Riboswitches, methods for their use, and compositions for use with riboswitches
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C12Q-001/68
C12P-019/34
C12N-015/63
C07H-021/02
C07H-021/04
출원번호
US-0033174
(2011-02-23)
등록번호
US-8440810
(2013-05-14)
발명자
/ 주소
Breaker, Ronald R.
Nahvi, Ali
Sudarsan, Narasimhan
Ebert, Margaret S.
Winkler, Wade
Barrick, Jeffrey E.
Wickiser, John K.
출원인 / 주소
Yale University
대리인 / 주소
Pabst Patent Group LLP
인용정보
피인용 횟수 :
0인용 특허 :
112
초록▼
It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified
It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.
대표청구항▼
1. A method of inhibiting gene expression, the method comprising bringing into contact a compound and a cell,wherein the compound has the structure wherein, when the compound is bound to a guanine-responsive riboswitch, R7 serves as a hydrogen bond acceptor, R10 serves as a hydrogen bond donor, R11
1. A method of inhibiting gene expression, the method comprising bringing into contact a compound and a cell,wherein the compound has the structure wherein, when the compound is bound to a guanine-responsive riboswitch, R7 serves as a hydrogen bond acceptor, R10 serves as a hydrogen bond donor, R11 serves as a hydrogen bond acceptor, R12 serves as a hydrogen bond donor,wherein R13 is H, H2 or is not present,wherein R1, R3, R4, R5, R6, R8, and R9 are each independently C, N, O, or S,wherein R2, is C, N, O, S, C—NH2, C—NH—CH3, N—NH2, N—NH—CH3, or C, N, O, or S substituted with a group that serves as a hydrogen bond donor,wherein each independently represent a single or double bond,wherein the compound is not guanine, hypoxanthine, or xanthine,wherein the cell comprises a gene encoding an RNA comprising a guanine-responsive riboswitch, wherein the compound inhibits expression of the gene by binding to the guanine-responsive riboswitch. 2. The method of claim 1, wherein the cell is killed or growth of the cell is inhibited. 3. The method of claim 1, wherein the cell is a bacterial cell. 4. The method of claim 1, wherein the cell is in a patient. 5. The method of claim 1, wherein the cell is a bacterial cell, wherein the cell is in a patient. 6. The method of claim 1, wherein, when the compound is bound to a guanine-responsive riboswitch, R3 serves as a hydrogen bond acceptor and R2 serves as a hydrogen bond donor. 7. The method of claim 1, wherein R2, is C—NH2 or C—NH—CH3. 8. The method of claim 1, wherein R2, is C—NH2. 9. The method of claim 1, wherein R2, is C, N, O, or S substituted with a group that serves as a hydrogen bond donor. 10. The method of claim 1, wherein R2, is C substituted with a group that serves as a hydrogen bond donor. 11. The method of claim 1, wherein R10 is H, H2 or is not present. 12. The method of claim 1, wherein R2 is C═O. 13. The method of claim 1, wherein the riboswitch is a naturally occurring riboswitch, wherein the gene is a naturally occurring gene, and wherein the gene and riboswitch are not heterologous. 14. The method of claim 1, wherein the gene is essential to survival of the cell. 15. The method of claim 1, wherein the riboswitch comprises an aptamer domain and an expression platform domain, wherein the aptamer domain and the expression platform domain are heterologous. 16. The method of claim 1, wherein the riboswitch comprises an aptamer domain and an expression platform domain, wherein the aptamer domain comprises a P1 stem, wherein the P1 stem comprises an aptamer strand and a control strand, wherein the expression platform domain comprises a regulated strand, wherein the regulated strand, the control strand, or both have been designed to form a stem structure.
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Tkachuk Zenovy (Kiev SUX) Kvasyuk Eugeny (Kiev SUX) Matsuka Gennady (Kiev SUX) Mikhailopulo Igor (Kiev SUX), (2′-5′) oligoadenylate analogues useful as inhibitors of host-v5.-graft response.
Huynh Dinh Tam (Croissy/Seine FRX) Gouyette Catherine (Vanves FRX) Igolen Jean (Le Mesnil St. Denis FRX), 2,N6-disubstituted and 2,N6-trisubstituted adenosine-3′-phosphoramidites.
Suhadolnik Robert J. (Roslyn PA) Pfleiderer Wolfgang (Constance DEX), 2′,5′-phosphorothioate oligoadenylates and their covalent conjugates with polylysine.
Cook Philip D. (Carlsbad CA) Delecki Daniel J. (Radnor PA) Guinosso Charles (Vista CA), Acyclic nucleoside analogs and oligonucleotide sequences containing them.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
Cook Phillip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA) Vasseur Jean J. (San Marcos CA) Debart Francoise (Montpellier FRX), Backbone modified oligonucleotide analogues.
Sanghvi Yogesh S. (San Marcos CA) Cook Phillip D. (Vista CA), Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Ramsay Shaw Barbara (Durham NC), Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
Bertsch-Frank Birgit (Rheinfelden DEX) Klasen Claas-Juergen (Freigericht DEX) Lieser Thomas (Hapau DEX) Mueller Klaus (Hasselroth DEX) Bewersdorf Martin (Gelnhausen DEX), Coated sodium percarbonate particles, a process for their production and detergent, cleaning and bleaching compositions.
Whiteley Norman M. (San Carlos CA) Hunkapiller Michael W. (San Carlos CA) Glazer Alexander N. (Orinda CA), Detection of specific sequences in nucleic acids.
Baxter Anthony D. (Northwich GB2) Baylis Eric K. (Stockport GB2) Collingwood Stephen P. (Westhoughton GB2) Taylor Roger J. (Stretford GB2) De Mesmaeker Alain (Kanerkinden CHX) Schmit Chantal (Basel C, Dinucleoside phosphinates and their pharmaceutical compositions.
Froehler Brian (Belmont CA) Matteucci Mark (Burlingame CA), Enhanced triple-helix and double-helix formation with oligomers containing modified purines.
Sutherland John W. H. (Rochester NY) Patterson David R. (Rochester NY), Homogeneous method for assay of double-stranded nucleic acids using fluorescent dyes and kit useful therein.
Rogers Thomas E. (Manchester MO) Gray Steven H. (Ellisville MO) Devadas Balekudru (Chesterfield MO) Adams Steven P. (St. Charles MO), Improved probes using nucleosides containing 3-dezauracil analogs.
Morgan Jeffrey R. (Brighton MA) Mulligan Richard C. (Cambridge MA), In vivo introduction and expression of foreign genetic material in epithelial cells.
Noonberg Sarah B. (Berkeley CA) Hunt C. Anthony (San Francisco CA), In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides deriv.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke Shee L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Benner Steven A. (Hadlaubstrasse 151 CH-8006 Zurich CHX), Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases.
Matteucci Mark (Burlingame CA) Jones Robert J. (Daly City CA) Munger John (San Francisco CA), Modified internucleoside linkages having one nitrogen and two carbon atoms.
Ts\o Paul O. P. (2117 Folkstone Rd. Lutherville MD 21093) Miller Paul S. (225 Hopkins Rd. Baltimore MD 21212), Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof.
Cook Philip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA), Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression.
Meyer ; Jr. Rich B. (Woodinville WA) Adams A. David (Snohomish WA) Petrie Charles R. (Woodinville WA), Oligo (aa
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Letsinger Robert L. (Wilmette IL) Gryaznov Sergei M. (San Mateo CA), Oligodeoxyribonucleotides including 3′-aminonucleoside-phosphoramidate linkages and terminal 3′-amino groups.
Bischofberger Norbert (San Carlos CA) Kent Ken (Mountain View CA) Wagner Rick (Burlingame CA) Buhr Chris (Daly City CA) Lin Kuei-Ying (Fremont CA), Oligonucleotide analogs capable of passive cell membrane permeation.
Weis Alexander Ludvik (Berwyn PA) Hausheer Frederick Herman (San Antonio TX) Chaturvedula Prasad Venkata Chala (Exton PA) Delecki Daniel Joseph (Radnor PA) Cavanaugh ; Jr. Paul Francis (West Chester , Oligonucleotide analogues containing phosphate diester linkage substitutes, compositions thereof, and precursor dinucleo.
Smith Lloyd M. (South Pasadena CA) Fung Steven (Palo Alto CA) Kaiser ; Jr. Robert J. (Glendale CA), Oligonucleotides possessing a primary amino group in the terminal nucleotide.
Lebleu Bernard (Montpellier FRX) Bayard Bernard (Castelnau Le Lez FRX), Oligonucleotides with modified phosphate and modified carbohydrate moieties at the respective chain termini.
Imbach Jean-Louis (Montpellier FRX) Gosselin Gilles J. M. (Montpellier FRX), Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Shaw Barbara R. (Durham NC), Oligoribonucleoside and oligodeoxyribonucleoside boranophosphates.
Misiura Konrad (Lodz PLX) Gait Michael (Cambridge GB3), Phosphoramidite derivatives, their preparation and the use thereof in the incorporation of reporter groups on synthetic.
Maddry Joseph A. (Birmingham AL) Reynolds Robert C. (Birmingham AL) Secrist John A. (Birmingham AL) Montgomery John A. (Birmingham AL) Crooks Peter A. (Lexington KY), Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages.
Caruthers Marvin H. (Boulder CO) Marshall William S. (Boulder CO) Brill Wolfgang (Freiburg DEX) Nielsen John (Horsholm DKX), Polynucleotide phosphorodithioate.
Urdea Michael S. (Alamo CA) Horn Thomas (Berkeley CA), Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use.
Mullis Kary B. (La Jolla CA) Erlich Henry A. (Oakland CA) Arnheim Norman (Woodland Hills CA) Horn Glenn T. (Emeryville CA) Saiki Randall K. (Richmond CA) Scharf Stephen J. (Berkeley CA), Process for amplifying, detecting, and/or cloning nucleic acid sequences.
Mullis Kary B. (Kensington CA) Erlich Henry A. (Oakland CA) Arnheim Norman (Woodland Hills CA) Horn Glenn T. (Emeryville CA) Saiki Randall K. (Richmond CA) Scharf Stephen J. (Berkeley CA), Process for amplifying, detecting, and/or-cloning nucleic acid sequences.
Hawkins Mary E. (Potomac MD) Pfleiderer Wolfgang (Konstanz MD DEX) Davis Michael D. (Rockville MD) Balis Frank (Bethesda MD), Pteridine nucleotide analogs as fluorescent DNA probes.
Cech Thomas R. (573 Aztec Dr. Boulder CO 80303) Zaug Arthur J. (623 W. Lilac Ct. Louisville CO 80027) Been Michael D. (705 Aurora Ave. ; Apt. 4 Boulder CO 80303), RNA Ribozyme which cleaves substrate RNA without formation of a convalent bond.
Cech Thomas R. (Boulder CO) Zaug Arthur J. (Louisville CO) Been Michael D. (Boulder CO), RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods.
Van Ness Jeffrey (Bothell WA) Petrie Charles R. (Woodinville WA) Tabone John C. (Bothell WA) Vermeulen Nicolaas M. J. (Woodinville WA), Solid supports for nucleic acid hybridization assays.
Fraiser Melinda S. (Durham NC) Spargo Catherine A. (Cary NC) Walker George Terrance (Chapel Hill NC) Van Cleve Mark (San Jose CA) Wright David James (Chapel Hill NC) Little Michael C. (Baltimore MD), Strand displacement amplification using thermophilic enzymes.
Fraiser Melinda S. ; Spargo Catherine A. ; Walker George Terrance ; Van Cleve Mark ; Wright David James ; Little Michael C., Strand displacement amplification using thermophilic enzymes.
Cook Phillip Dan (Carlsbad CA) Manoharan Muthiah (Carlsbad CA) Ramasamy Kanda S. (Laguna Hills CA), Substituted purines and oligonucleotide cross-linking.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR), Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages.
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