Viruses in Gene Therapy

Since the publication of the human genome in 2003 great developments have been made in genetic technology. But one of the big challenges is developing reliable methods for the delivery of the desired gene to cells in a human body. This is where our old enemy the virus can help us, as I mentioned briefly in my post about targetting therapies.

Viruses are the smallest form of life, essentially just parasitic packets of genetic material. They have adapted to infect a a variety of tissues, using a variety of different methods to get their various forms of genetic material into the cell. All this variation makes viruses more diverse than all the other forms of life put together, as viruses have adapted to use them all and for each species there are a whole collection of associated viruses. This variation also provides us with a potential toolbox which we can use to achieve our own objectives.

Having small and well understood genomes, viruses are easily modified to carry genes of human interest, and there you immediately have a highly efficient gene delivery mechanism. This method has produced an interesting range of viral therapies for a range of diseases. One company that is pursuing this technology in a broad range of diseases is Oxford Biomedica, which has a range of viral based gene therapies for diseases including Parkinson's disease, age-related and diabetic sight-loss, and in early development; motorneurone disease, AIDS, spinal cord injury; haemophilia. These developing therapies all utilise a modified horse Lentivirus to deliver therapeutic genes to a specific tissue.

Parkinson's disease involves a depletion in the brain of the critical neurotransmitter dopamine which adversely affects the brains normal functioning. Oxford Biomedica's viral therapy carries three genes into the brain tissue, which encode enzymes that produce dopamine. This new dopamine production increases the level to a point where normal brain function can resume, as shown in animal models and currently looking very promising in early human trials. The sight-loss therapy works in a similar way; The virus is modified to target only the desired retinal cells and delivers genes that halt the uncontrolled growth of blood vessels on the retina that occurs in certain eye diseases.

Hereditary conditions have been successfully treated, as shown by experiments by University of Pennsylvania Medical School and University College London with a rare form of hereditary blindness called Leber congenital amaurosis. In this therapy they inject into the eye a tamed strain of Adenovirus carrying a working copy of the mutated gene that causes the blindness. Vision improved enough for the patients to sucessfully navigate an obstacle course in dim light, a task that would previously have proved very difficult for them. There are six genes involved in the disease so further improvements may be made to the treatment by including more of these genes. The teams also believe the treatment may cause more improvement in children, as their retinas will have degenerated less than adults.

As the understanding of genetic causes of diseases, both acquired and hereditary, are being developed faster than ever by geneticists, the opportunities for gene therapies such as those described become ever more numerous. Viruses are going to be instrumental in delivering these therapies to the cells that need them.