TITLE: CUG Repeat RNA Nuclear Foci: A Novel Therapeutic Target for Treatment of Fuchs'
Endothelial Corneal Dystrophy
INVENTORS: Mootha
TECHNOLOGY: Biologicals
UTSD: 2903
SUMMARY: Fuch’s endothelial corneal dystrophy (FECD) is an autosomal dominant agerelated degenerative disorder resulting in corneal edema and loss of vision. This bilateral,
progressive disorder occurs in 5% of Caucasians over 40 in the U.S.
As previously published, expansions of the the intronic CTG18.1 repeat locus within TCF4 are a
common casual variant for FECD in Eurasion populations. This invention is the discovery of
discreet nuclear RNA foci containing expanded CUG transcripts in cells from FECD subjects
with CTG18.1 expansion is disclosed. Data from the inventors indicates that the presence of
nuclear RNA foci are not a non-specific marker for corneal endothelium dysfunction but a finding
for CTG18.1 expansion-mediated endothelial disease.
Antisense technology can be employed to prevent/disrupt CUG RNA inclusions by targeting the
mutant transcript and preventing it’s interaction with host cell proteins. Direct administration of
nucleotides including but not limited to morpholino oligonucleotides and 2’-O-methylphosphorothioate-modified (CAG) 7 AON (antisense oligonucleotides) that target poly CUG
repeat tract in the intron of the gene encoding TCF4. The use of engineered U7 small nuclear
RNAs containing a poly-CAG antisense sequence could also be used. Furthermore, the use of
small moleculaes that partially target CUG repeats/hairpin structures to release sequestered
RNA binding proteins may result in the prevention/destruction of nuclear foci.
Please contact the Office for Technology Development for more details:
Phone: 214-648-1888
Email: TechnologyDevelopment@utsouthwestern.edu
Please reference UT Southwestern Case Number: 2903