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Details for Patent: 5,587,468

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Details for Patent: 5,587,468

Title: High affinity nucleic acid ligands to HIV integrase
Abstract:Methods are described for the identification and preparation of nucleic acid ligands to HIV integrase. Included in the invention are specific RNA ligands to HIV integrase identified by the SELEX method. Also included in the invention are specific RNA ligands that are inhibitors of HIV integrase.
Inventor(s): Allen; Patrick (Boulder, CO), Gold; Larry (Boulder, CO)
Assignee: University Research Corporation (Boulder, CO)
Filing Date:May 16, 1995
Application Number:08/442,572
Claims:1. A purified and isolated non-naturally occurring nucleic acid ligand to HIV integrase.

2. The purified and isolated non-naturally occurring nucleic acid ligand of claim 1 wherein said HIV integrase is HIV-1 integrase.

3. The purified and isolated non-naturally occurring nucleic acid ligand of claim 2 wherein said nucleic acid ligand is single-stranded.

4. The purified and isolated non-naturally occurring nucleic acid ligand of claim 3 wherein said nucleic acid ligand is RNA.

5. The purified and isolated non-naturally occurring nucleic acid ligand of claim 3 wherein said nucleic acid ligand is DNA.

6. The purified and isolated non-naturally occurring RNA ligand to HIV-1 integrase of claim 4 wherein said ligand is selected from the group consisting of the sequences set forth in Table 2.

7. The purified and isolated non-naturally occurring RNA ligand of claim 4 wherein said ligand is comprised of 2'-amino(2'-NH.sub.2) modified nucleotides.

8. A nucleic acid ligand to HIV integrase identified according to the method comprising:

a) contacting a candidate mixture of nucleic acids with HIV integrase, wherein nucleic acids having an increased affinity to HIV integrase relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acid sequences with relatively higher affinity and specificity for binding to HIV integrase, whereby a nucleic acid ligand of HIV integrase may be identified.

9. The nucleic acid ligand of claim 8 wherein the candidate mixture contacted includes non-amplifiable random pool nucleic acids.

10. The nucleic acid ligand of claim 8 wherein said HIV integrase is HIV-1 integrase.

11. The nucleic acid ligand of claim 10 wherein said candidate mixture contacted includes non-amplifiable random pool nucleic acids.

12. The nucleic acid ligand of claim 8 wherein said ligand is an inhibitor of HIV integrase.

13. The nucleic acid ligand of claim 9 wherein said ligand is an inhibitor of HIV integrase.

14. The nucleic acid ligand of claim 10 wherein said ligand is an inhibitor of HIV-1 integrase.

15. The nucleic acid ligand of claim 11 wherein said ligand is an inhibitor of HIV-1 integrase.

16. The nucleic acid ligand of claim 11 wherein said ligand is comprised of 2'-amino (2'-NH.sub.2) modified nucleotides.
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