TAK1-D mediated induction of cell death in human cancer cells by specific sequence short double-stranded RNAS
원문보기
IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0361311
(2009-01-28)
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등록번호 |
US-8163709
(2012-04-24)
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발명자
/ 주소 |
- Kodym, Reinhard
- Story, Michael
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출원인 / 주소 |
- Board of Regents of the University of Texas System
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대리인 / 주소 |
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인용정보 |
피인용 횟수 :
1 인용 특허 :
0 |
초록
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The splicing variant D of the TAK1 gene is activated by short double-stranded RNAs in a sequence specific manner. Activation of TAK1-D leads to the downstream activation of the p38 MAPK and of SAPK/JNK but not the NFκB pathway. The current invention therefore provides a method of inducing apoptosis
The splicing variant D of the TAK1 gene is activated by short double-stranded RNAs in a sequence specific manner. Activation of TAK1-D leads to the downstream activation of the p38 MAPK and of SAPK/JNK but not the NFκB pathway. The current invention therefore provides a method of inducing apoptosis and/or cell cycle arrest in a cancer cell comprising contacting said cell with an agonist of Tak1-D function. The invention further provides a method of modulating inflammation and the treatment of cancer by the administration of an agonist of Tak1-D function or expression. In yet another aspect, the invention provides a method of inducing p38 MAPK and SAPK/JNK signaling in a cell comprising contacting said cell with an agonist of Tak1-D function or expression.
대표청구항
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1. A method of inducing apoptosis and/or cell cycle arrest in a lung cancer cell that expresses Tak1-D comprising contacting said cell with a double-stranded (ds) RNA directed to an mRNA for TLK1, wherein said dsRNA has the sequence NC(A/U)(A/U)(A/U)(A/U)GAX4-6AUGAN, wherein in N is any base or null
1. A method of inducing apoptosis and/or cell cycle arrest in a lung cancer cell that expresses Tak1-D comprising contacting said cell with a double-stranded (ds) RNA directed to an mRNA for TLK1, wherein said dsRNA has the sequence NC(A/U)(A/U)(A/U)(A/U)GAX4-6AUGAN, wherein in N is any base or null and X is any base, GGCUUUUGACCUUUAUGAA (SEQ ID NO: 1), CCAAAAGAAGAUGUGAUGA (SEQ ID NO:6), 5′-GGCUUUUGACCUUUAUGAAU-U (SEQ ID NO:7) or 3′-CCGAAAACUGGAAAUACUUA-A (SEQ ID NO:8). 2. The method of claim 1, wherein said dsRNA is encapsulated in a lipid vehicle. 3. The method of claim 1, wherein said cancer cell is a metastatic cancer cell, a recurrent cancer cell, a multi-drug resistant cancer cell. 4. The method of claim 1, further comprising contacting said cell with a second apoptosis-inducing agent. 5. The method of claim 4, wherein said second apoptosis-inducing agent is a chemotherapeutic, radiation, or a polypeptide inducer of apoptosis. 6. A method of treating a subject with lung cancer, cells of which express Tak 1-D, comprising administering to said subject a double-stranded (ds) RNA directed to an mRNA for TLK1, wherein said dsRNA has the sequence NC(A/U)(A/U)(A/U)(A/U)GAX4-6AUGAN, wherein in N is any base or null and X is any base, GGCUUUUGACCUUUAUGAA (SEQ ID NO: 1), CCAAAAGAAGAUGUGAUGA (SEQ ID NO:6), or 5′-GGCUUUUGACCUUUAUGAAU-U (SEQ ID NO:7) or 3′-CCGAAAACUGGAAAUACUUA-A (SEQ ID NO:8). 7. The method of claim 6, wherein said dsRNA is encapsulated in a lipid vehicle. 8. The method of claim 6, wherein said cancer is metastatic cancer, recurrent cancer, or a multi-drug resistant cancer cell. 9. The method of claim 6, further comprising contacting said cell with a second apoptosis-inducing agent. 10. The method of claim 9, wherein said second apoptosis-inducing agent is a chemotherapeutic, radiation, or a polypeptide inducer of apoptosis. 11. The method of claim 6, wherein said dsRNA is administered intratumorally, into tumor vasculature, loco-regional to a tumor, or systemically.
이 특허를 인용한 특허 (1)
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Zwart, Gerrit Townsend; Jones, Mark R.; Cooley, James, Collimator and energy degrader.
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