Gene therapy workflow

The Byrne Lab develops gene therapies for retinal disease.  Inherited retinal dystrophies include a diverse group of blinding disorders that have a profound impact on the quality of life of patients. Approximately 1 in 3000 people worldwide are affected by inherited retinal degenerations. This group of diseases involve mutations in more than 200 genes, with autosomal recessive, dominant, X-linked, and complex patterns of inheritance. Most mutations that cause retinal degeneration are expressed in photoreceptors, the light sensitive cells of the retina, or RPE cells, which provide support to photoreceptors, and these mutations result in dysfunction and eventual death of photoreceptors, leading to a loss of vision.

There are currently no effective treatments for most forms of inherited retinal degeneration. However, gene therapy, in which a healthy copy of a mutated gene or a therapeutic protein is delivered to cells in the retina, is a highly promising approach to treating retinal disease. The most effective approach to deliver a therapeutic gene to the retina is using viruses, which have evolved over millions of years as highly efficient gene delivery systems. In viral vector-mediated gene therapy, the viral genome is replaced with a cassette containing a promoter driving expression of a therapeutic transgene. The virus is then injected into the eye, where it infects retinal cells, carrying its genetic payload to the nucleus, and resulting in expression of a therapeutic protein.

Before gene therapy strategies are effective, efficient and applicable to most retinal diseases, there are significant obstacles that must be overcome. These include developing gene therapy approaches for diseases involving large genes, dominant mutations, and mutations in non-coding regions. The Byrne lab uses high throughput methods, guided by computational approaches, to engineer viral vectors with new abilities and improved capabilities to deliver therapeutic genes to the retina. We are developing new therapies that allow for increased precision of gene delivery and protein expression. Additionally, a main focus of the lab is to develop and implement gene editing approaches using CRISPR/Cas9, a powerful and widely applicable molecular tool, which we are using to directly rewrite the genome.