Development of gene therapies for recessively inherited RP2- and TULP1-linked retinopathies

Lead Researcher:

Prof Jane Farrar

Award Date:

1 January 2013

Host Institution:

Trinity College Dublin

Scheme:

Health Research Award

Summary:

The altered (mutant) genes causative of many inherited disorders have been identified over the past two decades. In addition methods of delivering genes to target tissues have also been established; frequently, modified viruses are utilised to achieve gene delivery as their ability to readily infect cells is exploited. It has been shown that such viruses, and in particular a virus termed adeno associated virus (AAV), is well tolerated when injected under the retina (subretinally) in the human eye providing an opportunity to use AAV to deliver wild type (healthy) genes to compensate for the mutant genes present in some inherited eye disorders. This is the strategy adopted in the current study for two severe inherited eye disorders which cause a devastating loss of vision termed RP2- and TULP1-linked retinal degenerations. Patients with these disorders have two copies of the mutant genes and so have no normal (wild type) copy - they are said to be suffering from recessively inherited retinal degenerations. In principle, supplying a wild type copy of the gene should provide the wild type (normal) encoded protein that is missing and thereby provide therapeutic benefit –the basis of all replacement gene therapies. In the current study mice with RP2- and TULP1-based retinal degenerations, similar to the human diseases, will be treated with AAV viruses that are engineered to contain either the RP2 or TULP1 genes. A single subretinal injection of virus will be undertaken per mouse eye. The effects of the gene replacement therapies will be evaluated by looking at the structure of retina and by evaluating the responses of the mouse eye to light in treated eyes. The study provides a real opportunity to develop novel and powerful gene therapies for these two debilitating eye conditions.