Mechanics
How does gene therapy work?
A normal gene is inserted into the genome to replace an abnormal (disease-causing) gene. A carrier molecule called a vector is used to deliver the therapeutic gene to the patient's target cells. The most common vector used is a virus that has been genetically altered to carry normal human DNA.
Target cells (-for mesothelioma, mesothelial cells-) are infected with the viral vector. The vector unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state.
There are several nonviral gene-delivery systems as well. Direct introduction of therapeutic DNA into target cells is the simplest method. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA.
In another nonviral approach, an artificial lipid sphere with an aqueous core called a liposome is created in the lab. . The spheres, which are basically fat bubbles, are created around plasmids, which are small, circular pieces of DNA. Once injected into the body, the liposomes can fuse with cell membranes, emptying their plasmid DNA contents into the cells.
Therapeutic DNA also can get inside target cells by chemically linking the DNA to a molecule that will bind to special cell receptors. Once bound to these receptors, the therapeutic DNA constructs are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options.
Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell.
Anna L. Kaplan, M.D.
