Author(s) :

Sofia Geambazi.

Volume/Issue :

Abstract :

This review evaluates CRISPR-Cas13 as an RNA-targeting strategy to eradicate glioblastoma stem cells (GSCs) by knocking down transcripts that sustain self-renewal (e.g., SOX2, c-MYC, EGFRvIII, OLIG2). It focuses on guide design, delivery across the BBB to hypoxic/perivascular GSC niches, and preclinical endpoints that predict reduced recurrence. Glioblastoma Multiforme (GBM) is the most aggressive cancer of the brain, largely due to recurrence driven by Glioblastoma Stem Cells (GSCs). Treatment failure arises from interrelated factors such as therapy resistance, blood-brain barrier (BBB) impermeability, and immune evasion. CRISPR-Cas13 is a novel RNA-targeting system that directly silences key oncogenic transcripts of GSCs such as SOX2, c-MYC, and HIF-1α. Cas13 enables allele specific targeting, and a reduced risk of genomic integration compared to other genetic tools including RNA-interference (RNAi), antisense oligonucleotides (ASOs), and Cas9. However, effective delivery remains challenging as viral vectors, non-viral vectors, and exosomes each offer distinct trade-offs. Combination strategies such as pairing Cas13 with immune checkpoint inhibitors (ICIs) may overcome immune suppression and barriers posed by oncogenic drivers. In the near-term, lipid nanoparticles (LNPs) with BBB-penetrating ligands are a promising approach for GBM treatment via GSC targeting, however as the engineering of exosomes develops, their natural origins, high biocompatibility and ease of integration into difficult tissues such as the brain becomes increasingly favorable. Ultimately, advances in Cas13 engineering and delivery could enable durable GSC targeting and transform the clinical outlook for GBM patients.