# New Player in the Field of Glioblastoma Therapy: EGFRvIII-Specific Gol1 Aptamer Shows a Great Therapeutic Potential

## TL;DR

A new DNA aptamer called Gol1 shows strong potential for treating glioblastoma by targeting a specific receptor and inducing cell death.

## Contribution

The study introduces a stabilized, EGFRvIII-specific aptamer, Gol1, with superior antiproliferative and diagnostic potential for glioblastoma.

## Key findings

- Gol1 aptamer shows exceptional binding affinity for EGFRvIII and induces complete cell death in tumor cells.
- Transcriptomic analysis reveals a dual mechanism of neuronal differentiation activation and splicing factor suppression by Gol1.
- In vivo, Gol1 accumulates selectively in tumor tissue, especially at the invasive border zone.

## Abstract

Background: This study aimed to develop a superior aptamer-based therapeutic for targeted glioblastoma intervention by conducting a comparative analysis of two DNA aptamers: the original U2 sequence, selected against glioblastoma cells exhibiting high EGFRvIII expression, and its modified, shortened, and stabilized variant, Gol1. Methods: The effects of the investigated aptamers on primary human glioblastoma cells with graded receptor expression levels and on a rat 101/8 glioblastoma tissue model were rigorously studied. Results: The results demonstrated the significant superiority of the stabilized Gol1 aptamer, which exhibited exceptional binding affinity for the EGFRvIII receptor. Pronounced antiproliferative and antimigratory effects against EGFRvIII-positive human tumor cells, ultimately inducing complete cell death. Transcriptomic analysis revealed a sophisticated dual mechanism of action for Gol1: the specific activation of neuronal differentiation genes concurrent with the suppression of key alternative splicing factors. Crucially, in vivo confirmation showed highly selective accumulation of the FAM-labeled Gol1 aptamer exclusively within tumor tissue, with a maximum concentration gradient observed in the invasive border zone and a complete absence of accumulation in intact brain parenchyma. Conclusions: These comprehensive findings confirm that the Gol1 aptamer constitutes a highly promising and versatile platform for developing novel targeted theranostic strategies against glioblastoma, offering a precise approach for both diagnostic imaging and therapeutic intervention.