"The study required a combination of genetic tools and surgical technique to make sure the therapy targeted only the diseased cells. The viral vector had to be injected in the sub-retinal space so as to be in close proximity to the photoreceptors. Likewise, you need to ultimately deliver the therapy to the right location of the retina," Aguirre said.
"In the human disease, careful characterization of the areas of the retina that need to be treated is going to be critical for therapy to succeed in the clinic," Cideciyan said.
The genetic aspect of the viral vector used in this study involved a double safeguard. The first safety feature was to use a viral vector that is known to predominantly target both rods and cones but not other cells. The second safeguard involved attaching the healthy RPGR gene to a "promoter," a piece of genetic code that would "switch on" the gene only if the virus penetrated the correct cell.
Selecting the right promoter was critical; the lead researchers at the University of Florida, William W. Hauswirth and Alfred S. Lewin, had to find one that that would be turned on exclusively in rods and cones. This way, even if the virus made its way to a non-photoreceptor cell, that cell would not start activating the RPGR gene.
That both the promoter and the RPGR gene it activates are taken from humans is a strong sign that the treatment may be translatable to patients.
"While there is still much work to do to assess long-term efficiency and safety with this approach, there is hope that this vector and knowledge could be used in a few years to treat the many patients losing vision from XLRP," Jacobson said.
|Contact: Evan Lerner|
University of Pennsylvania