Gene Therapy Approaches Using Reproducible and Fully Penetrant Lentivirus-Mediated Endogenous Glioma Models

  • John Lynes
  • Carl Koschmann
  • Mia Wibowo
  • Vandana Saxena
  • Marianela Candolfi
  • Mariela A. Moreno Ayala
  • Maria G. CastroEmail author
  • Pedro R. Lowenstein
Part of the Neuromethods book series (NM, volume 98)


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 fulfill these requirements while giving investigators excellent control over the genetic profile of resulting tumors. This flexibility 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.

Key words

Animal model Lentivirus Glioma Glioblastoma Gene therapy p53 PDGF AKT HRAS 



This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) Grants 1UO1-NS052465, UO1-NS052465-S1, 1R21-NSO54143, 1RO1-NS057711, 1RO1-NS074387, MICHR Pilot R14 U040007, and BioInterfaces Institute, University of Michigan U042841 to M.G.C.; NIH/NINDS Grants 1RO1-NS054193, 1RO1-NS061107, 1RO1-NS082311, R21-NS084275, and M-Cube U036756 University of Michigan to P.R.L.; the Department of Neurosurgery, University of Michigan School of Medicine; the Michigan Institute for Clinical and Health Research, NIH UL1-TR000433; University of Michigan Cancer Biology Training Grant, NIH/NCI (National Cancer Institute) T32-CA009676; University of Michigan Training in Clinical and Basic Neuroscience, NIH/NINDS T32-NS007222; and the University of Michigan Medical Scientist Training Program, NIH/NIGMS (National Institute of General Medicine Sciences) T32-GM007863, and the National Institutes of Health through the University of Michigan’s Cancer Center Support Grant P30-CA046592. C.K. is supported by an NIH T32 training grant under Dr. James Ferrara (2-T32-HL-007622-26-A1). M.C. receives financial support from the National Council for Science and Technology (PIP 114-201101-00353, CONICET, Argentina). M.A.M.A. is supported by a doctoral fellowship from CONICET (Argentina). We are grateful to Dr. Karin Murasko for her academic leadership and D. Tomford and S. Napolitan for their superb administrative support.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • John Lynes
    • 1
    • 3
  • Carl Koschmann
    • 2
  • Mia Wibowo
    • 1
    • 3
  • Vandana Saxena
    • 1
    • 3
  • Marianela Candolfi
    • 4
  • Mariela A. Moreno Ayala
    • 4
  • Maria G. Castro
    • 1
    • 3
    Email author
  • Pedro R. Lowenstein
    • 1
    • 3
  1. 1.Department of Neurosurgery, School of MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Department of Pediatric Hematology/OncologyUniversity of MichiganAnn ArborUSA
  3. 3.Department of Cell and Developmental Biology, School of MedicineUniversity of MichiganAnn ArborUSA
  4. 4.Instituto de Investigaciones Biomedicas (INBIOMED), National Council for Science and Technology (CONICET)University of Buenos Aires School of MedicineBuenos AiresArgentina

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