Emory
Researcher Receives Emory/Georgia Institute of Technology Grant Funding
to Study Retinal Gene Defects
Jeffrey H.
Boatright, PhD, assistant professor, Emory Eye Center, has been awarded
an Emory/Georgia Institute of Technology Seed Grant for one year in
the amount of $40,000. His collaborator at Georgia Tech is Roger Wartell,
PhD, chairman of the School of Biology.
The purpose of the grant
is to develop a novel strategy for repairing gene defects that underlie
retinal degenerations in mouse models of retinitis pigmentosa (RP).
"Dr. Wartell and I are exploring
a gene therapy strategy in which the naturally-occurring DNA repair
capabilities of an affected individual are recruited to convert a mutation
in the individual's genome to wild type," says Boatright. "We have chosen
an animal model of a human form of a genetic disease that can cause
blindness (retinitis pigmentosa). We hope that an approach optimized
in the mouse model can be transferred to the human condition in order
to prevent or ameliorate disease," he concludes.
"The only way we will be
able to achieve progress in genetic modification is through collaboration
with faculty in institutions that bring to the table disparate specialties—such
as that between Emory's medical sector and Georgia Tech's engineering
expertise," says Thomas M. Aaberg, Sr., director of the Emory Eye Center
and chairman of the Emory School of Medicine Department of Ophthalmology.
"This very exciting work between two gifted investigators will undoubtedly
foster innovative research."
BACKGROUND
Most current forms of gene
therapy either add synthetic copies of genes back to the affected individual
(to make up for the gene product [protein or messenger RNA] insufficiency
caused by the gene mutation) or the therapies are designed to destroy
gene product (to prevent diseases caused by a deadly protein that results
from the gene mutation). The goal of Boatright's and Wartell's strategy
is to actually repair the mutation in the endogenous gene DNA sequence
so that the individual makes the correct gene product, in the correct
tissue, at the correct time, and in the correct amount.
In this strategy, a short
piece of chemically-modified, single-stranded therapeutic DNA is introduced
into the affected individual or into affected cells. The therapeutic
DNA targets the region of the genome that contains the mutation. The
binding of the therapeutic DNA to the targeted gene recruits endogenous
repair mechanisms that change the mutation to the correct, wild type.
Their pilot studies indicate
that the mouse and human retina contain DNA repair enzymes shown to
be requisite for this strategy. Additionally, in vitro tests show that
therapeutic DNA constructs can indeed recruit repair activity from protein
extracts of mouse and human retina. Finally, tests with human and mouse
cells and with mice in vivo show that endogenous gene repair occurs
in the eye following treatment with several different therapeutic DNA
fragments.
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