Details for Patent: 5,849,890

Title:	High affinity oligonucleotide ligands to chorionic gonadotropin hormone and related glycoprotein hormones
Abstract:	Methods are described for the identification and preparation of nucleic acid ligands to CG-related glycoprotein hormones. Included in the invention are specific RNA ligands to hCG and hTSH identified by the SELEX method.
Inventor(s):	Gold; Larry (Boulder, CO), Jayasena; Sumedha D. (Boulder, CO), Nieuwlandt; Dan (Broomfield, CO), Davis; Ken (Los Altos, CA)
Assignee:	NeXstar Pharmaceuticals, Inc. (Boulder, CO)
Filing Date:	Jun 07, 1995
Application Number:	08/484,552
Claims:	1. A purified and isolated non-naturally occurring nucleic acid ligand to a chorionic gonadotropin (CG)-related glycoprotein hormone. 2. The nucleic acid ligand to a CG-related glycoprotein hormone of claim 1 identified according to the method comprising: a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with a CG-related glycoprotein hormone, wherein nucleic acids having an increased affinity to the CG-related glycoprotein hormone 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 acid sequences with relatively higher affinity and specificity for binding to the CG-related glycoprotein hormone, whereby nucleic acid ligands of the CG-related glycoprotein hormone may be identified. 3. The nucleic acid ligand to a CG-related glycoprotein hormone of claim 2 wherein the method further comprises contacting the increased affinity nucleic acids with one or more non-target molecules, wherein nucleic acids with affinity to the non-target molecule(s) are removed, and wherein the non-target molecule is a member of the CG-related glycoprotein hormone family other than the one for which increased affinity nucleic acids are being selected. 4. A purified and isolated non-naturally occurring nucleic acid ligand to an hCG-related glycoprotein hormone. 5. The nucleic acid ligand to an hCG-related glycoprotein hormone of claim 4 identified according to the method comprising: a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with an hCG-related glycoprotein hormone, wherein nucleic acids having an increased affinity to the hCG-related glycoprotein hormone 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 acid sequences with relatively higher affinity and specificity for binding to the hCG-related glycoprotein hormone, whereby nucleic acid ligands of the hCG-related glycoprotein hormone may be identified. 6. The nucleic acid ligand to an hCG-related glycoprotein hormone of claim 5 wherein the method further comprises contacting the increased affinity nucleic acids with one or more non-target molecules, wherein nucleic acids with affinity to the non-target molecule(s) are removed, and wherein the non-target molecule is a member of the hCG-related glycoprotein hormone family other than the one for which increased affinity nucleic acids are being selected. 7. The purified and isolated non-naturally occurring nucleic acid ligand of claim 4, wherein said hCG-related glycoprotein hormone is hCG, and wherein said ligand is an RNA selected from the group consisting of the sequences set forth in FIGS. 3 and 4 and Tables 2, 5, 11 and 13 (SEQ ID NOS:4-30, 34-35, 41, 80-169). 8. The purified and isolated non-naturally occurring nucleic acid ligand of claim 4, wherein said hCG-related glycoprotein hormone is hTSH, and wherein said ligand is an RNA selected from the group consisting of the sequences set forth in Table 7 (SEQ ID NOS:42-63). 9. The purified and isolated non-naturally occurring nucleic acid ligand of claim 5, wherein said hCG-related glycoprotein hormone is hCG. 10. The purified and isolated non-naturally occurring nucleic acid ligand of claim 5, wherein said hCG-related glycoprotein hormone is hTSH.