HRP20220607T1 - Terminalno modificirana rna - Google Patents
Terminalno modificirana rna Download PDFInfo
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- HRP20220607T1 HRP20220607T1 HRP20220607TT HRP20220607T HRP20220607T1 HR P20220607 T1 HRP20220607 T1 HR P20220607T1 HR P20220607T T HRP20220607T T HR P20220607TT HR P20220607 T HRP20220607 T HR P20220607T HR P20220607 T1 HRP20220607 T1 HR P20220607T1
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- Croatia
- Prior art keywords
- formulation
- nanoparticles according
- lipid nanoparticles
- mrna
- microrna
- Prior art date
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- 238000009472 formulation Methods 0.000 claims 16
- 150000002632 lipids Chemical class 0.000 claims 16
- 239000000203 mixture Substances 0.000 claims 16
- 239000002105 nanoparticle Substances 0.000 claims 16
- 108700011259 MicroRNAs Proteins 0.000 claims 10
- 108020004999 messenger RNA Proteins 0.000 claims 10
- 239000002679 microRNA Substances 0.000 claims 10
- 239000002777 nucleoside Substances 0.000 claims 7
- 108020003589 5' Untranslated Regions Proteins 0.000 claims 5
- 125000003835 nucleoside group Chemical group 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 3
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 108091079658 miR-142-1 stem-loop Proteins 0.000 claims 3
- 108091071830 miR-142-2 stem-loop Proteins 0.000 claims 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 3
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims 2
- 210000002865 immune cell Anatomy 0.000 claims 2
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 claims 2
- QOXJRLADYHZRGC-SHYZEUOFSA-N 1-[(2r,3r,5s)-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O1[C@H](CO)C[C@@H](O)[C@@H]1N1C(=O)NC(=O)C=C1 QOXJRLADYHZRGC-SHYZEUOFSA-N 0.000 claims 1
- UTAIYTHAJQNQDW-KQYNXXCUSA-N 1-methylguanosine Chemical compound C1=NC=2C(=O)N(C)C(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O UTAIYTHAJQNQDW-KQYNXXCUSA-N 0.000 claims 1
- UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical group O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 claims 1
- UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 claims 1
- WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 claims 1
- BTOTXLJHDSNXMW-POYBYMJQSA-N 2,3-dideoxyuridine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(=O)NC(=O)C=C1 BTOTXLJHDSNXMW-POYBYMJQSA-N 0.000 claims 1
- OFEZSBMBBKLLBJ-UHFFFAOYSA-N 2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1OC(CO)CC1O OFEZSBMBBKLLBJ-UHFFFAOYSA-N 0.000 claims 1
- JRYMOPZHXMVHTA-DAGMQNCNSA-N 2-amino-7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1h-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=CC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O JRYMOPZHXMVHTA-DAGMQNCNSA-N 0.000 claims 1
- BGTXMQUSDNMLDW-AEHJODJJSA-N 2-amino-9-[(2r,3s,4r,5r)-3-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@]1(O)F BGTXMQUSDNMLDW-AEHJODJJSA-N 0.000 claims 1
- OCLZPNCLRLDXJC-NTSWFWBYSA-N 2-amino-9-[(2r,5s)-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](CO)O1 OCLZPNCLRLDXJC-NTSWFWBYSA-N 0.000 claims 1
- -1 3'-deoxycytosine Chemical compound 0.000 claims 1
- OROIAVZITJBGSM-OBXARNEKSA-N 3'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)C[C@H]1O OROIAVZITJBGSM-OBXARNEKSA-N 0.000 claims 1
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 claims 1
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 claims 1
- HCAJQHYUCKICQH-VPENINKCSA-N 8-Oxo-7,8-dihydro-2'-deoxyguanosine Chemical compound C1=2NC(N)=NC(=O)C=2NC(=O)N1[C@H]1C[C@H](O)[C@@H](CO)O1 HCAJQHYUCKICQH-VPENINKCSA-N 0.000 claims 1
- 241000180579 Arca Species 0.000 claims 1
- 101150077194 CAP1 gene Proteins 0.000 claims 1
- 101150014715 CAP2 gene Proteins 0.000 claims 1
- 101710180456 CD-NTase-associated protein 4 Proteins 0.000 claims 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 1
- 229930010555 Inosine Natural products 0.000 claims 1
- 108091007780 MiR-122 Proteins 0.000 claims 1
- 101100245221 Mus musculus Prss8 gene Proteins 0.000 claims 1
- 101100260872 Mus musculus Tmprss4 gene Proteins 0.000 claims 1
- 229930185560 Pseudouridine Natural products 0.000 claims 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 claims 1
- 108091036066 Three prime untranslated region Proteins 0.000 claims 1
- 108091023045 Untranslated Region Proteins 0.000 claims 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 claims 1
- 230000015556 catabolic process Effects 0.000 claims 1
- 238000006731 degradation reaction Methods 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 229940029575 guanosine Drugs 0.000 claims 1
- 229960003786 inosine Drugs 0.000 claims 1
- 108091051828 miR-122 stem-loop Proteins 0.000 claims 1
- 108091032320 miR-146 stem-loop Proteins 0.000 claims 1
- 108091024530 miR-146a stem-loop Proteins 0.000 claims 1
- 108091043612 miR-146b stem-loop Proteins 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000014621 translational initiation Effects 0.000 claims 1
- 229940035893 uracil Drugs 0.000 claims 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 1
- 229940045145 uridine Drugs 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/67—General methods for enhancing the expression
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Saccharide Compounds (AREA)
Claims (16)
1. Formulacija lipidnih nanočestica mRNA za ciljanu ekspresiju polipeptida od interesa u specifičnim tipovima stanica, navedena mRNA koja sadrži
(a) neprevedeno područje 5’
(b) regija povezanih nukleozida koja kodira polipeptid od interesa;
(c) neprevedeno područje 3' koje sadrži najmanje jedno vezno mjesto mikroRNA za mikroRNA izraženu u specifičnom tipu stanice tako da se ekspresija mRNA može smanjiti, pri čemu je mRNA usmjerena na razgradnju ili smanjenu translaciju u prisutnosti mikroRNA; i
(d) repno područje 3' povezanih nukleozida,
pri čemu je uracil ili uridin u mRNA zamijenjen do 100% modificiranim uracilom ili modificiranim uridinom, odnosno.
2. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što bilo koja od regija (a) - (d) u zahtjevu 1 sadrži najmanje jedan analog pseudouridina,
pri čemu je izborno analog pseudouridina 1-metilpseudouridin u kojem slučaju mRNA izborno dodatno sadrži modificirani nukleozid 5-metilcitidin.
3. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što je barem jedno područje mRNA optimizirano kodonom, izborno pri čemu je područje povezanih nukleozida koji kodiraju navedeni polipeptid od interesa optimiziran za kodon.
4. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što je 5' UTR nativni 5'UTR kodiranog polipeptida.
5. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što 5'UTR sadrži sekvencu inicijacije translacije odabranu iz skupine koja se sastoji od Kozakove sekvence i unutarnjeg ulaznog mjesta ribosoma (IRES).
6. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što je 5'UTR strukturirani UTR.
7. Formulacija lipidnih nanočestica prema zahtjevu 1, koja sadrži najmanje jednu strukturu kape 5', naznačena time što je izborno najmanje jedna struktura kape 5' odabrana iz skupine koja se sastoji od Cap0, Cap1, ARCA, inozin, N1-metil-gvanozin, 2'fluor-gvanozin, 7-deaza-gvanozin, 8-okso-gvanozin, 2-amino-gvanozin, LNA- gvanozin, 2-azido-gvanozin, Cap2, Cap4, i CAP-003 - CAP-225.
8. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što je najmanje jedno vezno mjesto mikroRNA za specifičnu imunološku stanicu mikroRNA,
pri čemu je izborno specifična imunološka stanica mikroRNA odabrana iz skupine koja se sastoji od miR-122, miR-142-3p, miR-142-5p, miR-146a i miR-146b.
9. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što repno područje 3' povezanih nukleozida nadalje sadrži nukleozid završnog lanca,
pri čemu je izborno nukleozid završnog lanca odabran iz skupine koja se sastoji od 3'-deoksiadenozina (kordicepin), 3'-deoksiuridina, 3'-deoksicitozina, 3'-deoksigvanozina, 3'-deoksitimina, 2',3'-dideoksinukleozida, 2',3'-dideoksiadenozina, 2',3'-dideoksiuridina, 2',3'-dideoksicitozina, 2',3'-dideoksiguanozina, 2',3'-dideoksitimina, 2'-deoksinukleozida i -O-metilnukleozida.
10. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što repno područje 3' sadrži sekvencu petlje stabljike.
11. Formulacija lipidnih nanočestica prema zahtjevu 1, naznačena time što 5'UTR sadrži najmanje jednu sekvencu elementa za pojačavanje translacije (TEE).
12. Formulacija lipidnih nanočestica prema bilo kojem od prethodnih zahtjeva, naznačena time što je najmanje jedno vezno mjesto mikroRNA za miR-142-3p.
13. Formulacija lipidnih nanočestica prema bilo kojem od prethodnih zahtjeva, naznačena time što mRNA sadrži najmanje dva vezna mjesta mikroRNA.
14. Formulacija lipidnih nanočestica prema zahtjevu 13, naznačena time što su vezna mjesta mikroRNA ista.
15. Formulacija lipidnih nanočestica prema zahtjevu 13, naznačena time što su vezna mjesta mikroRNA različita.
16. Formulacija lipidnih nanočestica mRNA kako je definirana u bilo kojem od zahtjeva 1-15 za uporabu u terapijskoj metodi gdje je ekspresija mRNA usmjerena na specifične tipove stanica.
Applications Claiming Priority (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261729933P | 2012-11-26 | 2012-11-26 | |
US201261737224P | 2012-12-14 | 2012-12-14 | |
US201361758921P | 2013-01-31 | 2013-01-31 | |
US201361775509P | 2013-03-09 | 2013-03-09 | |
US201361781139P | 2013-03-14 | 2013-03-14 | |
US201361829372P | 2013-05-31 | 2013-05-31 | |
US201361829359P | 2013-05-31 | 2013-05-31 | |
US201361839903P | 2013-06-27 | 2013-06-27 | |
US201361842709P | 2013-07-03 | 2013-07-03 | |
US201361857436P | 2013-07-23 | 2013-07-23 | |
EP13779667.8A EP2922554B1 (en) | 2012-11-26 | 2013-10-02 | Terminally modified rna |
PCT/US2013/062943 WO2014081507A1 (en) | 2012-11-26 | 2013-10-02 | Terminally modified rna |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20220607T1 true HRP20220607T1 (hr) | 2022-06-24 |
Family
ID=49447811
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20220607TT HRP20220607T1 (hr) | 2012-11-26 | 2013-10-02 | Terminalno modificirana rna |
Country Status (15)
Country | Link |
---|---|
US (3) | US9597380B2 (hr) |
EP (2) | EP4074834A1 (hr) |
JP (5) | JP6144355B2 (hr) |
AU (3) | AU2017202228B2 (hr) |
CA (1) | CA2892529C (hr) |
DK (1) | DK2922554T3 (hr) |
ES (1) | ES2921623T3 (hr) |
HK (1) | HK1214515A1 (hr) |
HR (1) | HRP20220607T1 (hr) |
LT (1) | LT2922554T (hr) |
PL (1) | PL2922554T3 (hr) |
PT (1) | PT2922554T (hr) |
RS (1) | RS63237B1 (hr) |
SI (1) | SI2922554T1 (hr) |
WO (1) | WO2014081507A1 (hr) |
Families Citing this family (260)
Publication number | Priority date | Publication date | Assignee | Title |
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DE10347710B4 (de) | 2003-10-14 | 2006-03-30 | Johannes-Gutenberg-Universität Mainz | Rekombinante Impfstoffe und deren Verwendung |
DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
DK3338765T3 (en) | 2009-12-01 | 2019-03-04 | Translate Bio Inc | STEROID DERIVATIVE FOR THE SUPPLY OF MRNA IN HUMANGENETIC DISEASES |
ES2770335T3 (es) | 2010-07-06 | 2020-07-01 | Glaxosmithkline Biologicals Sa | Administración de ARN para desencadenar múltiples vías inmunológicas |
BR112013000244A2 (pt) | 2010-07-06 | 2016-05-17 | Novartis Ag | lipossomas com lipídeos apresentando pka vantajoso para administração de rna |
EP2591114B1 (en) | 2010-07-06 | 2016-06-08 | GlaxoSmithKline Biologicals SA | Immunisation of large mammals with low doses of rna |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
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AU2011295935B2 (en) | 2010-08-31 | 2016-02-11 | Glaxosmithkline Biologicals S.A. | Pegylated liposomes for delivery of immunogen-encoding RNA |
CN104531812A (zh) | 2010-10-01 | 2015-04-22 | 现代治疗公司 | 设计核酸及其使用方法 |
KR102266691B1 (ko) | 2010-10-11 | 2021-06-23 | 노파르티스 아게 | 항원 전달 플랫폼 |
WO2012075040A2 (en) | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
JP2014511687A (ja) | 2011-03-31 | 2014-05-19 | モデルナ セラピューティクス インコーポレイテッド | 工学操作された核酸の送達および製剤 |
US10738355B2 (en) | 2011-05-24 | 2020-08-11 | Tron-Translationale Onkologie An Der Universitätsmedizin Der Johannes Gutenberg-Universität Mainz Ggmbh | Individualized vaccines for cancer |
PL2717893T3 (pl) | 2011-06-08 | 2019-12-31 | Translate Bio, Inc. | Kompozycje nanocząstek lipidowych i sposoby do dostarczania mRNA |
JP2014522842A (ja) | 2011-07-06 | 2014-09-08 | ノバルティス アーゲー | 免疫原性組み合わせ組成物およびその使用 |
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ES2911677T3 (es) | 2011-10-03 | 2022-05-20 | Modernatx Inc | Nucleósidos, nucleótidos y ácidos nucleicos modificados, y sus usos |
RS63244B1 (sr) | 2011-12-16 | 2022-06-30 | Modernatx Inc | Kompozicije modifikovane mrna |
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WO2013120498A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded allergenic antigen or an autoimmune self-antigen |
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