Oligonucleotides for treating expanded repeat diseases
AssigneeSarepta Therapeutics, Inc.
InventorsPeter Linsley, Brian James Leppert, Gunnar J. Hanson
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Abstract
The invention provides for a method for selectively reducing the expression of a mutant mRNA and/or protein having an expanded nucleotide repeat relative to a wild-type mRNA, comprising contacting a cell with an antisense oligonucleotide of sufficient length and complementarity to the expanded nucleotide repeat. More particularly it relates to selectively reducing the expression of mutant Huntington protein associated with Huntington's disease. The antisense oligonucleotide comprising either a nucleotide or a repeated three nucleotide sequence as defined in the claims.
Claims26
An antisense oligonucleotide of 10-40 nucleotides in length having a sequence complementary to an expanded DNA repeat which is associated with a human disease, wherein the antisense comprises a nucleotide having a formula:
- wherein Nu is a nucleobase;
- R1 is —N(Me)2
- Rx is selected from the group consisting of HO—, a nucleotide, and piperazinyl;
- Ry is selected from the group consisting of hydrogen, a C1-C6 alkyl, a nucleotide, a cell penetrating peptide moiety, an amino acid, a formamidinyl moiety, and acyl;
- and,
- Rz is selected from the group consisting of null, hydrogen, a C1-C6 alkyl, and acyl;
- and pharmaceutically acceptable salts thereof.
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An antisense oligonucleotide comprising a repeated three nucleotide sequence having the formula:
- Wherein:
- Nu1, Nu2 and Nu3 are nucleobases selected from the group consisting of adenine, guanine, thymine, uracil, cytosine, and hypoxanthine;
- n is from about 3 to about 10 representing the number of repeats of the nucleotide sequence (Nu1, Nu2, Nu3);
- R1 is —N(Me)2
- Rx is selected from the group consisting of HO—, a nucleotide, and piperazinyl;
- Ry is selected from the group consisting of hydrogen, a C1-C6 alkyl, a nucleotide, a cell penetrating peptide moiety, an amino acid, a formamidinyl moiety, and acyl;
- and,
- Rz is selected from the group consisting of null, hydrogen, a C1-C6 alkyl, and acyl;
- and pharmaceutically acceptable salts thereof.
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Dependencies are inferred from the claim text.