Gene Therapy Strategies for Retinitis Pigmentosa.
pigmentosa is the most common neurodegenerative disease that leads to blindness. The
prevalence of RP in the United States is one in 4,000 individuals, affecting
approximately 100,000 people. Worldwide, RP affects approximately 1.5 million
individuals1. Autosomal dominant RP (adRP) has been documented to account for 40-54% of
all RP cases, and although more than 80 genes ... read morehave been associated with RP, mutations in
the rhodopsin gene are responsible for nearly 50% of adRP1-5. Due to the accessibility
of the eye and genetic basis of RP, a gene therapy approach may be an attractive
treatment option. Described herein are two approaches to alleviate RP using gene
therapy. Zinc finger nucleases (ZFNs) present an opportunity to repair pathological
mutations in the rhodopsin gene in a permanent fashion by harnessing the endogenous DNA
repair process of homologous recombination following a targeted double strand break in
the rhodopsin gene. MicroRNA-mediated rhodopsin gene suppression and replacement is also
an attractive approach to treating RP, and was investigated using a novel murine model
of RP expressing a pathological human rhodopsin on a mouse rhodopsin knockout
background. This novel murine model provides advantages over previous models of RP and
was used to investigate the efficacy of the microRNA gene suppression and replacement
approach. The objective in these studies was to explore therapeutic intervention
strategies for RP6 with the ultimate goal of developing a viable treatment for this
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Genetics.
Advisor: Rajendra Kumar-Singh.
Committee: Phil Hinds, Gordon Huggins, Claire Moore, and Shalesh Kaushal.
Keyword: Genetics.read less