Biochimica et biophysica acta. Reviews on cancerDec 22, 2025

Using tiny particles to deliver RNA specifically to the brain

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

RNA therapies may offer new strategies to treat aggressive brain cancers like glioblastoma and medulloblastoma, but require improved delivery methods across the blood-brain barrier.

The blood-brain barrier poses significant challenges for treating central nervous system disorders.
RNA and CRISPR gene therapies target previously inaccessible pathways, potentially transforming brain cancer treatment.
Enhanced drug transport methods, including nanoparticles, are essential for the effective delivery of RNA therapies.
Lipid nanoparticles and viral vectors are currently the most promising for clinical application in brain cancer.
Targeting strategies and non-invasive delivery techniques, such as focused ultrasound, are crucial for overcoming blood-brain barrier limitations.

Simplified

The blood-brain barrier (BBB) presents a critical challenge in treating central nervous system (CNS) disorders, particularly aggressive brain cancers such as glioblastoma (GBM) and medulloblastoma (MB). RNA therapies exploit endogenous cellular machinery to modulate gene expression, targeting previously undruggable pathways. RNA and CRISPR gene therapies hold transformative potential for brain cancer but demand breakthroughs for enhanced drug transport across the BBB. While clinical achievements in non-CNS diseases validate their efficacy, interdisciplinary collaboration is essential to advance nanoparticles (NPs) engineering, immune evasion, and non-invasive delivery for CNS applications. NPs are indispensable for advancing RNA therapies in brain cancer, with lipid nanoparticles (LNPs) and viral vectors leading clinical translation. Innovations in targeting (e.g., GLUT1, RVG peptide, ApoE mimetic peptide) and non-invasive delivery (e.g., focused ultrasound) are critical to overcome the BBB limitations. This review highlights the different strategies that can be utilized to deliver RNA-based therapies to the brain and summarizes the recent clinical efforts to deliver the RNA.

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Competing interests

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ram I Mahato reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. Ram I Mahato reports a relationship with University of Nebraska Medical Center that includes: employment and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Using tiny particles to deliver RNA specifically to the brain

Abstract

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Competing interests

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