Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun;132(12):1100-1109.
doi: 10.1038/s41416-025-03007-3. Epub 2025 Apr 12.

Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system

Zhe Wang  1 , Peilin Zou  1 , Zhenzhong Chen  1 , Jiahui Hou  1 , You Lee Son  1 , Daisuke Yamashita  2 , Toru Kondo  3
Affiliations

Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system

Zhe Wang et al. Br J Cancer. 2025 Jun.

Abstract

Background: Since glioblastoma (GBM)-initiating cells (GICs) were identified as the cells-of-origin for GBM, various GIC factors have been analyzed as potential therapeutic targets. However, these targets are also present in normal cells outside of the brain, raising concerns about potential side effects when directly targeted. The aim of this study is to develop a novel method that specifically eradicates GICs with reducing side effects.

Methods: We selected micoRNAs (miRs) that are significantly decreased in GICs compared to normal cells and developed a genome-editing (GE) system that knocks out a functional GIC factor in a miR-dependent manner (miR-dependent GE). Additionally, we developed mosaic-capsids that consist of braintropic and universal capsids, which deliver genes into GIC brain tumors.

Results: Systemic administration of the mosaic-capsids Adeno-associated virus (AAV) carrying a miR-dependent GFP expression cassette selectively expressed GFP in GICs transplanted into the brains of immunodeficient mice, without expression in either mouse brain cells or non-brain tissues. The mosaic-capsids AAV carrying a miR-dependent GE prevented GIC tumorigenesis in the brain and extended the survival time of tumor-bearing mice.

Conclusion: These data indicate that the mosaic-capsids AAV containing a miR-dependent GE represents a novel therapeutic virus for GBM with fewer side effects.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Five primary human glioma samples, including three GBMs, one anaplastic astrocytoma (AA), and one diffuse oligodendroglioma (DO), were collected from Ehime University Hospital. Informed consent was obtained from all patients according to the Research Ethics Committee guidelines (approval number: 1208009) and the specimens were used to prepare glioma lines, GICs (E3, E6, E16), AA, and DO. The glioma lines were used in compliance with the research guidelines of the Ehime University Graduate School of Medicine and the Institute for Genetic Medicine of Hokkaido University.

References

    1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. - PubMed
    1. Singh SK, Clarke ID, Hide T, Dirks PB. Cancer stem cells in nervous system tumors. Oncogene. 2004;23:7267–73. - PubMed
    1. Kondo T. Brain cancer stem-like cells. Eur J Cancer. 2006;42:1237–42. - PubMed
    1. Vescovi AL, Galli R, Reynolds BA. Brain tumour stem cells. Nat Rev Cancer. 2006;6:425–36. - PubMed
    1. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8. - PubMed

LinkOut - more resources