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> John Flannery
Reseach Interests
The therapeutic potential of gene transfer as a treatment for retinal
disease is promising, yet substantial technical and theoretical
problems remain to be solved before clinical application. To date,
numerous gene therapies for retinal disease have been proposed,
these fall into two main categories: gene augmentation for dominant
disease and gene replacement for recessive null mutations.
In gene replacement, a normal copy of a defective gene is introduced.
Dominant disease has been treated by inhibiting apoptotic cell death
with neurotrophins, and 'knockdown' strategies to reduce the mutant
gene product using ribozymes and anti-sense RNAs. These approaches
have achieved success in animal models.
Our ultimate goal is to discover gene delivery systems that when
introduced into the eye will delay or prevent the degeneration of
photoreceptors in patients with retinal dystrophies.
About one person in 2,000 has an inherited retinal dystrophy. Currently,
there is no effective treatment for any retinal degeneration. The
vast majority of patients retain good retinal function for a period
of years; however, vision progressively worsens due to apoptotic
photoreceptor cell death. We use viral vectors derived from AAV,
a non-pathogenic human virus, and FIV, the feline immunodeficiency
virus to transfer therapeutic genes to photoreceptors.
These vectors take advantage of the natural efficiency with which
viruses deliver genes to cells. We evaluate the therapeutic effect
of gene transfer in several transgenic rodent models of retinal
degeneration, with the idea that the tools and strategies developed
and tested will be relevant to human retinal degenerations.
It is clear to us that if we can block photoreceptor cell death
for any significant time in an animal model, that this will hold
promise for use in humans and, ultimately, for a clinical trial
in patients.
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