EA201591281A1 - Рибонуклеиновые кислоты с 4'-тиомодифицированными нуклеотидами и связанные с ними способы - Google Patents

Рибонуклеиновые кислоты с 4'-тиомодифицированными нуклеотидами и связанные с ними способы

Info

Publication number
EA201591281A1
EA201591281A1 EA201591281A EA201591281A EA201591281A1 EA 201591281 A1 EA201591281 A1 EA 201591281A1 EA 201591281 A EA201591281 A EA 201591281A EA 201591281 A EA201591281 A EA 201591281A EA 201591281 A1 EA201591281 A1 EA 201591281A1
Authority
EA
Eurasian Patent Office
Prior art keywords
thiomodified
nucleotides
related methods
ribonucleic acids
mrna
Prior art date
Application number
EA201591281A
Other languages
English (en)
Inventor
Франк Дероза
Майкл Хартлейн
Original Assignee
Шир Хьюман Дженетик Терапис, Инк.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Шир Хьюман Дженетик Терапис, Инк. filed Critical Шир Хьюман Дженетик Терапис, Инк.
Publication of EA201591281A1 publication Critical patent/EA201591281A1/ru

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)

Abstract

Раскрыты молекулы матричных РНК и связанные с ними композиции, содержащие 4'-тиомодификацию в фуранозном кольце по меньшей мере одного нуклеотидного остатка, и способы использования таких мРНК для продуцирования кодируемого терапевтического белка in vivo и для лечения или профилактики болезней или расстройств. В определенных вариантах реализации изобретения 4'-тиомодифицированная мРНК обеспечивает повышенную стабильность и/или пониженную иммуногенность in vivo терапии.
EA201591281A 2013-03-14 2014-03-14 Рибонуклеиновые кислоты с 4'-тиомодифицированными нуклеотидами и связанные с ними способы EA201591281A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361785098P 2013-03-14 2013-03-14
PCT/US2014/027422 WO2014152513A1 (en) 2013-03-14 2014-03-14 RIBONUCLEIC ACIDs WITH 4'-THIO-MODIFIED NUCLEOTIDES AND RELATED METHODS

Publications (1)

Publication Number Publication Date
EA201591281A1 true EA201591281A1 (ru) 2016-02-29

Family

ID=50639964

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201591281A EA201591281A1 (ru) 2013-03-14 2014-03-14 Рибонуклеиновые кислоты с 4'-тиомодифицированными нуклеотидами и связанные с ними способы

Country Status (16)

Country Link
US (4) US10266559B2 (ru)
EP (3) EP2970351B1 (ru)
JP (1) JP6567494B2 (ru)
KR (1) KR20150127582A (ru)
CN (1) CN105026411A (ru)
AU (2) AU2014239562B2 (ru)
BR (1) BR112015022507A2 (ru)
CA (1) CA2902884C (ru)
EA (1) EA201591281A1 (ru)
ES (2) ES2797974T3 (ru)
HK (1) HK1219955A1 (ru)
IL (1) IL240465A0 (ru)
MX (1) MX2015011943A (ru)
SG (1) SG11201507474QA (ru)
WO (1) WO2014152513A1 (ru)
ZA (1) ZA201507605B (ru)

Families Citing this family (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR201901311T4 (tr) 2009-12-01 2019-02-21 Translate Bio Inc İnsan genetik hastalıklarında mRNA'nın teslimi için steroid türevi.
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
EP4212514A1 (en) 2011-06-08 2023-07-19 Translate Bio, Inc. Cleavable lipids
BR112013031553A2 (pt) 2011-06-08 2020-11-10 Shire Human Genetic Therapies, Inc. composições, mrna que codifica para uma hgla e seu uso, uso de pelo menos uma molécula de mrna e um veículo de transferência e uso de um mrna que codifica para proteína exógena
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
EP2834358A4 (en) 2012-04-02 2016-03-09 Moderna Therapeutics Inc MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF NUCLEAR PROTEINS
WO2013185067A1 (en) 2012-06-08 2013-12-12 Shire Human Genetic Therapies, Inc. Nuclease resistant polynucleotides and uses thereof
CN105142676B (zh) 2013-03-14 2022-06-28 夏尔人类遗传性治疗公司 Cftr mrna组合物以及相关方法和用途
SG11201507425RA (en) 2013-03-14 2015-10-29 Shire Human Genetic Therapies Methods for purification of messenger rna
US10138507B2 (en) 2013-03-15 2018-11-27 Modernatx, Inc. Manufacturing methods for production of RNA transcripts
US10077439B2 (en) 2013-03-15 2018-09-18 Modernatx, Inc. Removal of DNA fragments in mRNA production process
US10590161B2 (en) 2013-03-15 2020-03-17 Modernatx, Inc. Ion exchange purification of mRNA
US11377470B2 (en) 2013-03-15 2022-07-05 Modernatx, Inc. Ribonucleic acid purification
WO2014197578A1 (en) * 2013-06-05 2014-12-11 Idenix Pharmaceuticals, Inc. 1',4'-thio nucleosides for the treatment of hcv
EP3019619B1 (en) 2013-07-11 2021-08-25 ModernaTX, Inc. Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use
WO2015051169A2 (en) 2013-10-02 2015-04-09 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
EP3052521A1 (en) 2013-10-03 2016-08-10 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor
EP3501605B1 (en) 2013-10-22 2023-06-28 Translate Bio, Inc. Mrna therapy for argininosuccinate synthetase deficiency
EP3060258A1 (en) 2013-10-22 2016-08-31 Shire Human Genetic Therapies, Inc. Mrna therapy for phenylketonuria
JP6571679B2 (ja) 2014-04-25 2019-09-04 トランスレイト バイオ， インコーポレイテッド メッセンジャーｒｎａの精製方法
EP3157573A4 (en) 2014-06-19 2018-02-21 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
AU2015289656A1 (en) 2014-07-16 2017-02-16 Modernatx, Inc. Circular polynucleotides
GB201508025D0 (en) 2015-05-11 2015-06-24 Ucl Business Plc Fabry disease gene therapy
US11434486B2 (en) 2015-09-17 2022-09-06 Modernatx, Inc. Polynucleotides containing a morpholino linker
CA2998370A1 (en) 2015-09-17 2017-03-23 Moderna Therapeutics, Inc. Polynucleotides containing a stabilizing tail region
JP7065036B2 (ja) 2015-12-17 2022-05-11 モダーナティエックス・インコーポレイテッド メチルマロニルＣｏＡムターゼをコードするポリヌクレオチド
WO2017127750A1 (en) 2016-01-22 2017-07-27 Modernatx, Inc. Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof
JP7150608B6 (ja) * 2016-04-08 2022-11-11 トランスレイト バイオ， インコーポレイテッド 多量体コード核酸及びその使用
WO2017180917A2 (en) 2016-04-13 2017-10-19 Modernatx, Inc. Lipid compositions and their uses for intratumoral polynucleotide delivery
AU2017266932B2 (en) 2016-05-18 2023-04-20 Modernatx, Inc. Polynucleotides encoding alpha-galactosidase A for the treatment of Fabry disease
MA45053A (fr) 2016-05-18 2019-03-27 Modernatx Inc Polynucléotides codant pour un régulateur de conductance transmembranaire de fibrose kystique pour le traitement de la fibrose kystique
JP7246930B2 (ja) 2016-05-18 2023-03-28 モデルナティエックス インコーポレイテッド インターロイキン－１２（ｉｌ１２）をコードするポリヌクレオチドおよびその使用
WO2018157141A1 (en) 2017-02-27 2018-08-30 Translate Bio, Inc. Methods for purification of messenger rna
US10808241B2 (en) 2017-02-27 2020-10-20 Translate Bio, Inc. Methods for purification of messenger RNA
AU2018224326B2 (en) 2017-02-27 2024-01-04 Translate Bio, Inc. Novel codon-optimized CFTR mRNA
EP3592728A1 (en) 2017-03-07 2020-01-15 Translate Bio, Inc. Polyanionic delivery of nucleic acids
MA49138A (fr) 2017-05-16 2020-03-25 Translate Bio Inc Traitement de la fibrose kystique par administration d'arnm à codons optimisés codant pour la cftr
JP7284101B2 (ja) 2017-05-31 2023-05-30 ウルトラジェニクス ファーマシューティカル インク． 糖原病ｉｉｉ型のための治療薬
EP4047039A1 (en) 2017-06-12 2022-08-24 Translate Bio, Inc. Poly(phosphoesters) for delivery of nucleic acids
US20200131498A1 (en) 2017-06-14 2020-04-30 Modernatx, Inc. Polynucleotides encoding methylmalonyl-coa mutase
US10780183B2 (en) 2017-06-19 2020-09-22 Translate Bio, Inc. Messenger RNA therapy for the treatment of Friedreich's ataxia
US11939601B2 (en) 2017-11-22 2024-03-26 Modernatx, Inc. Polynucleotides encoding phenylalanine hydroxylase for the treatment of phenylketonuria
US11859215B2 (en) 2017-11-22 2024-01-02 Modernatx, Inc. Polynucleotides encoding ornithine transcarbamylase for the treatment of urea cycle disorders
WO2019152802A1 (en) 2018-02-02 2019-08-08 Translate Bio, Inc. Cationic polymers
EP3793689A1 (en) * 2018-05-15 2021-03-24 Translate Bio, Inc. Subcutaneous delivery of messenger rna
EP3794008A1 (en) 2018-05-16 2021-03-24 Translate Bio, Inc. Ribose cationic lipids
US12076439B2 (en) 2018-05-24 2024-09-03 Translate Bio, Inc. Thioester cationic lipids
JP7441802B2 (ja) 2018-05-30 2024-03-01 トランスレイト バイオ， インコーポレイテッド ビタミンカチオン性脂質
US20200016274A1 (en) * 2018-05-30 2020-01-16 Translate Bio, Inc. Messenger rna vaccines and uses thereof
MA52762A (fr) 2018-05-30 2021-04-14 Translate Bio Inc Lipides cationiques comprenant une fraction stéroïdienne
WO2019232097A1 (en) 2018-05-30 2019-12-05 Translate Bio, Inc. Phosphoester cationic lipids
US20210378977A1 (en) * 2018-07-23 2021-12-09 Translate Bio, Inc. Dry Powder Formulations for Messenger RNA
CN112930396B (zh) 2018-08-24 2024-05-24 川斯勒佰尔公司 用于纯化信使rna的方法
CA3110914A1 (en) 2018-09-28 2020-04-02 Nutcracker Therapeutics, Inc. Tertiary amino lipidated cationic peptides for nucleic acid delivery
WO2020077007A1 (en) 2018-10-09 2020-04-16 The University Of British Columbia Compositions and systems comprising transfection-competent vesicles free of organic-solvents and detergents and methods related thereto
AU2019376004A1 (en) 2018-11-08 2021-05-13 Translate Bio, Inc. Methods and compositions for messenger RNA purification
US20220071905A1 (en) 2018-11-09 2022-03-10 Translate Bio, Inc. Peg lipidoid compounds
CA3117882A1 (en) 2018-11-09 2020-05-14 Translate Bio, Inc. 2,5-dioxopiperazine lipids with intercalated ester, thioester, disulfide and anhydride moieities
AU2019377525A1 (en) 2018-11-09 2021-05-27 Translate Bio, Inc. Multi-PEG lipid compounds
AU2019383413A1 (en) 2018-11-21 2021-05-27 Translate Bio, Inc. Cationic lipid compounds and compositions thereof for use in the delivery of messenger RNA
EP3956303A1 (en) 2019-04-18 2022-02-23 Translate Bio, Inc. Cystine cationic lipids
ES2972014T3 (es) 2019-04-22 2024-06-10 Translate Bio Inc Lípidos catiónicos de tioéster
WO2020227085A1 (en) 2019-05-03 2020-11-12 Translate Bio, Inc. Di-thioester cationic lipids
EP3976593A1 (en) 2019-05-31 2022-04-06 Translate Bio, Inc. Macrocyclic lipids
CN117945938A (zh) 2019-06-21 2024-04-30 川斯勒佰尔公司 三(羟甲基)甲基甘氨酸和柠檬酸脂质
WO2020257611A1 (en) 2019-06-21 2020-12-24 Translate Bio, Inc. Cationic lipids comprising an hydroxy moiety
CN111041025B (zh) 2019-12-17 2021-06-18 深圳市瑞吉生物科技有限公司 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法
WO2021202788A2 (en) * 2020-04-03 2021-10-07 Ionis Pharmaceuticals, Inc. Modified oligomeric compounds and uses thereof
EP4149556A1 (en) 2020-05-14 2023-03-22 Translate Bio, Inc. Peg lipidoid compounds
CN111744019B (zh) 2020-07-01 2023-08-04 深圳瑞吉生物科技有限公司 基于甘露糖的mRNA靶向递送系统及其应用
CN114736260B (zh) * 2022-03-29 2024-08-23 上海吉量医药工程有限公司 一种三磷酸核苷酸盐的制备方法
KR20230170587A (ko) * 2022-06-10 2023-12-19 주식회사 피노바이오 4'-티오-5-아자-2'-데옥시사이티딘의 제조방법

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ210501A (en) * 1983-12-13 1991-08-27 Kirin Amgen Inc Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
EP1677822B1 (en) * 2003-09-18 2014-04-23 Isis Pharmaceuticals, Inc. 4'-thionucleosides and oligomeric compounds
US20100015218A1 (en) * 2007-02-16 2010-01-21 Vasant Jadhav Compositions and methods for potentiated activity of biologically active molecules
KR101734955B1 (ko) 2008-11-07 2017-05-12 메사추세츠 인스티튜트 오브 테크놀로지 아미노알콜 리피도이드 및 그의 용도
DE102009032885A1 (de) 2009-07-13 2011-02-03 Siemens Aktiengesellschaft Ringförmiger Rotor für eine elektrische Maschine
TR201901311T4 (tr) * 2009-12-01 2019-02-21 Translate Bio Inc İnsan genetik hastalıklarında mRNA'nın teslimi için steroid türevi.
BR112013031553A2 (pt) 2011-06-08 2020-11-10 Shire Human Genetic Therapies, Inc. composições, mrna que codifica para uma hgla e seu uso, uso de pelo menos uma molécula de mrna e um veículo de transferência e uso de um mrna que codifica para proteína exógena
EP4212514A1 (en) 2011-06-08 2023-07-19 Translate Bio, Inc. Cleavable lipids
PT3682905T (pt) 2011-10-03 2022-04-07 Modernatx Inc Nucleósidos, nucleótidos e ácidos nucleicos modificados e respetivas utilizações
WO2015051173A2 (en) 2013-10-02 2015-04-09 Moderna Therapeutics, Inc Polynucleotide molecules and uses thereof
WO2015051169A2 (en) 2013-10-02 2015-04-09 Moderna Therapeutics, Inc. Polynucleotide molecules and uses thereof
US20150167017A1 (en) 2013-12-13 2015-06-18 Moderna Therapeutics, Inc. Alternative nucleic acid molecules and uses thereof
WO2016164762A1 (en) 2015-04-08 2016-10-13 Moderna Therapeutics, Inc. Polynucleotides encoding low density lipoprotein receptor egf-a and intracellular domain mutants and methods of using the same

Also Published As

Publication number Publication date
IL240465A0 (en) 2015-09-24
US20190263850A1 (en) 2019-08-29
WO2014152513A1 (en) 2014-09-25
EP2970351A1 (en) 2016-01-20
CA2902884C (en) 2021-05-25
AU2018203985A1 (en) 2018-06-21
HK1219955A1 (zh) 2017-04-21
KR20150127582A (ko) 2015-11-17
EP3750903A1 (en) 2020-12-16
CA2902884A1 (en) 2014-09-25
SG11201507474QA (en) 2015-10-29
AU2014239562B2 (en) 2018-07-05
US20230192753A1 (en) 2023-06-22
US20210009629A1 (en) 2021-01-14
ES2797974T3 (es) 2020-12-04
ES2647832T3 (es) 2017-12-26
CN105026411A (zh) 2015-11-04
US10822368B2 (en) 2020-11-03
EP3301102B1 (en) 2020-04-15
EP3301102A1 (en) 2018-04-04
US11447520B2 (en) 2022-09-20
BR112015022507A2 (pt) 2017-10-24
JP2016513470A (ja) 2016-05-16
US20160031928A1 (en) 2016-02-04
ZA201507605B (en) 2017-01-25
MX2015011943A (es) 2015-12-01
JP6567494B2 (ja) 2019-08-28
EP2970351B1 (en) 2017-09-13
AU2018203985B2 (en) 2019-09-19
AU2014239562A1 (en) 2015-08-27
US10266559B2 (en) 2019-04-23

Similar Documents

Publication Publication Date Title
EA201591281A1 (ru) Рибонуклеиновые кислоты с 4'-тиомодифицированными нуклеотидами и связанные с ними способы
CY1124742T1 (el) 4'-φθορο-νουκλεοσιδια, 4'-φθορο-νουκλοεοτιδια και αναλογα αυτων για τη θεραπευτικη αγωγη toy hcv
CY1124327T1 (el) Τροποποιηση της εκφρασης του ιου ηπατιτιδας β (hbv)
CL2019000732A1 (es) Tratamiento avv de la enfermedad de huntington.
BR112017007765A2 (pt) composições de adenosina deaminase-2 (ada2), variantes do mesmo e métodos de usar o mesmo
MX2017014908A (es) Proteinas de union triespecificas y metodos de uso.
MX359953B (es) Ácido nucleico que comprende o que codifica un tallo-rizo de histona y una secuencia poli (a) o una señal de poliadenilación para incrementar la expresión de una proteína terapéutica codificada.
WO2015106128A3 (en) Rnai agents modified at the 4'-c-position
CY1119410T1 (el) Βελτιστοποιημενα μονοκλωνικα αντισωματα εναντι του αναστολεα της οδου του ιστικου παραγοντα (tfpi)
EA201490994A1 (ru) Функционально-модифицированные олигонуклеотиды и их субъединицы
MX359548B (es) Agentes de iarn modificados.
EA201690881A1 (ru) Соединения-ингибиторы аутотаксина
BR112016004095A2 (pt) administração de enzimas de empobrecimento de quinurenina para a terapia contra tumores
EA201790267A1 (ru) Новые модуляторы киназ
EA201790802A1 (ru) Соединения против tnf
MA32771B1 (fr) Mutants fgf21 et leurs utilisations
BR112015010955A2 (pt) inibidores de glutaminase heterocíclica
MX2012010244A (es) Composiciones y metodos de tratamiento para enfermedad de parkinson mediante transferencia del gen bndf-flag a traves del poliplex de neurotensina a neuronas dopaminergicas nigrales.
BR112018014288A2 (pt) métodos e composições para o tratamento de doença neurológica
WO2014111458A3 (en) Factor 1 protein, factor 2 protein and inhibitors thereof for use in treating or preventing diseases
EA201201464A1 (ru) Новая комбинированная терапия для лечения онкологических и фиброзных заболеваний
MX2018004043A (es) Prevencion, tratamiento y reversion de enfermedad usando cantidades terapeuticamente efectivas de acidos grasos activados.
WO2014151456A3 (en) Treatment of inflammatory diseases
AR107579A1 (es) Composiciones y métodos para disminuir la expresión de tau
MX2017005861A (es) Metodos para el control transcripcional objetivo en regiones del super mejorador.