TITLE: Oligonucleotide Modulation of Splicing
INVENTORS: David Corey
TECHNOLOGY: Biologicals
UTSD: 2402
SUMMARY: Newly synthesized transcripts (pre-mRNAs) contain intervening sequences
(introns). These introns must be excised from the pre-mRNA by the spliceosome, a
ribonucleoprotein complex. The remaining portions of the pre-mRNA (exons) are then spliced
to form the mature mRNA that codes for proteins. Splicing occurs in the nucleus and spliced
transcripts are exported into the cytoplasm. Splicing usually does not produce a single mRNA
species for each gene. Instead, pre-mRNAs are spliced in alternate ways, leading to production
of different proteins. This phenomenon is known as alternative splicing and is observed in over
90% of all human genes. Approximately 60% of disease-causing point mutations are related to
defective splicing and chemical agents that redirect splicing may promote production of protein
isoforms to compensate for genetic defects. The invention provides a method for modulating
splicing of a pre-mRNA comprising contacting a cell that produces a pre-mRNA with alternative
splicing with a double-stranded RNA of 15-30 bases that targets a splice junction or exonic or
intronic sequences adjacent thereto, wherein the double-stranded RNA contains one or more
centrally located mismatches. The pre-mRNA may encode a protein that is aberrantly spliced
in a disease state, such as the Duchenne muscular dystrophy protein or survival motor neuron
2. The present invention relates to the selective modulation of pre-mRNA splicing, in particular,
for that involving alternative splicing in disease-related proteins such as those involved in
Duschenne’s Muscular Dystropy and Spinal Muscular Atrophy.
Please contact the Office for Technology Development for more details:
Phone: 214-648-1816
Email: TechnologyDevelopment@utsouthwestern.edu
Please reference UT Southwestern Case Number: 2402