Methods and compositions involving miRNA and miRNA inhibitor molecules
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07H-021/04
C12N-015/11
C12N-015/113
C12Q-001/68
A61K-009/127
A61K-031/7088
출원번호
US-0254532
(2014-04-16)
등록번호
US-9051571
(2015-06-09)
발명자
/ 주소
Brown, David
Ford, Lance
Cheng, Angie
Jarvis, Rich
Byrom, Mike
Ovcharenko, Dmitriy
Devroe, Eric
Kelnar, Kevin
출원인 / 주소
Asuragen, Inc.
대리인 / 주소
Nutter McClennen & Fish LLP
인용정보
피인용 횟수 :
1인용 특허 :
94
초록▼
The present invention concerns methods and compositions for introducing miRNA activity or function into cells using synthetic nucleic acid molecules. Moreover, the present invention concerns methods and compositions for identifying miRNAs with specific cellular functions that are relevant to therape
The present invention concerns methods and compositions for introducing miRNA activity or function into cells using synthetic nucleic acid molecules. Moreover, the present invention concerns methods and compositions for identifying miRNAs with specific cellular functions that are relevant to therapeutic, diagnostic, and prognostic applications wherein synthetic miRNAs and/or miRNA inhibitors are used in library screening assays.
대표청구항▼
1. A synthetic RNA molecule comprising: a) a first 15-25 residue oligonucleotide having a sequence that is 80-100% identical to a mature miR-7 sequence;b) a second 15-25 residue oligonucleoLide having a sequence that is 60-100% identical to a sequence complementary to the mature miR-7 sequence; andc
1. A synthetic RNA molecule comprising: a) a first 15-25 residue oligonucleotide having a sequence that is 80-100% identical to a mature miR-7 sequence;b) a second 15-25 residue oligonucleoLide having a sequence that is 60-100% identical to a sequence complementary to the mature miR-7 sequence; andc) at least one ofi) a replacement group for the phosphate or the hydroxyl of the nucleotide at the 5′ end of the second oligonucleotide, andii) one or more sugar modifications in the first or last 1-6 residues of the second oligonucleotide. 2. The synthetic RNA molecule of claim 1, comprising a replacement group for the phosphate or the hydroxyl of the nucleotide at the 5′ end of the second oligonucleotide. 3. The synthetic RNA molecule of claim 2, wherein the replacement group is biotin, an amine group, a lower alkylamine group, an acetyl group, 2′O-Me, DMTO, fluoroscein, a thiol, or acridine. 4. The synthetic RNA molecule of claim 2, wherein the phosphate of the nucleotide at the 5′ end of the second oligonucleotide is replaced. 5. The synthetic RNA molecule of claim 4, wherein the replacement group is a lower alkylamine group. 6. The synthetic RNA molecule of claim 2, wherein the hydroxyl of the nucleotide at the 5′ end of the second oligonucleotide is replaced. 7. The synthetic RNA molecule of claim 1, comprising one or more sugar modifications in the first or last 1-6 residues of the second oligonucleotide. 8. The synthetic RNA molecule of claim 7, wherein the sugar modification is a 2′O-Me modification. 9. The synthetic RNA molecule of claim 7, comprising one or more sugar modifications in the first 1-6 residues of the second oligonucleotide. 10. The synthetic RNA molecule of claim 7, comprising one or more sugar modifications in the last 1-6 residues of the second oligonucleotide. 11. The synthetic RNA molecule of claim 7, comprising one or more sugar modifications in the first or last 2 to 4 residues of the second oligonucleotide. 12. The synthetic RNA molecule of claim 1, further comprising a noncomplementarity between one or more nucleotide in the last 1-5 residues at the 3′ end of the second oligonucleotide and the corresponding nucleotides of the First oligonucleotide. 13. The synthetic RNA molecules of claim 1, further comprising a noncomplementarity between two or more nucleotides in the last 1-5 residues at the 3′ end of the second oligonucleotide and the corresponding nucleotides of the first oligonucleotide. 14. The synthetic RNA molecule of claim 1, comprising i) and ii). 15. The synthetic RNA molecule of claim 12, comprising i) and ii). 16. The synthetic RNA molecule of claim 1, wherein time first oligonucleotide is 90-100% identical to the mature miR-7 sequence. 17. The synthetic RNA molecule of claim 1, wherein the first oligonucleotide is 100% identical to the mature miR-7 sequence. 18. A pharmaceutical composition comprising the synthetic RNA of claim 1 and a liposomal delivery vehicle. 19. A method of reducing lung cancer cell viability or inducing apoptosis in a lung cancer cell comprising introducing into the lung cancer cell an effective amount of a synthetic RNA molecule comprising: a) a first 15-25 residue oligonucleotide having a sequence that is 80-100% identical to a mature miR-7 sequence; andb) a second 15-25 residue oligonucleotide having a sequence that is 60-100% identical to a sequence complementary to the mature miR-7 sequence; andc) at least one ofi) a replacement group for the phosphate or the hydroxyl of the nucleotide at the 5′ end of the second oligonucleotide, andii) one or more sugar modifications in the first or last 1-6 residues of the second oligonucleotide. 20. The method of claim 19, wherein: i) the phosphate or the nucleotide at the 5′ end of the second oligonucleotide is replaced with a lower alkylamine group, orii) one or more sugar in the first or last 1-6 residues of the second oligonucleotide has a 2′O-Me modification. 21. The method of claim 19, wherein the cancer cell is a human cell. 22. The method of claim 19, wherein the cancer cell is in a human. 23. A method of treating lung cancer comprising introducing into a lung cancer cell an effective amount of a synthetic RNA molecule comprising: a) a first 15-25 residue oligonucleotide having a sequence that is 80-100% identical to a mature miR-7 sequence; anda second 15-25 residue oligonucleotide having a sequence that is 60-100% identical to a sequence complementary to the mature miR-7 sequence; andc) at least one ofi) a replacement group for the phosphate or the hydroxyl of the nucleotide at the 5′ end of the second oligonucleotide, andii) one or more sugar modifications in the first or last 1-6 residues of the second oligonucleotide. 24. The method of claim 23, wherein: i) the phosphate of the nucleotide at the 5′ end of the second oligonucleotide is replaced with a lower alkylamine group, orii) one or more sugar in the first or last 1-6 residues of the second oligonucleotide has a 2′O-Me modification. 25. The method of claim 23, wherein the cancer cell is a human cell. 26. The method of claim 23, wherein the cancer cell is in a human. 27. The method or claim 19, wherein the first oligonucleotide is 100% identical to the mature miR-7 sequence. 28. The method or claim 23, wherein the first oligonucleotide is 100% identical to the mature miR-7 sequence.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (94)
Lee Linda ; Benson Scott C. ; Rosenblum Barnett B. ; Spurgeon Sandra L., 4, 7-Dichlororhodamine dyes.
Menchen Steven M. (Fremont CA) Lee Linda G. (Palo Alto CA) Connell Charles R. (Redwood City CA) Hershey N. Davis (San Carlos CA) Chakerian Vergine (San Mateo CA) Woo Sam (Redwood City CA) Fung Steven, 4,7-dichlorofluorescein dyes as molecular probes.
Milburn Susan C. (Austin TX) Goldrick Marianna (Pflugerville TX) Winkler Matthew (Austin TX), Compositions and methods for increasing the yields of in vitro RNA transcription and other polynucleotide synthetic reac.
Milburn, Susan C.; Goldrick, Marianna; Winkler, Matthew, Compositions and methods for increasing the yields of in vitro RNA transcription and other polynucleotide synthetic reactions.
Milburn, Susan; Goldrick, Marianna; Winkler, Matthew, Compositions and methods for increasing the yields of the in vitro RNA transcription and other polynucleotide synthetic reactions.
Von Wronski,Mathew A.; Marinelli,Edmund R.; Nunn,Adrian D.; Pillai,Radhakrishna; Ramalingam,Kondareddiar; Tweedle,Michael F.; Linder,Karen; Nanjappan,Palaniappa; Raju,Natarajan, Compounds for targeting endothelial cells, compositions containing the same and methods for their use.
Sobol Robert E. (LaJolla CA) Green Mark R. (San Diego CA) Kawasaki Ernest S. (Richmond CA), Detection of carcinoma metastases by nucleic acid amplification.
Maruyama,Toshiaki; Frederickson,Shana; Bowdish,Katherine S.; Renshaw,Mark; Lin,Ying Chi, Engineered templates and their use in single primer amplification.
Lockhart David J. ; Brown Eugene L. ; Wong Gordon G. ; Chee Mark S. ; Gingeras Thomas R., Expression monitoring by hybridization to high density oligonucleotide arrays.
Sedlacek Hans-Harald,DEX ; Bosslet Klaus,DEX ; Muller Rolf,DEX, Gene therapy of tumors with an endothelial cell-specific, cell cycle-dependent active compound.
Jonathan Marc Rothberg ; Michael W. Deem ; John W. Simpson, Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing.
Rothberg Jonathan Marc ; Deem Michael W. ; Simpson John W., Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing.
Livak Kenneth J. (San Jose CA) Flood Susan J. A. (Fremont CA) Marmaro Jeffrey (Foster City CA), Method for detecting nucleic acid amplification using self-quenching fluorescence probe.
Lloyd,John Scott; Weston,Anthony; Cardy,Donald Leonard Nicholas, Method for detecting nucleic acid target sequences involving in vitro transcription from an RNA polymerase promoter.
Benner Steven A. (Hadlaubstrasse 151 CH-8006 Zurich CHX), Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases.
van Gemen, Bob; Timmermans, Eveline Catherina A. C.; de Ronde, Anthonij; Dobbelaer, Irene Johanna M., Method of determining therapeutic activity and/or possible side-effects of a medicament.
Dai,Hongyue; He,Yudong; Linsley,Peter S.; Mao,Mao; Roberts,Christopher J.; Van't Veer,Laura Johanna; Van de Vijver,Marc J.; Bernards,Rene; Hart,A. A. M., Methods of assigning treatment to breast cancer patients.
Huang,Mingxian; Wu,Lei; Wang,Xiaobo; Xu,Junquan; Tao,Guo Liang; Rothwarf,David M., Microdevices having a preferential axis of magnetization and uses thereof.
David J. Lockhart ; Mark Chee ; Kevin Gunderson ; Lai Chaoqiang ; Lisa Wodicka ; Maureen T. Cronin ; Danny Lee ; Huu M. Tran ; Hajime Matsuzaki, Nucleic acid analysis techniques.
Duck Peter (Ottawa CAX) Bender Robert (Ottawa CAX) Crosby William (Saskatoon CAX) Robertson John G. (L\Ange Gardien CAX), Nucleic acid compositions with scissile linkage useful for detecting nucleic acid sequences.
Keys, Daniel A.; Farooqui, Firdous; Reddy, M. Parameswara, Oligonucleotide probes for detecting nucleic acids through changes in flourescence resonance energy transfer.
Van Gelder Russell N. (2200 Divot Dr. Crystal Lake MD 63131) Von Zastrow Mark E. (11570 Buena Vista Dr. Los Altos CA 94022) Barchas Jack D. (1900 Rittenhouse Sq. #18A Philadelphia PA 19103) Eberwine , Process for amplifying a target polynucleotide sequence using a single primer-promoter complex.
Bergot B. John (Redwood City CA) Chakerian Vergine (San Mateo CA) Connell Charles R. (Redwood City CA) Eadie J. Scott (Indianapolis IN) Fung Steven (Palo Alto CA) Hershey N. Davis (San Carlos CA) Lee, Spectrally resolvable rhodamine dyes for nucleic acid sequence determination.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.