High affinity TGF.beta. nucleic acid ligands and inhibitors
First Claim
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1. A nucleic acid ligand to transforming growth factor-beta (TGFβ
- ) identified according to a method comprising;
a) preparing a candidate mixture of nucleic acids;
b) contacting the candidate mixture of nucleic acids with TGFβ
, wherein nucleic acids having an increased affinity to TGFβ
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 TGFβ
, whereby said nucleic acid ligand of TGFβ
may be identified.
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Abstract
Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGFβ. Included in the invention are specific RNA and ssDNA ligands to TGFβ1 identified by the SELEX method. Also included are RNA ligands that inhibit the interaction of TGFβ1 with its receptor.
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Citations
11 Claims
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1. A nucleic acid ligand to transforming growth factor-beta (TGFβ
- ) identified according to a method comprising;
a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with TGFβ
, wherein nucleic acids having an increased affinity to TGFβ
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 TGFβ
, whereby said nucleic acid ligand of TGFβ
may be identified. - View Dependent Claims (4, 5, 6, 10, 11)
- ) identified according to a method comprising;
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2. A nucleic acid ligand to transforming growth factor-beta 1 (TFGβ
- 1) identified according to a method comprising;
a) preparing a candidate mixture of nucleic acids; b) contacting the candidate mixture of nucleic acids with TGFβ
1, wherein nucleic acids having an increased affinity to TGFβ
1 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 TGFβ
1, whereby said nucleic acid ligand of TGFβ
1 may be identified.
- 1) identified according to a method comprising;
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3. A purified and isolated non-naturally occurring RNA ligand to TGFβ
- 1 wherein said ligand is selected from the group consisting of the sequences set forth in Table 3 (SEQ ID NOS;
12-42).
- 1 wherein said ligand is selected from the group consisting of the sequences set forth in Table 3 (SEQ ID NOS;
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7. A purified and isolated non-naturally occurring ssDNA ligand to TGFβ
- 1 wherein said ligand is selected from the group consisting of the sequences set forth in Table 6 (SEQ ID NOS;
55-89).
- 1 wherein said ligand is selected from the group consisting of the sequences set forth in Table 6 (SEQ ID NOS;
-
8. A purified and isolated non-naturally occurring nucleic acid ligand to transforming growth factor-beta (TGFβ
- ).
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9. A purified and isolated non-naturally occurring nucleic acid ligand to transforming growth factor-beta 1 (TGFβ
- 1).
Specification