Kinase suppressor of ras inactivation for therapy of ras mediated tumorigenesis
First Claim
1. An oligonucleotide which is substantially complementary to a region of KSR RNA, wherein said oligonucleotide inhibits the expression of KSR.
2 Assignments
0 Petitions
Accused Products
Abstract
The present invention relates to methods and compositions for the specific inhibition of kinase suppressor of Ras (KSR). In particular, the invention provides genetic approaches and nucleic acids for the specific inhibition of KSR, particularly of KSR expression. The invention relates to antisense oligonucleotides and the expression of nucleic acid which is substantially complementary to KSR RNA. Oligonucleotide and nucleic acid compositions are provided. The invention provides methods to inhibit KSR, including inhibition of KSR expression. Methods for blocking gf Ras mediated tumorigenesis, metastasis, and for cancer therapy are provided.
-
Citations
30 Claims
- 1. An oligonucleotide which is substantially complementary to a region of KSR RNA, wherein said oligonucleotide inhibits the expression of KSR.
-
4. An oligonucleotide which is substantially complementary to a translation initiation site, 5′
- untranslated region, coding region or 3′
untranslated region of mRNA encoding mammalian KSR.
- untranslated region, coding region or 3′
-
5. An antisense oligonucleotide comprising a sequence substantially complementary to the CA1 region of KSR.
-
6. An antisense oligonucleotide comprising a sequence substantially complementary to nucleotides 124 to 243 (SEQ ID NO:
- 1) of the coding sequence of KSR, or a portion thereof.
- View Dependent Claims (7)
-
8. An antisense oligonucleotide comprising a sequence selected from the group of SEQ ID NO:
- 6, SEQ ID NO;
7 and SEQ ID NO;
8.
- 6, SEQ ID NO;
- 12. A recombinant DNA molecule comprising a nucleic acid sequence which encodes on transcription an antisense RNA complementary to mammalian KSR RNA or a portion thereof.
-
15. An expression vector capable of expressing an nucleic acid which is substantially complementary to the coding sequence of KSR RNA, or a portion/fragment thereof, wherein said oligonucleotide/nucleic acid inhibits the expression of KSR.
-
16. An expression vector capable of expressing an oligonucleotide which is substantially complementary to the CA1 region of the coding sequence of KSR RNA, or a portion/fragment thereof, wherein said oligonucleotide inhibits the expression of KSR.
-
19. A composition comprising one or more chemotherapeutic or radiotherapeutic agent and an oligonucleotide which is targeted to a mRNA encoding mammalian KSR and which inhibits KSR expression.
-
20. A composition comprising an expression vector and a pharmaceutically acceptable carrier or diluent, wherein said expression vector is capable of expressing nucleic acid which is substantially complementary to the coding sequence of KSR RNA, or a portion/fragment thereof, wherein said nucleic acid inhibits the expression of KSR.
-
21. A method of inhibiting the expression of mammalian KSR comprising contacting cells which express KSR with an effective amount of a nucleic acid which is complementary to a portion of the mRNA encoding KSR.
- 23. A method of treating or preventing a hyperproliferative condition associated with the expression of gf-Ras or heightened expression of Ras in a mammal comprising administering to said mammal a therapeutically effective amount of a compound or agent which inhibits the expression of mammalian KSR protein.
-
25. A method of treating or preventing a hyperproliferative condition associated with the expression of gf-Ras or heightened expression of Ras in a mammal comprising expressing in said mammal or administering to said mammal a therapeutically effective amount of a nucleic acid which is complementary to a portion of the mRNA encoding KSR.
- 26. A method of treating or inhibiting the progression of cancer in a mammal comprising administering to a mammal a therapeutically effective amount of a compound or agent which inhibits the expression of mammalian KSR protein.
-
29. A method of identifying compounds or agents which inhibit the expression of KSR comprising the steps of:
-
(c) incubating a cell expressing KSR in the presence and absence of a candidate compound or agent; and
(d) detecting or measuring the expression of KSR in the presence and absence of a candidate compound or agent, whereby a decrease in the expression of KSR in the presence of said candidate compound or agent versus in the absence of said candidate compound or agent indicates that said compound or agent inhibits the expression of KSR.
-
-
30. A ribozyme that cleaves KSR mRNA.
Specification