NUCLEIC ACID LIGANDS AGAINST INFECTIOUS PRIONS

• US 20110104668A1
• Filed: 11/03/2009
• Published: 05/05/2011
• Est. Priority Date: 11/03/2009
• Status: Active Grant

• Current Assignee: Vivonics Inc.
• Original Assignee: Infoscitex
• Inventors: Gilman, Vladimir Leo
• Granted Patent: US 8,841,429 B2
• 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: C07K 14/47 from mammals
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/16 Aptamers
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2525/205 Aptamer
• CPC Class Codes: G01N 2800/28 Neurological disorders
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds

Abstract

The invention generally relates to nucleic acid ligands that specifically bind to infectious prions, and methods of diagnosing a transmissible spongiform encephalopathy disease in a subject. In certain embodiments, the invention provides an isolated nucleic acid ligand that binds to an infectious prion. In other embodiments, the invention provides a method for diagnosing a transmissible spongiform encephalopathy disease in a subject including obtaining a tissue or body fluid sample from a subject, contacting the tissue or body fluid with a nucleic acid ligand that binds to an infectious prion, thereby detecting the infectious prion in the sample, and diagnosing the transmissible spongiform encephalopathy disease based on results of the contacting step.

Claims

1. An isolated nucleic acid ligand that binds to an infectious prion.

2. The nucleic acid ligand according to claim 1, wherein the nucleic acid ligand is single stranded.

3. The nucleic acid ligand according to claim 1, wherein the nucleic acid ligand is DNA.

4. The nucleic acid ligand according to claim 1, wherein the nucleic acid ligand is RNA.

5. The nucleic acid ligand according to claim 1, wherein the nucleic acid ligand comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:

1 and SEQ ID NO;

2.

6. The nucleic acid ligand according to claim 1, wherein the nucleic acid ligand comprises an RNA sequence transcribed from a nucleotide sequence selected from the group consisting of SEQ ID NO:

1 and SEQ ID NO;

2.

7. The nucleic acid ligand according to claim 1, further comprising a detectable label.

8. The nucleic acid ligand according to claim 7, wherein the detectable label is a fluorescent label.

9. A method for diagnosing a transmissible spongiform encephalopathy disease in a subject comprising:

providing a tissue or body fluid sample from a subject;

contacting the tissue or body fluid with a nucleic acid ligand that binds to an infectious prion, thereby detecting the infectious prion in the sample; and

diagnosing the transmissible spongiform encephalopathy disease based on results of the contacting step.

10. The method according to claim 9, wherein the nucleic acid ligand is single.

11. The method according to claim 9, wherein the nucleic acid ligand is DNA.

12. The method according to claim 9, wherein the nucleic acid ligand is RNA.

13. The method according to claim 9, wherein the nucleic acid ligand comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:

1 and SEQ ID NO;

2.

14. The method according to claim 9, wherein the nucleic acid ligand comprises an RNA sequence transcribed from a nucleotide sequence selected from the group consisting of SEQ Id NO:

1 and SEQ ID NO;

2.

15. The method according to claim 9, wherein the subject is a human.

16. The method according to claim 15, wherein the transmissible spongiform encephalopathy disease is selected from the group consisting of:

Creutzfeldt-Jakob Disease (CJD);

Variant Creutzfeldt-Jakob Disease (vCJD);

Gerstmann-Straussler-Scheinker Syndrome;

Fatal Familial Insomnia; and

Kuru.

17. The method according to claim 9, wherein the subject is an animal.

18. The method according to claim 17, wherein the transmissible spongiform encephalopathy disease is selected from the group consisting of:

Bovine Spongiform Encephalopathy (BSE);

Chronic Wasting Disease (CWD);

Scrapie;

Transmissible mink encephalopathy;

Feline spongiform encephalopathy; and

Ungulate spongiform encephalopathy.

19. An isolated nucleotide sequence comprising SEQ ID NO:

1 or a nucleotide sequence substantially identical thereto.

20. The isolated nucleotide sequence according to claim 19, further comprising a detectable label.

21. The isolated nucleotide sequence according to claim 20, wherein the detectable label is a fluorescent label.

22. The isolated nucleotide sequence according to claim 19, wherein the sequence binds to an infectious prion.

23. A polypeptide encoded by the nucleotide sequence according to claim 19.

24. A vector comprising the nucleotide sequence according to claim 19 operably linked to an expression control element.

25. An isolated host cell transformed with a vector comprising the nucleotide sequence according to claim 19.

26. An isolated nucleotide sequence that hybridizes to the nucleotide sequence according to claim 19 under high stringency conditions.

27. An isolated nucleotide sequence that is complementary to the nucleotide sequence according to claim 19.

28. An isolated nucleotide sequence comprising SEQ ID NO:

2 or a nucleotide sequence substantially identical thereto.

29. The isolated nucleotide sequence according to claim 28, further comprising a detectable label.

30. The isolated nucleotide sequence according to claim 29, wherein the detectable label is a fluorescent label.

31. The isolated nucleotide sequence according to claim 28, wherein the sequence binds to an infectious prion.

32. A polypeptide encoded by the nucleotide sequence according to claim 28.

33. A vector comprising the nucleotide sequence according to claim 28 operably linked to an expression control element.

34. An isolated host cell transformed with a vector comprising the nucleotide sequence according to claim 28.

35. An isolated nucleotide sequence that hybridizes to the nucleotide sequence according to claim 28 under high stringency conditions.

36. An isolated nucleotide sequence that is complementary to the nucleotide sequence according to claim 28.