Gene therapy approaches using reproducible and fully penetrant lentivirus-mediated endogenous glioma models

Abstract

Animal models have proven invaluable for progress toward greater understanding of the etiology, pathogenesis, and genetics of a wide range of human diseases. The development of relevant brain tumor animal models is a critical resource for building our understanding of cancers that arise within the brain and for the development of novel therapies. The central role of these models is particularly apparent for gliomas, which are common and devastating primary brain tumors. Effective models accurately demonstrate pathological features and behavior that are analogous to the human disease. Models aim to develop tumors with high penetrance and low latency, features that are ideal for preclinical therapeutic development. Lentiviral vector-induced models fulfi ll these requirements while giving investigators excellent control over the genetic profi le of resulting tumors. This fl exibility is especially relevant in the context of recent advances in the understanding of the genetic lesions found in human grade IV glioma, glioblastoma multiforme (GBM). Further, these endogenous tumor models would be ideal for the testing of novel gene therapy strategies which could potentially be implemented in Phase 1 clinical trials for these devastating human brain cancers.