Gene therapy is an approach to treating disease that uses genetic information—DNA—as a drug. Monogenic diseases, where a single genetic mutation results in a nonfunctional protein and disease-causing agent, are excellent candidates for treatment by gene therapy. A virus can be engineered to carry the corrected form of the mutant gene instead of its own viral genes. These engineered viruses, called vectors, still retain their ability to infect cells, but instead of delivering harmful viral genes into the cell, they deliver the therapeutic gene, and the cell can now make the correct form of the disease-causing protein. Retinitis Pigmentosa (RP) is a disease commonly caused by  mutations in the Rhodopsin gene, and buildup of nonfunctional Rhodopsin protein leads to death of the rod photoreceptor cells of the retina, eventually leading to blindness.  Its monogenic nature makes RP  a good candidate for gene therapy. The Adeno-Associated Virus (AAV) is able to infect many cell types in the retina, and AAV is currently being used as a gene therapy vector in many clinical trials.  This beautiful image is a cross-section of a non-human primate retina that was injected with an AAV8 vector carrying DNA encoding the Green Fluorescent Protein (GFP). The layers of blue circles are photoreceptor cell nuclei, and the red and green layer below this are the photoreceptor’s outer segments where light capture occurs. The cones, which function in bright light conditions and are responsible for color vision and acuity, are stained red. The rods, which allow vision in low light conditions, are green, demonstrating that the vector has successfully delivered the GFP gene to the rod photoreceptor cells. This indicates that an AAV8 vector packaged with a therapeutic gene would likely be a successful treatment for retinal diseases such as RP.

To read more about AAV-mediated gene therapy, click here.

To watch a short video about recent advances in treating retinal disease with gene therapy, click here.

Image courtesy of Luk Vandenberghe, PhD.

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