# The Role of CRISPR and Its Therapeutic Applications in Glioblastoma

## TL;DR

This review explores how CRISPR/Cas9 technology can be used to treat glioblastoma, a deadly brain tumor, by targeting key genetic mutations and improving delivery methods.

## Contribution

The paper provides a comprehensive overview of CRISPR's therapeutic potential and challenges in glioblastoma treatment.

## Key findings

- CRISPR/Cas9 can target key genes like EGFR, PTEN, and TP53 involved in glioblastoma progression.
- Delivery methods such as lipid nanoparticles and DNA nanostructures are advancing CRISPR's clinical feasibility.
- Off-target effects and blood–brain barrier penetration remain major challenges for CRISPR-based therapies.

## Abstract

Glioblastoma multiforme (GBM) remains the most aggressive and treatment-refractory form of primary brain tumor in adults, characterized by rapid proliferation, intratumoral heterogeneity and resistance to current therapies. Despite therapeutic advancements in surgical resection, radiotherapy and chemotherapy, clinical outcomes remain poor, underscoring the need for innovative molecular strategies. This review examines the therapeutic potential of CRISPR/Cas9 genome-editing technologies in GBM, highlighting their ability to model, dissect and potentially correct the genetic alterations that drive GBM tumorigenesis. Key molecular targets, such as EGFR, PTEN, TP53, NF1 and PIK3CA, are discussed within the context of GBM’s mutational and signaling landscape. We further outline emerging CRISPR applications in preclinical models, the current status of CRISPR-based clinical trials and the major barriers hindering translation, including off-target effects, immunogenicity and the challenge of delivering gene-editing systems across the blood–brain barrier. Particular emphasis is placed on delivery technologies, viral and non-viral vectors, including lipid nanoparticles, polymeric systems, inorganic nanocarriers and DNA nanostructures, which are rapidly evolving to improve precision, safety and CNS penetrance. Collectively, this review highlights CRISPR/Cas9 as a powerful tool whose integration with molecular neuro-oncology and precision medicine may ultimately shift GBM treatment toward more personalized and durable therapeutic interventions.