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|Title:||High affinity HIV Nucleocapsid nucleic acid ligands|
|Abstract:||Methods are described for the identification and preparation of high-affinity nucleic acid ligands to HIV-1 nucleocapsid. Included in the invention are specific RNA ligands to HIV-1 nucleocapsid identified by the SELEX method. Also included are RNA ligands that inhibit the function of HIV-1 nucleocapsid.|
|Inventor(s):||Allen; Patrick Nikita (Boulder, CO), Gold; Larry (Boulder, CO)|
|Assignee:||NeXstar Pharmaceuticals, Inc. (Boulder, CO)|
|Filing Date:||Jun 07, 1995|
|Claims:||1. A method for identifying nucleic acid ligands to nucleocapsid comprising: |
a) preparing a candidate mixture of nucleic acids;
b) contacting the candidate mixture of nucleic acids with nucleocapsid, wherein nucleic acids having an increased affinity to nucleocapsid relative to the candidate mixture may by 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 acid sequences with relatively higher affinity and specificity for binding to nucleocapsid, whereby nucleic acid ligands of nucleocapsid 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 the candidate mixture contacted includes non-amplifiable random pool nucleic acids.
4. The method of claim 1 wherein said candidate mixture of nucleic acids is comprised of single stranded nucleic acids.
5. The method of claim 4 wherein said single stranded nucleic acids are ribonucleic acids.
6. The method of claim 4 wherein said single stranded nucleic acids are deoxyribonucleic acids.
7. The method of claim 5 wherein said candidate mixture of nucleic acids comprises 2'-amino (2'-NH.sub.2) modified ribonucleic acids.
8. The method of claim 1 wherein said nucleocapsid is HIV-1 nucleocapsid.