Exosomes targeting Myc reverse the proneural-mesenchymal transition and extend the survival of end-stage glioblastoma mice

Exosomes generated from human bone marrow Mesenchymal Stem cells (MSC) and engineered to encapsulate different anti-Myc siRNAs (iExo-Myc) and scramble-siRNAs (iExo-Scr) were administered via retro-orbital injection to mice harboring late stage intracranial U87 tumor xenografts. Tumor growth and survival were monitored, and tumor xenografts were collected and transcriptionally profiled. Next, we performed gene expression profiling analysis using data obtained from RNA-seq of U87 tumor xenografts collected at the endpoint of the survival study from 3 iExo-Myc#1 treated mice and 4 iExo-Scr#1 treated mice We implanted luciferase expressing U87 cells orthotopically in nude mice. At Day 28 post tumour implantation, mice were allocated into 2 treatment groups that received, via retro-orbital venous sinus injection, iExo-Scr #1 or iExo-Myc #1, every other day at a dose of 1x10E9 exosomes in 100 μl. When mice reached euthanisa conditions, tumors were collected and total RNA was extracted and cleaned up from iExo-Scr #1 (N=4) and iExo-Myc #1 (N=3) treated mice. RNA concentration was measured and RNA quality was assessed and an equal amount of RNA was submitted for Illumnia Next Seq 500 sequencing