Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery

Journal of Neuro-oncology
Adrienn VolakCasey A Maguire

Abstract

The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promot...Continue Reading

References

Aug 1, 1991·The Journal of Clinical Investigation·M A BrachD Kufe
Apr 29, 2005·Journal of Virology·Guido WollmannAnthony N van den Pol
Apr 4, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Thomas C HardingKarin Jooss
Mar 16, 2007·Clinical Oncology : a Journal of the Royal College of Radiologists·R O EscárcegaA Zamora
Aug 21, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Casey A MaguireMiguel Sena-Esteves
Dec 23, 2008·Nature Biotechnology·Kevin D FoustBrian K Kaspar
Jan 13, 2009·The Journal of Infectious Diseases·Roberto CalcedoJames M Wilson
Jun 25, 2010·Journal of Leukocyte Biology·Subhra K Biswas, Claire E Lewis
Jan 21, 2011·BMC Neuroscience·Jisook LeeBrian P Eliceiri
Aug 4, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Adam K BevanBrian K Kaspar
Feb 9, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Casey A MaguireJohan Skog
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Jan 26, 2013·PloS One·Barbara H RathPhilip J Tofilon
May 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ping MaoIchiro Nakano
Jul 3, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Seemin Seher AhmedGuangping Gao
Jan 5, 2014·Chinese Journal of Cancer·Andreas F HottingerKrisztian Homicsko
Feb 15, 2014·Molecular Cancer Therapeutics·Caroline HappoldMichael Weller
Apr 12, 2014·Acta Neuropathologica·Rainer Glass, Michael Synowitz
Jun 17, 2016·Molecular Therapy. Methods & Clinical Development·Awilda M RosarioParamita Chakrabarty
Dec 10, 2016·Molecular Therapy. Methods & Clinical Development·Jonathan DashkoffEloise Hudry
Jan 14, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bence GyörgyCasey A Maguire
Aug 12, 2017·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Bence György, Casey A Maguire

❮ Previous
Next ❯

Citations

Mar 1, 2019·British Journal of Pharmacology·Lars M IttnerYazi D Ke
Aug 5, 2020·Cell Communication and Signaling : CCS·Amir B GhaemmaghamiMichael R Hamblin
Feb 8, 2020·Cellular and Molecular Bioengineering·Zhenjiang ZhangMichael R King
Aug 28, 2020·Frontiers in Molecular Neuroscience·Roberta AndrejewHenning Ulrich
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Christos DogrammatzisMaria Kalamvoki
Jan 28, 2021·Cancer Cell International·Xin XuXiaochun Zhang
May 4, 2020·International Journal of Biological Macromolecules·Zhao-Yu ShiXiu-Li Guo
Sep 7, 2021·Frontiers in Cell and Developmental Biology·Bin LiuYaxuan Liang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

AAV-based Gene Therapy

Adeno-associated virus (AAV)-based gene therapy is a biological vector that is being researched to be used as a potential therapeutic option. This gene therapy is designed to insert fragments of DNA into targeted cells to help treat diseases, such as hemophilia a. Discover the latest research on AAV-based gene therapy here.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.