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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0266791 (2016-09-15) |
등록번호 | US-10022425 (2018-07-17) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 379 |
Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to kill or reduce the growth of microorganisms. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent microbial infection, or to i
Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to kill or reduce the growth of microorganisms. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent microbial infection, or to improve a subject's heath or wellbeing.
1. A method of treating a microbial infection, comprising administering to a subject a pharmaceutical composition comprising a lipid-based nanoparticle comprising a synthetic messenger ribonucleic acid (mRNA) encoding a defensin polypeptide in an amount effective to permit production of the defensin
1. A method of treating a microbial infection, comprising administering to a subject a pharmaceutical composition comprising a lipid-based nanoparticle comprising a synthetic messenger ribonucleic acid (mRNA) encoding a defensin polypeptide in an amount effective to permit production of the defensin polypeptide in a cell, wherein the synthetic mRNA comprises a translatable region that contains at least one nucleoside modification, and wherein 75-100% of uridine nucleotides in the synthetic mRNA are modified. 2. The method of claim 1, wherein the subject is human. 3. The method of claim 1, wherein the subject is a livestock animal. 4. The method of claim 1, wherein the pharmaceutical composition is administered by a route selected from the group consisting of systemic, local, intravenous, topical, oral, administration via a dressing, administration via a bandage, rectal, vaginal, intramuscular, transarterial, intraperitoneal, intranasally, subcutaneously, endoscopically, transdermally and intrathecally. 5. The method of claim 4, wherein the route is intravenous. 6. The method of claim 4, wherein the administration is repeated at least once. 7. The method of claim 1, further comprising administering an effective amount of a small molecule anti-microbial compound to the subject at the same time or at a different time from the administration of the pharmaceutical composition. 8. The method of claim 1, wherein the at least one nucleoside modification is selected from the group consisting of pyridin-4-one ribonucleoside, 5-aza-uridine, 2-thio-5-aza-uridine, 2-thiouridine, 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxyuridine, 3-methyluridine, 5-carboxymethyl-uridine, 1-carboxymethyl-pseudouridine, 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyluridine, 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine, 1-taurinomethyl-4-thio-uridine, 5-methyl-uridine, 1-methyl-pseudouridine, 4-thio-1-methyl-pseudouridine, 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine, dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, 5-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine, N4-acetylcytidine, 5-formylcytidine, N4-methylcytidine, 5-hydroxymethylcytidine, 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine, 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deaza-pseudoisocytidine, 1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine, 2-aminopurine, 2, 6-diaminopurine, 7-deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-aminopurine, 7-deaza-8-aza-2-aminopurine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyladenosine, N6-methyladenosine, N6-isopentenyladenosine, N6-(cis-hydroxyisopentenyl)adenosine, 2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine, N6-glycinylcarbamoyladenosine, N6-threonylcarbamoyladeno sine, 2-methylthio-N6-threonyl carbamoyladenosine, N6,N6-dimethyladenosine, 7-methyladenine, 2-methylthio-adenine, 2-methoxy-adenine, inosine, 1-methyl-inosine, wyosine, wybuto sine, 7-deaza-guanosine, 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine, 6-thio-7-methyl-guanosine, 7-methylinosine, 6-methoxy-guanosine, 1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, and N2,N2-dimethyl-6-thio-guanosine. 9. The method of claim 1, wherein the defensin polypeptide is selected from the group consisting of α-defensins, β-defensins, and θ-defensins. 10. The method of claim 1, wherein the defensin polypeptide is human beta-defensin-2 (hBD-2) (SEQ ID NO: 191 or 192). 11. The method of claim 9, wherein the defensin polypeptide is an α-defensin polypeptide selected from the group consisting of neutrophil defensin 1, defensin alpha 1, neutrophil defensin 3, neutrophil defensin 4, defensin 5, and defensin 6. 12. The method of claim 9, wherein the defensin polypeptide is a β-defensin polypeptide selected from the group consisting of beta-defensin 1, beta-defensin 2, beta-defensin 103, beta-defensin 107, beta-defensin 110, and beta-defensin 136. 13. The method of claim 9, wherein the at least one nucleoside modification is pseudouridine. 14. The method of claim 9, wherein 100% of uridine nucleotides in the synthetic mRNA are modified. 15. The method of claim 9, wherein the synthetic mRNA further comprises a 5′ untranslated region that contains at least one nucleoside modification. 16. The method of claim 15, wherein the synthetic mRNA further comprises a 5′ untranslated region that contains at least two nucleoside modifications. 17. The method of claim 9, wherein the synthetic mRNA further comprises a 3′ untranslated region that contains at least one nucleoside modification. 18. The method of claim 17, wherein the synthetic mRNA further comprises a 3′ untranslated region that contains at least two nucleoside modifications. 19. A method of treating a microbial infection, comprising administering to a subject a lipid-based nanoparticle comprising a synthetic messenger ribonucleic acid (mRNA) encoding a defensin polypeptide in an amount effective to permit production of the defensin polypeptide in a cell, wherein 75-100% of uridine nucleotides in the synthetic mRNA are modified, andwherein the synthetic mRNA comprises a translatable region, a 5′ untranslated region and a 3′ untranslated region, each of which contains at least one nucleoside modification. 20. The method of claim 19, wherein the subject is human. 21. The method of claim 19, wherein the defensin polypeptide is selected from the group consisting of α-defensins, β-defensins, and θ-defensins. 22. The method of claim 19, wherein the defensin polypeptide is human beta-defensin-2 (hBD-2) (SEQ ID NO: 191 or 192). 23. The method of claim 21, wherein the defensin polypeptide is an α-defensin polypeptide selected from the group consisting of neutrophil defensin 1, defensin alpha 1, neutrophil defensin 3, neutrophil defensin 4, defensin 5, and defensin 6. 24. The method of claim 21, wherein the defensin polypeptide is a β-defensin polypeptide selected from the group consisting of beta-defensin 1, beta-defensin 2, beta-defensin 103, beta-defensin 107, beta-defensin 110, and beta-defensin 136. 25. The method of claim 19, wherein the at least one nucleoside modification is pseudouridine.
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