Gene Therapy

In both types of therapy, scientists need something to transport either the entire gene or a recombinant DNA to the cells nucleus, where the DNA is located. In essence, vectors are molecular delivery trucks. One of the first and most popular vectors developed was viral vectors, or vectors made of viruses because they invade cells as part of a natural infection process. Viruses were originally considered the most ideal vector because they have a specific relationship with the host in that they can infect specific cell types or tissues. As a result, vectors are chosen according to their affinity for certain cells and areas of the body.

One of the first viral vectors used was the retrovirus. Because these viruses are easily cloned (artificially reproduced) in the laboratory, scientists have studied them extensively and learned a great deal about their biological characteristics. They have also learned how to remove the genetic information that governs viral replication, thus reducing the chances of mutliple rounds of infection. Additionally, many of the proteins from these viruses that can cause an immune response can be removed.

Retroviruses work best in actively dividing cells, but most of the cells in the body particularly those that are fully differentiated are relatively stable and do not divide often. As a result, these cells are used primarily for ex vivo (outside the body) manipulation. First, the cells are removed from the patient's body, and the virus, or vector, carrying the gene is inserted into them. Next, the cells are placed into a nutrient culture where they grow and replicate. Once enough cells are gathered, they are returned to the body, usually by injection into the blood stream. Theoretically, as long as these cells survive, they can have therapeutic potential.

Another class of viruses, called the adenoviruses, have proven to be good gene vectors in certain cases. These cells can effectively infect nondividing cells in the body, where the desired gene product is then expressed. These viruses, which cause respiratory tract infections, are more easily purified and more stable than retroviruses, resulting in less chance of an unwanted viral infection. These viruses live for several days in the body and can have potentially life-threatening complications related to immune cell responses. Other viral vectors include influenza viruses (that causes the flu), Sindbis virus, and a herpes virus that infects nerve cells. Each of these vectors can be modified to minimize the risk of causing disease or immune cell responses.

Scientists have also developed nonviral vectors. These vectors rely on the natural biological process in which cells uptake (or gather) macromolecules (large molecules). One approach is to use liposomes, or globules of fat produced by the body and taken up by cells. Scientists are also investigating the introduction of recombinant DNA by directly injecting it into the bloodstream or placing it on microscopic beads of gold shot into the skin with a "gene-gun." Another possible vector under development is based on dendrimer molecules. This is a class of polymers or naturally occurring or artificial substances that have a high molecular weight and are formed by smaller molecules of the same or similar substances. They have been used in manufacturing Styrofoam, polyethylene cartons, and Plexiglass. In the laboratory, dendrimers have shown the ability to transport genetic material into human cells. They can also be designed with a high affinity for the membrane of a cell by attaching sugars and protein groups to it.