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Protein Transduction Update. |
A recent issue of Science reported significant developments in protein transduction. The report demonstrated that proteins injected into the abdomen of a mouse could be rapidly transported to all cell types tested including the brain. Typically, intact proteins are unable to pass through cell membranes. This breakthrough technology has tremendous potential in the treatment of disease as well as in basic scientific research.
Currently a novel treatment for AIDS(HIV) is being developed that employs this technique. It uses the HIV protease to activate a protein which tells the infected cell to commit suicide thus preventing HIV replication. This treatment should not impact uninfected cells. The use of protein transduction as an AIDS therapy is ironic because the protein transduction domain (PTD) is derived from HIV, the virus that causes AIDS. Cancer is another disease that may be treated through protein transduction. It may also be employed with hereditary diseases caused by the lack of a protein such as Tay-Sachs disease.
The ability of the PTD to carry proteins into cells was first reported ten years ago. Five years ago, this transport activity of the PTD was shown to be a short segment that may tag any protein and enable it to enter cells. Initially the efficiency of the PTD tag to carry proteins into cells was very low. Dr. Stephen Dowdy's laboratory determined that inactivating proteins enabled much more efficient transportation into cells. They found that they could rely on the cellular machinery to refold the protein into its active form. This technique has been applied to over 50 different proteins of various sizes. Each of these proteins regains normal activity once carried into a cell by the PTD.
No side effects have been observed in animals that have been repeatedly subjected to protein transduction. However, the powerful ability of the PTD to transduce proteins also makes it potentially hazardous. If an accident happened and a PTD labelled protein was inhaled or ingested it would spread throughout the body. Therefore great care will need to be taken when attaching this tag to potentially toxic proteins.
This report shows that a single injection of proteins tagged with PTD is sufficient for the protein to be found in an active form in every cell type tested. The proteins pass through the blood-brain barrier and are detectable in the brain within four hours of injection. This innovation opens up enormous possibilities in practical protein therapies. Protein transduction based approaches circumvent many of the obstacles associated with gene therapy. It is not difficult to envision treatments for cancer, other infectious diseases, genetic diseases and the degenerative diseases of aging arising from this new technique.In addition protein transduction will yield broad potential applications to basic research such as characterizing the proteins discovered during the Human Genome project.
Created October 3rd, 1999. Copyright 1999 by Duane Hewitt
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