Tuesday, 3 April 2012

Viruses curing blindness?

Viruses are known to insert their DNA into other cells in order to produce more of them. However, first used in the 1970’s, viral vectors are modified viruses that can insert specific DNA chosen by the scientists who form the culture.

This idea has been developed and has been taken to clinical trials by the University of Oxford, forming a modified adeno-associated virus designed to insert a gene into human eyes. The virus will replace another inheritable gene that causes an advancing form of blindness called choroideremia. Blindness from the disease usually takes hold at the age of 45 and there are around 50,000-100,000 people affected by it.
Figure 1 Dr. Maclaren from the University of Oxford, talking to Jonathan Wyatt, the first patient to be treated by the gene therapy.

Viral vectors essentially follow the same transduction pathway as normal viruses do although many are modified so that virus does not become pathogenic. The types of genes that are changed include those that manage replication and those that cause the cell to denature or change its biological process. However they are replaced with the genetic material that is designed to be inserted into the cell’s genome.

Adeno-associated virus (AAV) in the form of a drug named rAAV2.REP1 is used in this gene therapy clinical trial since it is a virus that has not been observed to cause disease. Therefore it does not create a large immune response and can be used to transduce many types of retinal cells.

Figure 2 Crystal structure of adeno-associated virus (AAV)

This specific viral vector is aimed at light-sensitive photoreceptor cells of the retina. Choroideremia takes place here but is caused by mutations in the CHM gene which is found on the X chromosome. The condition is an X-linked recessive pattern meaning that males are much more susceptible to it. However unlike other types of degenerative retinal diseases causing blindness, the gene causing this disease has been clearly identified.