# Targeting Glioblastoma with Multifunctional Anti-RAGE Oligonucleotides

> **NIH NS R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2026 · $548,395

## Abstract

PROJECT SUMMARY
 Patients diagnosed with glioblastoma (GBM) have a median overall survival of less than two years even
after receiving multimodal therapies. Multiple factors account for treatment resistance including: 1) Inability of
therapies to cross the blood-brain barrier to reach invading cells; 2) GBM’s molecular heterogeneity and
overlapping escape mechanisms that overcome targeted therapies; 3) Evasive mechanisms that render GBMs
resistant to immunotherapy. Therefore, there is an unmet need for GBM treatment approaches that address
multiple resistance mechanisms.
 The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin
superfamily, which was discovered as a transmembrane receptor for the products of nonenzymatic glycation and
oxidation of proteins. RAGE is expressed by glioma cells and is activated by ligands present in the GBM tumor
microenvironment (TME). Activation of RAGE stimulates multiple signaling pathways that promote GBM
progression. Recently, we demonstrated that genetic ablation of intracellular RAGE in gliomas inhibited multiple
oncogenic pathways that not only regulate glioma growth and invasion, but also improve the efficacy of
immunotherapies by inhibiting galactin-3 production and promoting an immunologically “permissive” TME. Based
on these observations, we propose to target RAGE as a multifaceted therapy for GBM.
 Our central hypothesis is that RAGE inactivation will suppress oncogenic pathways that are important for
GBM growth and invasion and enhance responses to immunotherapy. Three aims are proposed to test this
hypothesis. Aim 1 will optimize a multifunctional anti-RAGE oligo-based strategy to target GBM. As an alternative
approach to blocking RAGE extracellular receptor with small molecules, we propose to inhibit its signaling by
optimizing the design of anti-RAGE antisense oligos. The “scavenger” receptor property of RAGE will be
exploited to develop multifunctional oligos that are rapidly internali

## Key facts

- **NIH application ID:** 11295244
- **Project number:** 1R01NS143106-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Behnam  Badie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $548,395
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2031-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11295244

## Citation

> US National Institutes of Health, RePORTER application 11295244, Targeting Glioblastoma with Multifunctional Anti-RAGE Oligonucleotides (1R01NS143106-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/11295244. Licensed CC0.

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