Title : Development of novel miR-dependent genome-editing Adeno-associated virus that selectively eradicates glioblastoma-initiating cells
Abstract:
Glioblastoma (GBM), one of the most malignant human cancers, frequently recurs despite multimodal treatment with surgery and chemo/radiotherapies. One of the reasons of why GBM recues is likely the existence of GBM-initiating cells (GICs) that have strong proliferative and tumorigenic abilities and are resistant to various types of chemotherapies and radiotherapy. It is therefore crucial to find novel methods that specifically kill GICs by targeting their characteristics. Previously, we have identified various factors, such as membrane proteins, transcription factors and microRNA (miR), which increase or decrease in GICs compared with normal neural stem cells (NSC), and demonstrated their functions in GICs. On the process developing novel methods for GBM therapy, we noticed that these factors are considerably expressed in the cells of non-central nervous system, suggesting the concerned side effects if we target these factors for therapy. To overcome this hurdle, we combined our previous findings with the genome-editing system and developed new miR-dependent genome-editing Adeno-associated virus (AAV) that selectively killed GICs reducing off-target effects to normal cells. I will present the anti-tumorigenic ability of our new AAV in my talk.
Audience Take Away Notes:
- The audience leans that a combination of two GIC-related factors can specifically target GICs but not normal resident cells.
- The audience learns how our miR-dependent genome editing system can selectively eliminate GICs with reducing side-effects and can apply our method for their research.
- I also provide a method how to deliver genes into the transplanted human cells using systemically delivered AAV.