Nucleic acid probe libraries

• US 6,830,890 B2
• Filed: 10/22/2002
• Issued: 12/14/2004
• Est. Priority Date: 10/24/1994
• Status: Expired due to Fees

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Lockhart, David J., Vetter, Dirk, Diggelmann, Martin
• Primary Examiner(s): Ponnaluri, Padmashri
• Application Number:
  US10/278,970
• Publication Number:
  US 20030049674A1
• Time in Patent Office: 784 Days
• Field of Search: 435/6, 435/7.1, 435/DIG.1, 435/DIG.14, 435/DIG.37, 435/DIG.40, 436/518, 530/413, 536/55, 536/58, 536/123, 536/23.1, 536/25.3, 536/24.3
• US Class Current: 506/3
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00635 by reactive plasma treatment
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C12N 15/1093 General methods of preparing gene libraries, not provided for in other subgroups
• CPC Class Codes: C12Q 1/6811 Selection methods for production or design of target specific oligonucleotides or binding molecules
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2525/205 Aptamer
• CPC Class Codes: C12Q 2565/525 characterised by the capture oligonucleotide being double stranded
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: G01N 33/5308 : for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/551 : the carrier being inorganic

Abstract

Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

Claims

1. A method of screening a sample for a species capable of binding to a double-stranded nucleic acid comprising:

contacting said sample with a solid support comprising a plurality of different unimolecular double-stranded nucleic acids attached to known locations of the support, each of said attached nucleic acids independently having the formula;

2. A method in accordance with claim 1, wherein said species is a member selected from the group consisting of a drug, a protein and RNA molecule.

3. The method of claim 1, wherein the double-stranded nucleic acid is DNA.

4. The method of claim 1, wherein the double-stranded nucleic acid is RNA.

5. The method of claim 3, wherein the double-stranded nucleic acid includes suppressor, enhancer, or promoter sequence.

6. The method of claim 4, wherein the double-stranded RNA includes a region of a viral genome.

7. The method of claim 1, wherein the linking group is polyethylene glycol.

8. The method of claim 1, wherein the linking group comprises nucleotides.

9. The method of claim 1, wherein between 2 and 100 distinct nucleic acids are attached to the support.

10. The method of claim 1, wherein between 100 and 10,000 distinct nucleic acids are attached to the support.

11. The method of claim 1, wherein between 10,000 and 1,000,000 distinct nucleic acids are attached to the support.

12. The method of claim 1, wherein more than 100 distinct nucleic acids are attached to a square centimeter of the support.

13. The method of claim 1, wherein more than 1,000 distinct nucleic acids are attached to a square centimeter of the support.

14. The method of claim 1, wherein more than 10,000 distinct nucleic acids are attached to a square centimeter of the support.

15. A method of screening a sample for a species capable of binding to a conformationally-restricted probe comprising:

contacting said sample with a solid support comprising a plurality of different conformationally-restricted probes attached to known locations of said support, each of said restricted probes independently having the formula;