martes, 18 de septiembre de 2012

Science & Research (Biologics) > Developing Gene Therapy for Cancers Using Virus Vectors

Science & Research (Biologics) > Developing Gene Therapy for Cancers Using Virus Vectors

Developing Gene Therapy for Cancers Using Virus Vectors

Food and Drug Administration (FDA) scientists successfully demonstrated in “test tube” and animal studies that it is possible to target specific cancer cells with viruses that might one day be used for gene therapy.  Gene therapy is the use of genes to treat or cure disease by using normal genes to replace a defective one or to supplement the activity of a normal one.
The FDA scientists used viruses modified to carry on their surface a certain protein that binds specifically to another protein on the surface of the cancer cell. The viruses, called lentiviruses, bound to the cancer cells and released their genetic cargo into them, both in the test tube and in tumors growing in mice. For this study, the genes were not therapeutic; rather, they control production of an enzyme called luciferase, which triggers a chemical reaction that produces bioluminescence (light) under the right conditions. The bioluminescence, captured by a special imaging device, shows where the luciferase gene is located. Using this technique, the FDA scientists showed they could deliver a gene directly to tumor cells while avoiding normal cells.
The ability of the lentivirus vector (vehicle for transferring genetic material to a cell) to deliver the luciferase gene is important because it overcomes serious obstacles to using them for gene therapy. First, it enables scientists to redirect a virus from its normal target cell so it targets the cell of interest, in this case a human glioblastoma (brain cancer) cell. In addition, the use of the modified virus vector avoided unintentional delivery of genes to other, non-target cells.
The FDA scientists, from the Center for Biologics Evaluation and Research (CBER), genetically engineered the lentivirus so it would make the H and F proteins from the measles virus and insert them onto the coating on its surface. The H protein normally helps the measles virus bind to the human cell it infects by latching onto a specific receptor on the cell.  It then signals the F protein to trigger fusion of the virus to the cell so the virus can inject its genetic material.
To create the vector, the CBER scientists further engineered the lentivirus so a protein called interleukin-13 (IL-13) was bound to the end of the H protein. The IL-13 protein allowed the virus to bind only to cells that had large numbers of the so-called receptor protein for IL-13.  While certain normal cells carry the IL-13 receptor, certain human cancer cells carry high levels (up to 50-fold higher compared to normal cells). Therefore, the modified virus attaches to the human cancer cell more efficiently than to a normal cell. The scientists showed that the lentivirus vector delivered its genetic cargo to cancer cells that were maintained in a laboratory culture. In addition, the vectors also found and attached to cells of the tumor that had been injected (xenografted) into mice, both under the skin and in the brain.
The success of the lentivirus vector as a tool for ferrying genes into the glioblastoma cells suggests that similar vectors could be developed to target additional tumors that have on their cell surface IL-13 receptor or other specific receptors.
“Specific Targeting of Human IL-13 Receptor α2-Positive Cells with Lentiviral Vectors Displaying IL-13”
Hum Gene Ther Methods
April 2012, 23(2): 137-147.
Wu Ou1, Michael P. Marino1, Akiko Suzuki1, Bharat Joshi1, Syed R. Husain1, Andrea Maisner2, Evanthia Galanis3, Raj K. Puri1, Jakob Reiser1*
1Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, MD, USA
2Institute of Virology, Philipps University of Marburg, Germany
3Mayo Clinic, Rochester, MN, USA

No hay comentarios:

Publicar un comentario