|Title:|| Method for identification of high affinity nucleic acid ligands to selectins|
|Abstract:||This invention discloses high-affinity oligonucleotide ligands to lectins, specifically nucleic acid ligands having the ability to bind to the lectins, wheat germ agglutinin, L-selectin, E-selectin and P-selectin. Also disclosed are the methods for obtaining such ligands.|
|Inventor(s):|| Parma; David H. (Boulder, CO), Hicke; Brian James (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 and nucleic acid ligand sequences to a selectin comprising: |
a) contacting a candidate mixture of nucleic acids with a selectin, wherein nucleic acids having an increased affinity to said selectin 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 said selectin, whereby nucleic acid ligands of said selectin may be identified.
2. The method of claim 1 further comprising:
d) repeating steps a), b) and c).
3. The method of claim 1 wherein said candidate mixture 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 nucleic acids comprise modified ribonucleic acids.
6. The method of claim 5 wherein said nucleic acids comprise 2'-amino (2'NH.sub.2) modified nucleic acids.
7. The method of claim 3 wherein said single-stranded nucleic acids are deoxyribonucleic acids.
8. The method of claim 1 wherein said selectin is selected from the group consisting of L-selectin, E-selectin, and P-selectin.
9. The method of claim 6 wherein said selectin is L-selectin.