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How Does Gene Therapy Work?

Gene therapy can be used to introduce new genetic material into cells to compensate
for an abnormal gene. For example, if a mutated gene causes an important protein to be faulty or missing, gene therapy may be used to introduce a normal copy of the gene. The protein expressed from the newly introduced gene would restore the normal function of the protein.

A gene that is targeted for delivery to a cell usually needs to efficiently make contact with the cell, penetrate the cell membrane, reach the nucleus of the cell, penetrate the nuclear membrane, and be delivered to the DNA within the chromatin of the nucleus of the cell. A "vector" is a natural or manufactured construct of genetic material that carries the gene into the cell.

Certain viruses are often used as vectors because they have a natural ability to recognize certain cells and insert genetic material when they infect the human body. However, the viruses are first modified so they can’t cause disease in people. Some types of virus, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. Other viruses, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses used as vectors include adeno-associated viruses, lentiviruses, poxviruses, and herpes viruses.

In a form of gene therapy called "in vivo gene therapy," the vector which is often a virus or a liposome (a fatty particle) can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells.

Another form of gene therapy is called "ex vivo gene therapy," because the gene is transferred into the patient’s cells while the cells are outside the patient’s body. This is done by removing cells from the patient’s blood or bone marrow and growing the cells in the laboratory. The cells are then exposed to a virus carrying the desired gene. The virus enters the cells and inserts the desired gene into the targeted cells' DNA. The cells are grown in the laboratory and are then returned to the patient by injection into a vein.

When using either in vivo or ex vivo gene therapy, the treatment is considered successful
when the new gene delivered by the vector is expressed in the targeted cells and makes a functioning protein.

How is Gene Therapy Being Studied in the Treatment of Cancer?

Researchers are studying several ways to treat cancer using gene therapy. Some approaches target healthy cells to enhance their ability to fight cancer. Other approaches target cancer cells, to destroy them or prevent their growth. Some gene therapy techniques under study are described below:

  • In one approach, researchers replace missing or altered genes with healthy genes. For example in some human families, a gene mutation may occur in a gene that encoded a key regulatory protein called "p53." The p53 protein acts as a checkpoint that prevents uncontrolled cell proliferation. Gene therapy is used to substituting the mutated p53 protein restoring the body with “working” copies of the p53 gene.
  • Researchers are also studying ways to improve a patient’s immune response to cancer. In this approach, gene therapy is used to stimulate the body’s natural ability to attack cancer cells. In one method under investigation, researchers introduce the gene encoding a functional T-cell receptor (TCR) ex vivo into the cells of the T-lymphocytes obtained from a patient. When these white blood cells are transferred back into the patient, they stimulate the body to recognizing certain molecules found on the surface of the tumor cells and activating the body to kill the tumor cells.
  • In other cases, scientists are investigating the insertion of genes into cancer cells to make them more sensitive to chemotherapy, radiation therapy, or other treatments. Alternatively, gene can be introduced into health cells that that makes them more resistant to the side effects of high doses of anticancer drugs.
  • In another approach, researchers introduce “suicide genes” into a patient’s cancer cells.
  • Other research is focused on the use of gene therapy to prevent cancer cells from developing the new blood vessels that supply them with nourishment ("angiogenesis").

Multimodality therapy for mesothelioma