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|Title:||High-affinity oligonucleotide ligands to the tachykinin substance P|
|Abstract:||Methods are described for the identification and preparation of nucleic acid ligands to Substance P (SP). Included in the invention are specific RNA ligands to SP identified by the SELEX method.|
|Inventor(s):||Nieuwlandt; Dan T. (Boulder, CO), Gold; Larry (Boulder, CO), Wecker; Matthew (Boulder, CO)|
|Assignee:||NeXstar Pharmaceuticals, Inc. (Boulder, CO)|
|Filing Date:||May 16, 1995|
|Claims:||1. A nucleic acid ligand to Substance P (SP) identified according to a process comprising the steps of: |
a) contacting a candidate mixture of nucleic acids with SP, wherein nucleic acids having an increased affinity to the SP 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 in nucleic acids having increased affinity to SP, whereby a nucleic acid ligand of SP may be identified.
2. The nucleic acid ligand of claim 1 which is an RNA ligand, wherein the nucleotide sequence of said ligand is selected from the group consisting of the sequences set forth in FIGS. 2 and 3.
3. The RNA ligand of claim 2 wherein said ligand is selected from the group consisting of SEQ ID NOS:5, 18-21, 26-47 and 58.
4. The RNA ligand of claim 2 wherein said ligand is comprised of 2'-amino (2'-NH.sub.2) modified nucleotides.
5. A purified and isolated non-naturally occurring nucleic acid ligand to SP.
6. The nucleic acid ligand of claim 5 which is an RNA ligand.
7. The nucleic acid ligand of claim 1 wherein said ligand comprises 2'-amino (2'-NH.sub.2) modified nucleotides.