|Title:||High affinity HIV-1 gag nucleic acid ligands|
|Abstract:||Methods are described for the identification and preparation of high-affinity nucleic acid ligands to HIV-1 GAG, Included in the invention are specific RNA ligands to HIV-1 GAG identified by the SELEX method, Also included are RNA ligands that inhibit the function of HIV-1 GAG.|
|Inventor(s):||Lochrie; Michael A. (Boulder, CO), Gold; Larry (Boulder, CO)|
|Assignee:||NeXstar Pharmaceuticals, Inc. (Boulder, CO)|
|Filing Date:||May 19, 1995|
|Claims:||1. A method for identifying nucleic acid ligands to HIV-1 GAG, comprising: |
a) preparing a candidate mixture of nucleic acids;
b) contacting the candidate mixture of nucleic acids with HIV-1 GAG, wherein nucleic acids having an increased affinity to HIV-1 GAG relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;
c) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and
d) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acids with relatively higher affinity and specificity for binding to HIV-1 GAG, whereby nucleic acids ligands to HIV-1 GAG may be identified.
2. The method of claim 1 further comprising:
e) repeating steps b), c), and d).
3. The method of claim 1 wherein said candidate mixture of nucleic acids is comprised of single stranded nucleic acids.
4. The method of claim 3 wherein said single stranded nucleic acids are ribonucleic acids.
5. The method of claim 4 wherein said candidate mixture of nucleic acids comprises modified nucleic acids.
6. The method of claim 5 wherein said candidate mixture of nucleic acids comprises 2'-amino (2'-NH.sub.2) modified nucleic acids.
7. The method of claim 5 wherein said candidate mixture of nucleic acids comprises 2'-fluoro (2'-F) modified nucleic acids.
8. A nucleic acid ligand to HIV-1 GAG identified according to the method of claim 1.
9. A purified and isolated non-naturally occurring RNA ligand to HIV-1 GAG wherein said ligand is selected from the group consisting of the sequences set forth in SEQ ID NOS. 8-27 and 34-46.
10. A purified and isolated non-naturally occurring nucleic acid ligand to HIV-1 GAG.
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