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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Precision RNA-based Gene Silencing and Theranostics Delivery Strategies for Glioma: Advances in siRNA and Emerging
Aneesh Parmar1, Amar Deep Ankalgi1, Ankit Sharma1
1Department of Pharmaceutical Analysis, Laureate Institute of Pharmacy, Kangra, Himachal Pradesh, India.
Introduction:
Gliomas, particularly Glioblastoma Multiforme (GBM), remain highly lethal despite surgery, radiotherapy, and chemotherapy, largely due to their infiltrative biology, marked molecular heterogeneity, and the restrictive Blood-Brain Barrier. RNA interference (RNAi)-based therapeutics, including Small Interfering RNA (siRNA) and emerging microRNA (miRNA)-modulating strategies, enable targeted silencing of oncogenic drivers. However, their clinical application is constrained by rapid systemic clearance, nuclease-mediated degradation, off-target effects, and inefficient brain delivery.
Objective:
This review evaluates recent advances in RNA-based precision gene silencing for glioma, with particular focus on siRNA therapeutics, emerging miRNA strategies, nanocarrier-enabled delivery systems, and theranostic integration for imaging-guided therapy.
Method:
A comprehensive literature search (1998-2026) of PubMed, Scopus, and Google Scholar was performed to identify preclinical and early clinical studies addressing glioma pathobiology, RNA interference mechanisms, siRNA targets, nanocarrier platforms, and imaging-guided theranostic systems, with emphasis on orthotopic models, registered clinical trials, and mechanistically well-characterized datasets.
Results:
Non-viral nanocarriers (lipid nanoparticles, bio-reducible polymers, dendrimer-gold, exosomes) enable siRNA protection, BBB penetration, and knockdown of EGFR, STAT3, BCL-2, VEGF, and GLUT-3 in orthotopic glioma models. Emerging miRNA-based strategies, including anti-miR-21 and miR-100 modulation, showed potential for reversing chemoresistance. Combination therapies with temozolomide/doxorubicin produced greater efficacy than single-agent approaches. Theranostic imaging platforms (PET/MRI/SPECT) enabled real-time monitoring of biodistribution and treatment responses.
Conclusion:
RNA-based theranostic strategies show promising potential for glioma therapy. However, further optimization of delivery systems, improved safety profiles, and successful clinical translation remain necessary.
Insights
RNA-based precision gene silencing offers new hope for glioma treatment by targeting oncogenic drivers. Advances in nanocarrier delivery and theranostic integration show promise, but clinical translation requires further development.
Area of Science:
- Neuro-oncology
- Molecular Therapeutics
- Biomedical Engineering
Background:
- Gliomas, including Glioblastoma Multiforme (GBM), are aggressive brain tumors with poor outcomes due to infiltrative growth, heterogeneity, and the blood-brain barrier.
- RNA interference (RNAi) therapeutics, like Small Interfering RNA (siRNA) and microRNA (miRNA) strategies, offer targeted silencing of cancer-driving genes.
- Clinical use of RNAi is limited by systemic clearance, degradation, off-target effects, and poor brain delivery.
Purpose of the Study:
- This review examines recent progress in RNA-based gene silencing for glioma.
- Focus areas include siRNA therapeutics, miRNA modulation, nanocarrier delivery systems, and theranostic applications for imaging-guided treatment.
Main Methods:
- A comprehensive literature search (1998-2026) of major scientific databases was conducted.
- Studies focused on glioma pathobiology, RNAi mechanisms, siRNA targets, nanocarriers, and theranostic systems.
- Emphasis was placed on orthotopic models, clinical trials, and well-characterized data.
Main Results:
- Non-viral nanocarriers effectively protected siRNA, facilitated blood-brain barrier penetration, and silenced key oncogenes (e.g., EGFR, STAT3) in glioma models.
- miRNA strategies (anti-miR-21, miR-100) showed potential in overcoming chemoresistance.
- Combination therapies and theranostic imaging platforms (PET/MRI/SPECT) demonstrated enhanced efficacy and treatment monitoring.
Conclusions:
- RNA-based theranostic approaches hold significant promise for advancing glioma therapy.
- Further research is needed to optimize delivery systems, enhance safety, and achieve successful clinical translation.
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