID-19)

  • Various miRNAs (miR-146a, miR-155, miR-2392) influence inflammatory responses and disease severity, indicating their potential as biomarkers for COVID-19 status.

5. Platforms to Analyze miRNAs

  • Overview of tools such as miRBase, TargetScan, and DIANA-microT for predicting interactions and understanding miRNA biology.

6. Obstacles and Advances in miRNA Clinical Applications

  • Challenges remain regarding effective delivery and specificity of miRNA therapies. Development of targeted delivery systems is crucial for clinical success.


7. Conclusion

  • Importance of continued research into miRNAs for their roles as biomarkers and therapeutic targets. Their inherent capabilities offer promise in treating infectious diseases and advancing personalized medicine.