Modulation of CGG triplet repeat binding protein 1 expression

• US 20040101852A1
• Filed: 11/21/2002
• Published: 05/27/2004
• Est. Priority Date: 11/21/2002
• Status: Abandoned Application

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Dobie, Kenneth W., Dean, Nicholas M., Bennett, C. Frank
• Application Number:
  US10/303,566
• Publication Number:
  US 20040101852A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy

Abstract

Compounds, compositions and methods are provided for modulating the expression of CGG triplet repeat binding protein 1. The compositions comprise oligonucleotides, targeted to nucleic acid encoding CGG triplet repeat binding protein 1. Methods of using these compounds for modulation of CGG triplet repeat binding protein 1 expression and for diagnosis and treatment of disease associated with expression of CGG triplet repeat binding protein 1 are provided.

Claims

1. A compound 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding CGG triplet repeat binding protein 1, wherein said compound specifically hybridizes with said nucleic acid molecule encoding CGG triplet repeat binding protein 1 (SEQ ID NO:

4) and inhibits the expression of CGG triplet repeat binding protein 1.

2. The compound of claim 1 comprising 12 to 50 nucleobases in length.

3. The compound of claim 2 comprising 15 to 30 nucleobases in length.

4. The compound of claim 1 comprising an oligonucleotide.

5. The compound of claim 4 comprising an antisense oligonucleotide.

6. The compound of claim 4 comprising a DNA oligonucleotide.

7. The compound of claim 4 comprising an RNA oligonucleotide.

8. The compound of claim 4 comprising a chimeric oligonucleotide.

9. The compound of claim 4 wherein at least a portion of said compound hybridizes with RNA to form an oligonucleotide-RNA duplex.

10. The compound of claim 1 having at least 70% complementarity with a nucleic acid molecule encoding CGG triplet repeat binding protein 1 (SEQ ID NO:

4) said compound specifically hybridizing to and inhibiting the expression of CGG triplet repeat binding protein 1.

11. The compound of claim 1 having at least 80% complementarity with a nucleic acid molecule encoding CGG triplet repeat binding protein 1 (SEQ ID NO:

4) said compound specifically hybridizing to and inhibiting the expression of CGG triplet repeat binding protein 1.

12. The compound of claim 1 having at least 90% complementarity with a nucleic acid molecule encoding CGG triplet repeat binding protein 1 (SEQ ID NO:

4) said compound specifically hybridizing to and inhibiting the expression of CGG triplet repeat binding protein 1.

13. The compound of claim 1 having at least 95% complementarity with a nucleic acid molecule encoding CGG triplet repeat binding protein 1 (SEQ ID NO:

4) said compound specifically hybridizing to and inhibiting the expression of CGG triplet repeat binding protein 1.

14. The compound of claim 1 having at least one modified internucleoside linkage, sugar moiety, or nucleobase.

15. The compound of claim 1 having at least one 2′

-O-methoxyethyl sugar moiety.

16. The compound of claim 1 having at least one phosphorothioate internucleoside linkage.

17. The compound of claim 1 having at least one 5-methylcytosine.

18. A method of inhibiting the expression of CGG triplet repeat binding protein 1 in cells or tissues comprising contacting said cells or tissues with the compound of claim 1 so that expression of CGG triplet repeat binding protein 1 is inhibited.

22. A kit or assay device comprising the compound of claim 1.

23. A method of treating an animal having a disease or condition associated with CGG triplet repeat binding protein 1 comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of claim 1 so that expression of CGG triplet repeat binding protein 1 is inhibited.

24. The method of claim 23 wherein the disease or condition is a neurodegenerative disease.

19. A method of screening for a modulator of CGG triplet repeat binding protein 1, the method comprising the steps of:

a. contacting a preferred target segment of a nucleic acid molecule encoding CGG triplet repeat binding protein 1 with one or more candidate modulators of CGG triplet repeat binding protein 1, and

b. identifying one or more modulators of CGG triplet repeat binding protein 1 expression which modulate the expression of CGG triplet repeat binding protein 1.

20. The method of claim 19 wherein the modulator of CGG triplet repeat binding protein 1 expression comprises an oligonucleotide, an antisense oligonucleotide, a DNA oligonucleotide, an RNA oligonucleotide, an RNA oligonucleotide having at least a portion of said RNA oligonucleotide capable of hybridizing with RNA to form an oligonucleotide-RNA duplex, or a chimeric oligonucleotide.

21. A diagnostic method for identifying a disease state comprising identifying the presence of CGG triplet repeat binding protein 1 in a sample using at least one of the primers comprising SEQ ID NOs:

5 or 6, or the probe comprising SEQ ID NO;

7.