By Dr. Priyom Bose, Ph.D.Feb 16 2023Reviewed by Megan Craig, M.Sc. This newly developed technique targets multiple factors associated with GBM progression and invasiveness. The findings were published in Science Advances.
Conventional treatment of GBM includes surgery, followed by radio-and-chemo-therapy. Notably, temozolomide , a chemotherapy treatment in combination with radiotherapy has improved survival rate by two years. Mechanistically, miR-10b increases GBM growth by negatively regulating transcription factor AP-2γ , cyclin-dependent kinase inhibitor I expression, BCL2 interacting mediator of death , and tumor suppressor cyclin-dependent kinase 2A inhibitor . Similarly, GBM invasiveness is increased by up-regulated miR-21 levels.
Alternatively, knocking down miR-21 decreases GBM advancement and invasion. This treatment also reduces GBM cell’s chemoresistance to TMZ and taxol. The available GBM therapeutics mainly target a single oncomiR, which has shown reduced efficacy. Typically, PNAs bind to targeted miRNAs via a complementary DNA base pairing system, and this structure is enzymatically stable. However, compared to classical PNAs, serine-gamma PNAs , with specific modification at the γ position, exhibit superior binding affinity, physicochemical features, and specificity. Previous studies have also indicated that anti-seed sγPNAs are clinically more translatable with minimal toxicity.
In this study, PLA-HPG-CHO BNPs were loaded with two sγPNAs, one bound to miR-10b and the other to miR-21. The Gel shift assays showed the binding of the synthesized sγPNAs with the respective miR. This finding indicated that the newly designed sγPNAs were highly specific and had a strong affinity for target oncomiRs.