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AssigneeMedical Diagnostic Laboratories, LLC
InventorsGrant Gallagher, Raymond Yu, Jonathan Brazaitis
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The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rα gene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.
An anti-sense RNA oligonucleotide 15-30 nucleobases in length targeted against exon 9 of IL-23Rα gene that increases the production of a soluble truncated IL-23Rα protein having an amino acid sequence set forth in SEQ ID NO:
A method of producing a soluble truncated IL-23Rα protein comprising the step of exposing an anti-sense RNA oligonucleotide to a mammalian cell, wherein said anti-sense RNA oligonucleotide is targeted against exon 9 of IL23Rα gene to induce skipping of exon 9 in said cell, and is selected from the group consisting of SEQ ID NO:
A method of treating a human subject inflicted with Crohn's disease, comprising the step of administering a therapeutically effective amount of an anti-sense RNA oligonucleotide to said human, said anti-sense RNA oligonucleotide is targeted against exon 9 of IL-23Rα gene, and induces the production of a soluble truncated IL-23Rα protein having an amino acid sequence set forth in SEQ ID NO:
Dependencies are inferred from the claim text.