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Antisense oligonucleotides: targeting oncogenic long non-coding RNAs for cancer therapy
Hamed Irandoost1,2, Mahdieh Mondanizadeh3, Elahe Irandoost4
1Division of Laboratory Hematology and Blood Banking, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Purpose:
This narrative review aims to summarize current evidence on antisense oligonucleotide (ASO)-based strategies targeting oncogenic long non-coding RNAs (lncRNAs) and to evaluate their therapeutic potential in cancer initiation, progression, metastasis, and treatment resistance.
Methods:
A narrative review of preclinical studies was conducted, focusing on ASO-mediated silencing of cancer-associated lncRNAs, including MALAT1, PVT1, NEAT1, and other emerging lncRNAs, across multiple malignancies such as lung, breast, ovarian, gastrointestinal, and head-and-neck cancers. Advances in ASO chemical design and delivery strategies-including lipid and polymeric nanoparticles, ligand-directed conjugates, peptide-based carriers, and gymnotic uptake-were also examined.
Results:
Preclinical evidence consistently demonstrates that lncRNA-targeted ASOs effectively suppress tumor growth, invasion, metastasis, and chemoresistance while promoting apoptosis. Improvements in ASO chemical modifications and delivery platforms have significantly enhanced ASO stability, biodistribution, and intracellular uptake, thereby improving therapeutic efficacy across diverse cancer models.
Conclusion:
Targeting oncogenic lncRNAs using ASO-based approaches represents a promising and rapidly evolving strategy in precision oncology. Although substantial progress has been achieved in ASO design and delivery, further optimization and well-structured clinical trials are required to facilitate the translation of these therapies into routine cancer treatment.
Insights
Antisense oligonucleotides (ASOs) targeting oncogenic long non-coding RNAs (lncRNAs) show significant promise in preclinical cancer models. These ASO-based strategies effectively inhibit tumor growth, metastasis, and resistance, advancing precision oncology.
Area of Science:
- Oncology
- Molecular Biology
- RNA Therapeutics
Background:
- Long non-coding RNAs (lncRNAs) play critical roles in cancer initiation, progression, metastasis, and treatment resistance.
- Targeting oncogenic lncRNAs presents a novel therapeutic avenue in precision oncology.
Purpose of the Study:
- To review current evidence on antisense oligonucleotide (ASO)-based strategies targeting oncogenic lncRNAs.
- To evaluate the therapeutic potential of these ASO strategies in various aspects of cancer.
Main Methods:
- A narrative review of preclinical studies was performed.
- Focused on ASO-mediated silencing of key cancer-associated lncRNAs (e.g., MALAT1, PVT1, NEAT1).
- Examined advances in ASO chemical design and delivery strategies (nanoparticles, conjugates, carriers).
Main Results:
- ASO-targeted lncRNAs demonstrated effective suppression of tumor growth, invasion, metastasis, and chemoresistance in preclinical models.
- ASO chemical modifications and delivery platforms enhanced stability, biodistribution, and intracellular uptake.
- Therapeutic efficacy was improved across diverse cancer models, including lung, breast, ovarian, and gastrointestinal cancers.
Conclusions:
- ASO-based targeting of oncogenic lncRNAs is a promising and rapidly evolving strategy in precision oncology.
- Significant progress in ASO design and delivery has been achieved.
- Further optimization and clinical trials are necessary for translating these therapies into routine cancer treatment.
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