AAV-mediated direct in vivo CRISPR screen in glioblastoma

A direct in vivo approach for high-resolution, high-throughput mapping between specific molecular alterations and cellular phenotypes would provide an invaluable resource for understanding the mechanistic underpinnings of cancer, especially lethal cancer types such as GBM. However, a global, functional, and quantitative map of gliomagenesis in the native brain environment has been lacking due to multiple technological challenges. Here, we developed a novel technological approach – direct in vivo mapping of causative genes using adeno-associated virus (AAV) mediated CRISPR mutagenesis in fully immunocompetent mice, which we utilized to perform high-throughput mutant analysis of glioblastoma suppressors.