Not Your Average Fairytale

By Kristen Kocher                        February 4, 2010

Numerous genetic diseases, especially hereditary brain diseases, are untreatable therefore subjecting many individuals to a life of endless pain and suffering. However, in recent years with the development of the technique of gene therapy, new hope has been brought to life in those diagnosed as “terminally ill” with the promise of the “happily ever after” ending that everyone deserves.

Gene therapy is still not used as a mainstream medical technique because much of the process is still in the developmental stages. Recently, geneticists have been desperately working to perfect the successful transport of therapy genes into brain cells. In many cases, the diseases are caused by a single gene or protein mutation but can cause devastating affects, which normally result in the loss of brain cells and fatality.

A recent scientific breakthrough has finally made it possible for therapy genes to be inserted into brain cells and cure certain genetic diseases.  Before this discovery, therapy genes were only administered through the use of viruses, predominantly the herpes virus, HSV-1. While HSV-1 has the ability to effectively transport large genes into the nucleus of the targeted cells, once the genetic information enters the nucleus it is unable to be integrated into the mammalian, host genome. This proves to be unhelpful as the therapeutic information is quickly silenced and within a few days the effects of gene therapy are no longer visible.  

Another molecule used for gene therapy transport is known as “Sleeping Beauty”. The aforementioned molecule is named as such because it is innately a silent gene that was activated, or “awakened”, by scientists. The discovery of this molecule is beneficial because it has the ability to take the target gene intended for therapy into the nucleus and integrate it directly into the mammalian genome.  The genes transported by Sleeping Beauty, however, must be relatively small, roughly 15 to 30 times less than the amount of DNA carried by HSV-1. This is unfortunate because the genes that are used for treatment of diseased brain cells are predominately large and cannot be carried by Sleeping Beauty.

So, where does the happy ending come in? These two molecules individually have characteristics that make them useful in therapy gene transport but separately cannot aid in the treatment of brain disease. However, thanks to the research of William Bowers, Ph.D. and graduate student Suresh de Silva, this blockade has been removed. With the creation of a hybrid molecule made up of both HSV-1 and Sleeping Beauty, geneticists have been able to successfully integrate large therapy genes into the mammalian genome, which, though current experiments, have resulted in long-term therapeutic gene expression. The creation of this hybrid therapy gene transport molecule promises a bright future and “happy ending” for those suffering from terminal, genetic disease.

Original Press Release

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