Selective inhibition of polyglutamine protein expression
AssigneeBoard of Regents, The University of Texas System
InventorsDavid R. Corey, Jiaxin Hu, Dinah W.Y. Sah
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Abstract
The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntingtin Disease Protein and Ataxin-3 using double-stranded RNAs and nucleic acid analogs. Chemically-modified RNAs having at least one mismatch as compared to the target CAG repeat sequence are specifically contemplated.
Claims33
A method for inhibiting expression of a disease protein encoded by an mRNA having expanded CAG repeat region comprising contacting a cell that produces said disease protein with a double-stranded RNA of 15-30 bases that targets said expanded CAG repeat region of a disease protein mRNA, and said double-stranded RNA further contains 1, 2, 3, 4 or 5 base mismatches as compared to the CAG repeat, wherein (i) inhibiting is selective for said disease protein expression over expression of a normal form of said disease protein, an mRNA for said normal form which lacks said expanded CAG repeat region, (ii) and said double-stranded RNA contains no more than one base mismatch in a seed sequence.
26-27. (canceled)
A method for inhibiting expression, in a subject, of a disease protein encoded by an mRNA having expanded CAG repeat region comprising administering to said subject an amount of a double-stranded RNA of 15-30 bases that targets said expanded CAG repeat region of a disease protein mRNA, and said double-stranded RNA further contains 1, 2, 3, 4 or 5 base mismatches as compared to the CAG repeat, wherein (i) inhibiting is selective for said disease protein expression over expression of a normal form of said disease protein, an mRNA for said normal form which lacks said expanded CAG repeat region, (ii) and said double-stranded RNA contains no more than one base mismatch in a seed sequence.
32-65. (canceled)
A composition of matter comprising a double-stranded RNA of 15-30 bases that targets said expanded CAG repeat region of a disease protein mRNA, and said double-stranded RNA further contains 1, 2, 3, 4 or 0.5 base mismatches as compared to the CAG repeat, wherein said double-stranded RNA contains no more than one base mismatch in a seed sequence.
67-94. (canceled)
Dependencies are inferred from the claim text.