Eradicating the Root of Cancer: Targeted Therapy of Cancer Stem Cells via Exosomal DNA Delivery Presenter

Overview:

This project presents a transformative, non-viral therapeutic platform designed to selectively eliminate drug-resistant cancer stem cells (CSCs) in glioblastoma multiforme (GBM) using engineered exosomes. Developed by Dr. Kiminobu Sugaya (Professor & Head of Neuroscience, University of Central Florida), the platform overcomes two major clinical barriers in GBM treatment: (1) resistance to standard therapies caused by CSCs, and (2) poor drug delivery across the blood–brain barrier (BBB).

Key Features:

• NANOG-targeted gene therapy: Uses shRNA/DNA constructs to suppress NANOG, a key transcription factor driving CSC resistance, recurrence, and tumorigenesis.

• Exosomal Localization Signal (ELS): Proprietary sequence that enables efficient, endogenous packaging of therapeutic nucleic acids into exosomes without electroporation.

• Brain-Homing Peptide (BHP): Genetically encoded membrane peptide that enables exosomes to cross the BBB and home to tumor sites in the brain.

• Non-viral, biocompatible DDS: Avoids the toxicity and immunogenicity of viral vectors and lipid nanoparticles.

• Versatile delivery routes: Demonstrated efficacy via intravenous, subcutaneous, and intranasal administration.

Preclinical Achievements:

• Validated NANOG knockdown enhances temozolomide (TMZ) sensitivity in CSCs derived from GBM patient tissue.

• Demonstrated BBB penetration and targeted brain delivery in murine models using BHP-expressing exosomes loaded with functional cargo (e.g., GFP, RFP).

• Completed in vitro testing on 26 primary GBM-CSC lines and confirmed in vivo tumor accumulation in xenograft models.

• Developed scalable, automated exosome manufacturing system in collaboration with a leading materials company.

• Co-developing clinical-grade, serum-free, xeno-free culture media with a bioprocess media partner to ensure regulatory alignment and GMP compliance.

Applications & Expansion Potential:

• Primary target: Glioblastoma multiforme (GBM)

• Expansion to other solid tumors with NANOG overexpression (e.g., ovarian, breast, liver, colorectal)

• Broader use in neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s) and infectious disease therapies (e.g., HIV, COVID-19) using the exosome platform for targeted gene delivery

Partnering Opportunities:

We are seeking co-development partners, clinical collaborators, and strategic investors to accelerate IND-enabling studies and transition into Phase 1/2a clinical trials.

Licensing opportunities are also available for our exosome engineering technologies and NANOG-targeted therapeutics.

IP Status:

• JP5220103834 (granted): Exosomal DNA drug delivery

• US11,193,174 B2: Exosomal NANOG DNA as biomarker

• US20230212566A1: Gene modulation via exosomes

• Additional filings pending