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

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. Overall design: Next, we performed gene expression profiling analysis using data obtained from single nuclei RNA-seq of U87 tumor xenografts collected at the endpoint of the survival study from 2 iExo-Myc#1 treated mice and 2 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