by Jake Meyer
A December 29th, 2009 article in The New York Times describes a new technique that allows for the editing of human genes. The technique uses natural agents called "zinc fingers," two loops of protein that can recognize specific sequences of DNA have multiple potential uses. Zinc fingers could be used in the future to engineer new crop plants, treat human diseases, and to make alterations to sperm or egg cells –- alterations that would be inheritable.
Zinc fingers can be used to turn on or off a gene at a specific DNA site. An agent that turns the gene on or off can be linked to the zinc finger, which recognized and attaches to the specific DNA site. But zinc fingers have another use which makes them a promising technology for gene therapy –- they can cut out and insert DNA from the gene sequence.
To cut out DNA, two sets of zinc fingers are attached at two different sites and a protein attached to the zinc fingers removes the DNA between the two sites. The cell containing the DNA, quickly repairs the DNA where the cut was made, but the method can be used to disrupt the gene. Dr. Carl June and his colleagues at the University of Pennsylvania are using this technique to destroy the gene for the receptor that the AIDS virus uses to gain entry to white blood cells. A clinical trial is currently being conducted to determine if patient's T cells that with the gene disrupted can be infused back into the body to reconstitute a patient’s immune system and overcome the AIDS virus.
DNA can also be inserted into a gene using zinc fingers. If DNA is inserted in a cell when zinc fingers are used to cut out DNA from two sites, when the cell repair the break in the DNA, the new DNA will be incorporated. This technique could solve previous difficulties with gene therapy that made it impractical and sometimes dangerous. Previous attempts in gene therapy to insert DNA had used modified viruses to carry the new DNA, but the techniques using a virus cannot direct the virus to a specific site. And a 1999 gene therapy experiment at the University of Pennsylvania using a modified virus resulted in the death of Jesse Gelsinger.
Zinc fingers could be the answer to a lot of problems in the gene therapy field. New gene therapy techniques could be developed allowing for many human diseases to be cured, by for instance removing DNA associated with a disease and replacing it with normal functioning DNA. However, patents on gene sequences could impede the development of gene therapies using zinc finger technologies.
Over 20 percent of the human genome is patented, and many of these patents are on genes associated with disease –- i.e. breast cancer, cystic fibrosis, Long QT. The development of gene therapies using zinc fingers to insert DNA would require researchers to acquire licenses to the gene to be used in the therapy from the gene patent holders. A gene patent holder has a monopoly over the gene and could refuse to grant a license, halting the progress of the research. And if the researcher does continue without a license, the holder of the gene patent can prevent the researcher from marketing it or can demand a huge royalty. Further, acquiring licenses for the technologies required may be prohibitively expensive. A researcher investigating gene therapies using zinc finger technologies to cure a particular disease, would have to acquire licenses to the genes associated with the particular disease as well as the cost of acquiring zinc finger technology. But the cost of making zinc fingers (200 steps) or buying zinc fingers (Sigma-Aldrich charges $39,000) coupled with the cost of acquiring licenses to research a particular gene could deter a researcher, slowing the development of a technology with great possibility of producing cures.