Editorial - Journal of Experimental Stroke & Translational Medicine (2025) Volume 17, Issue 2
Oligonucleotide Therapies: A New Frontier in Precision Medicine
Dr. Alex Morgan*
Department of Pharmacology and Therapeutics, University of Oxford, United Kingdom
- *Corresponding Author:
- Dr. Alex Morgan
Department of Pharmacology and Therapeutics, University of Oxford, United Kingdom
E-mail: alex.morgan@pharm.ox.ac.uk
Received: 01-March-2025, Manuscript No. jestm-25-170397; Editor assigned: 3-March-2025, PreQC No. jestm-25-170397 (PQ); Reviewed: 17-March-2025, QC No. jestm-25-170397; Revised: 24-March-2025, Manuscript No. jestm-25-170397 (R); Published: 31-March-2025, DOI: 10.37532/jestm.2024.16(6).323-324
Introduction
The rapid expansion of molecular medicine has propelled oligonucleotide therapies into the spotlight as one of the most promising therapeutic strategies for genetic and rare diseases. Unlike conventional small-molecule drugs, oligonucleotide-based therapies act at the level of gene expression by targeting messenger RNA (mRNA) or non-coding RNA [1]. This enables direct modulation of disease-causing genes, paving the way for precision medicine. In recent years, several oligonucleotide drugs have gained regulatory approval, demonstrating their potential to address previously untreatable conditions.
Types of Oligonucleotide Therapies
Oligonucleotide therapeutics encompass a range of modalities, each with unique mechanisms of action:
Antisense Oligonucleotides (ASOs): ASOs are short, synthetic strands of nucleotides designed to bind complementary RNA sequences. By modulating splicing, degrading target RNA via RNase H, or blocking translation, ASOs can effectively reduce or alter protein production. Examples include nusinersen for spinal muscular atrophy [2].
Small Interfering RNAs (siRNAs): siRNAs function through the RNA interference (RNAi) pathway, guiding the RNA-induced silencing complex (RISC) to degrade specific mRNA transcripts. Approved siRNA drugs such as patisiran have shown success in treating transthyretin-mediated amyloidosis.
MicroRNA (miRNA) Modulators: Since dysregulated microRNAs contribute to several diseases, synthetic oligonucleotides can either inhibit overexpressed miRNAs (antagomirs) or mimic deficient ones, restoring normal cellular regulation.
Aptamers: Aptamers are oligonucleotides that fold into three-dimensional structures, enabling them to bind target proteins with high specificity. Pegaptanib, an aptamer targeting vascular endothelial growth factor (VEGF), was one of the earliest approved oligonucleotide drugs.
Advantages of Oligonucleotide Therapeutics
The most significant advantage of oligonucleotide therapies lies in their precision. By directly targeting genetic sequences, they minimize off-target effects and offer the possibility of treating conditions caused by single-gene mutations. Moreover, their design and synthesis are relatively rapid compared to traditional drug development, allowing faster progression from discovery to clinical testing.
Another advantage is adaptability. Oligonucleotide sequences can be reprogrammed to address different genes, making them a versatile therapeutic platform. Additionally [3], oligonucleotide therapies can be combined with other treatment modalities, including gene therapy and biologics, to enhance efficacy.
Challenges and Limitations
Despite their promise, oligonucleotide therapies face several challenges:
Delivery: Efficient delivery to target tissues remains the primary hurdle. While advances in lipid nanoparticles and conjugation strategies (such as GalNAc for liver targeting) have improved biodistribution, extrahepatic delivery remains difficult.
Stability and Immunogenicity: Unmodified oligonucleotides are prone to degradation by nucleases and may trigger immune responses. Chemical modifications help, but they must balance safety and efficacy.
Cost and Accessibility: Manufacturing complexity and regulatory requirements contribute to high treatment costs, limiting accessibility for patients in resource-limited settings [4].
Future Perspectives
The field of oligonucleotide therapeutics continues to evolve rapidly. Advances in delivery technologies, novel chemical modifications, and expanding clinical applications promise to extend their reach beyond rare diseases to common conditions such as cancer [5], cardiovascular disorders, and neurodegenerative diseases.
Moreover, ongoing research is exploring personalized oligonucleotide therapies tailored to individual genetic profiles. The approval of patient-specific “n-of-1” ASOs has already demonstrated the feasibility of ultra-personalized medicine, representing a paradigm shift in healthcare.
Conclusion
Oligonucleotide therapies represent a transformative step in modern medicine, offering precise, versatile, and innovative strategies to treat genetic and complex diseases. While challenges such as delivery and cost remain, the continued development of this therapeutic class promises to expand treatment options for patients worldwide. As technological advances accelerate, oligonucleotide therapeutics are poised to become a cornerstone of precision medicine in the decades ahead.
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