ZA201801682B - Antisense nucleic acids - Google Patents

Antisense nucleic acids

Info

Publication number
ZA201801682B
ZA201801682B ZA2018/01682A ZA201801682A ZA201801682B ZA 201801682 B ZA201801682 B ZA 201801682B ZA 2018/01682 A ZA2018/01682 A ZA 2018/01682A ZA 201801682 A ZA201801682 A ZA 201801682A ZA 201801682 B ZA201801682 B ZA 201801682B
Authority
ZA
South Africa
Prior art keywords
nucleic acids
antisense nucleic
antisense
acids
nucleic
Prior art date
Application number
ZA2018/01682A
Other languages
English (en)
Inventor
Enya Yukiko
Tone Yuichiro
Takeda Shin'ichi
AOKI Yoshitsugu
Original Assignee
Nippon Shinyaku Co Ltd
Nat Center Neurology & Psychiatry
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 Nippon Shinyaku Co Ltd, Nat Center Neurology & Psychiatry filed Critical Nippon Shinyaku Co Ltd
Publication of ZA201801682B publication Critical patent/ZA201801682B/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/712Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/313Phosphorodithioates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/314Phosphoramidates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3212'-O-R Modification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/323Chemical structure of the sugar modified ring structure
    • C12N2310/3233Morpholino-type ring
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Neurology (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)
  • Medicinal Preparation (AREA)
ZA2018/01682A 2015-09-15 2018-03-12 Antisense nucleic acids ZA201801682B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2015182145 2015-09-15
PCT/JP2016/077305 WO2017047707A1 (ja) 2015-09-15 2016-09-15 アンチセンス核酸

Publications (1)

Publication Number Publication Date
ZA201801682B true ZA201801682B (en) 2020-07-29

Family

ID=58289325

Family Applications (1)

Application Number Title Priority Date Filing Date
ZA2018/01682A ZA201801682B (en) 2015-09-15 2018-03-12 Antisense nucleic acids

Country Status (29)

Country Link
US (4) US10144931B2 (enExample)
EP (2) EP3778895A1 (enExample)
JP (5) JP6384845B2 (enExample)
KR (3) KR20220053048A (enExample)
CN (3) CN113913426B (enExample)
AU (1) AU2016324800B2 (enExample)
CA (1) CA2996280C (enExample)
CO (1) CO2018002557A2 (enExample)
CY (1) CY1123119T1 (enExample)
DK (1) DK3351633T3 (enExample)
ES (1) ES2808049T3 (enExample)
HR (1) HRP20201125T1 (enExample)
HU (1) HUE050061T2 (enExample)
IL (1) IL258065B (enExample)
LT (1) LT3351633T (enExample)
MX (1) MX391304B (enExample)
MY (1) MY185390A (enExample)
PH (1) PH12018500568B1 (enExample)
PL (1) PL3351633T3 (enExample)
PT (1) PT3351633T (enExample)
RS (1) RS60493B1 (enExample)
RU (1) RU2724554C2 (enExample)
SG (1) SG11201802138TA (enExample)
SI (1) SI3351633T1 (enExample)
SM (1) SMT202000379T1 (enExample)
TW (1) TWI725990B (enExample)
UA (1) UA123359C2 (enExample)
WO (1) WO2017047707A1 (enExample)
ZA (1) ZA201801682B (enExample)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HUE050061T2 (hu) * 2015-09-15 2020-12-28 Nippon Shinyaku Co Ltd Antiszensz nukleinsav
IL295755A (en) 2015-10-09 2022-10-01 Wave Life Sciences Ltd Oligonucleotide compositions and methods thereof
CA3108282A1 (en) 2018-08-02 2020-02-06 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating dystrophinopathies
SG11202100928QA (en) 2018-08-02 2021-02-25 Dyne Therapeutics Inc Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy
US12018087B2 (en) 2018-08-02 2024-06-25 Dyne Therapeutics, Inc. Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject
US11168141B2 (en) 2018-08-02 2021-11-09 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating dystrophinopathies
GB201821269D0 (en) * 2018-12-28 2019-02-13 Nippon Shinyaku Co Ltd Myostatin signal inhibitor
WO2020219820A1 (en) 2019-04-25 2020-10-29 Avidity Biosciences, Inc. Nucleic acid compositions and methods of multi-exon skipping
IL293997A (en) * 2019-12-19 2022-08-01 Nippon Shinyaku Co Ltd Antistrand nucleic acids that allow exon skipping
IL295967A (en) * 2020-02-28 2022-10-01 Nippon Shinyaku Co Ltd Antisense nucleic acids for splicing on exon 51
IL307937A (en) 2021-04-30 2023-12-01 Sarepta Therapeutics Inc Treatment methods for muscular dystrophy
WO2022270585A1 (ja) * 2021-06-23 2022-12-29 日本新薬株式会社 アンチセンスオリゴマーの組み合わせ
JP2024525608A (ja) 2021-07-09 2024-07-12 ダイン セラピューティクス,インコーポレーテッド ジストロフィン異常症を処置するための筋標的化複合体および製剤
US11771776B2 (en) 2021-07-09 2023-10-03 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating dystrophinopathies
US11969475B2 (en) 2021-07-09 2024-04-30 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy
US11638761B2 (en) 2021-07-09 2023-05-02 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy
EP4458833A4 (en) 2021-12-27 2025-12-31 Nippon Shinyaku Co Ltd PROCESS FOR THE PRODUCTION OF OLIGONUCLEIC ACID COMPOUNDS
WO2023168427A1 (en) 2022-03-03 2023-09-07 Yale University Compositions and methods for delivering therapeutic polynucleotides for exon skipping
CN119013401A (zh) 2022-03-17 2024-11-22 萨勒普塔医疗公司 二氨基磷酸酯吗啉代寡聚物缀合物
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2567664A (en) 1948-04-22 1951-09-11 Willis G Ewell Chicken culling device
AU655164B2 (en) 1989-12-20 1994-12-08 Antivirals Inc. Uncharged morpholino-based polymers having phosphorous-containing chiral intersubunit linkages
JP2924179B2 (ja) 1993-02-19 1999-07-26 日本新薬株式会社 グリセロール誘導体,デバイス及び医薬組成物
JP2000325085A (ja) * 1999-05-21 2000-11-28 Masafumi Matsuo デュシェンヌ型筋ジストロフィー治療剤
JP4836366B2 (ja) * 2000-08-25 2011-12-14 雅文 松尾 デュシェンヌ型筋ジストロフィー治療剤
US6727355B2 (en) * 2000-08-25 2004-04-27 Jcr Pharmaceuticals Co., Ltd. Pharmaceutical composition for treatment of Duchenne muscular dystrophy
EP1191097A1 (en) 2000-09-21 2002-03-27 Leids Universitair Medisch Centrum Induction of exon skipping in eukaryotic cells
EP2392660A3 (en) 2002-11-25 2012-03-28 Masafumi Matsuo ENA Nucleic Acid Drugs Modifying Splicing in mRNA Precursor
AU2003225410A1 (en) * 2003-03-21 2004-10-11 Academisch Ziekenhuis Leiden Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure
EP2933332A1 (en) 2004-06-28 2015-10-21 The University Of Western Australia Antisense oligonucleotides for inducing exon skipping and methods of use thereof
WO2006038608A1 (ja) 2004-10-05 2006-04-13 Nippon Shinyaku Co., Ltd. オリゴ二本鎖rna及び医薬組成物
EP1886688A4 (en) 2005-05-30 2013-01-09 Nippon Shinyaku Co Ltd METHOD FOR PRODUCING PREPARATION OF A NUCLEIC ACID-CONTAINING COMPLEX
EP1857548A1 (en) 2006-05-19 2007-11-21 Academisch Ziekenhuis Leiden Means and method for inducing exon-skipping
JP5347510B2 (ja) 2007-02-05 2013-11-20 日本新薬株式会社 ポリエチレングリコール誘導体
US20100016215A1 (en) * 2007-06-29 2010-01-21 Avi Biopharma, Inc. Compound and method for treating myotonic dystrophy
ES2639852T3 (es) * 2007-10-26 2017-10-30 Academisch Ziekenhuis Leiden Medios y métodos para contrarrestar los trastornos musculares
RU2606627C2 (ru) 2007-11-15 2017-01-10 Серепта Терапьютикс,Инк. Способ синтеза морфолиновых олигомеров
EP2119783A1 (en) 2008-05-14 2009-11-18 Prosensa Technologies B.V. Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means
US8084601B2 (en) 2008-09-11 2011-12-27 Royal Holloway And Bedford New College Royal Holloway, University Of London Oligomers
BR122020021379B1 (pt) 2008-10-24 2021-05-11 Sarepta Therapeutics, Inc. oligômero morfolino fosforodiamidato, composição que compreende o mesmo e uso do dito oligômero para tratar distrofia muscular
AU2009310557B2 (en) 2008-10-27 2014-09-11 Academisch Ziekenhuis Leiden Methods and means for efficient skipping of exon 45 in Duchenne Muscular Dystrophy pre-mRNA
EP2421971B1 (en) * 2009-04-24 2016-07-06 BioMarin Technologies B.V. Oligonucleotide comprising an inosine for treating dmd
ITTO20090487A1 (it) * 2009-06-26 2010-12-27 Univ Ferrara Oligonucleotidi antisenso atti ad indurre lo skipping esonico e loro impiego come medicamento per il trattamento della distrofia muscolare di duchenne (dmd)
US20120270930A1 (en) * 2009-10-29 2012-10-25 Academisch Ziekenhuis Leiden H.O.D.N. Lumc Methods and compositions for dysferlin exon-skipping
TR201816523T4 (tr) 2009-11-12 2018-11-21 Univ Western Australia Patolojilerin tedavisine yönelik antisens moleküller ve yöntemler.
TWI541024B (zh) 2010-09-01 2016-07-11 日本新藥股份有限公司 反義核酸
EP2672977A1 (en) * 2011-02-08 2013-12-18 The Charlotte-Mecklenburg Hospital Authority d/b/a Carolina Healthcare System Antisense oligonucleotides
CA2861247C (en) * 2011-12-28 2021-11-16 Nippon Shinyaku Co., Ltd. Antisense nucleic acids
NZ627896A (en) * 2012-01-27 2016-11-25 Biomarin Technologies B V Rna modulating oligonucleotides with improved characteristics for the treatment of duchenne and becker muscular dystrophy
EP2870246B1 (en) * 2012-07-03 2019-09-11 BioMarin Technologies B.V. Oligonucleotide for the treatment of muscular dystrophy patients
US20140329762A1 (en) 2013-03-15 2014-11-06 Sarepta Therapeutics, Inc. Compositions for treating muscular dystrophy
DK3118311T3 (en) 2014-03-12 2019-03-11 Nippon Shinyaku Co Ltd Antisense nucleic acid
JP2015182145A (ja) 2014-03-20 2015-10-22 キヤノン株式会社 ロボットシステムの制御方法、およびロボットシステム
MX373052B (es) 2014-06-17 2020-05-11 Nippon Shinyaku Co Ltd Acidos nucleicos antisentido.
HUE050061T2 (hu) * 2015-09-15 2020-12-28 Nippon Shinyaku Co Ltd Antiszensz nukleinsav

Also Published As

Publication number Publication date
AU2016324800B2 (en) 2022-02-24
SMT202000379T1 (it) 2020-09-10
PL3351633T3 (pl) 2020-11-02
LT3351633T (lt) 2020-08-10
CN113913426B (zh) 2024-08-02
JP2024038104A (ja) 2024-03-19
JPWO2017047707A1 (ja) 2018-07-05
CA2996280A1 (en) 2017-03-23
EP3351633A1 (en) 2018-07-25
CN113913426A (zh) 2022-01-11
RU2724554C2 (ru) 2020-06-23
CN113930426A (zh) 2022-01-14
KR102473431B1 (ko) 2022-12-01
MX2018002955A (es) 2018-05-02
RS60493B1 (sr) 2020-08-31
US10144931B2 (en) 2018-12-04
MY185390A (en) 2021-05-17
EP3351633A4 (en) 2019-09-04
PH12018500568A1 (en) 2018-09-24
SG11201802138TA (en) 2018-04-27
WO2017047707A1 (ja) 2017-03-23
PT3351633T (pt) 2020-07-29
JP2022033738A (ja) 2022-03-02
PH12018500568B1 (en) 2022-09-14
US10851373B2 (en) 2020-12-01
RU2018113276A3 (enExample) 2020-02-06
DK3351633T3 (da) 2020-08-03
IL258065A (en) 2018-05-31
RU2018113276A (ru) 2019-10-16
CN108026531B (zh) 2021-09-14
IL258065B (en) 2022-02-01
CA2996280C (en) 2024-05-07
US20190040387A1 (en) 2019-02-07
TWI725990B (zh) 2021-05-01
CN108026531A (zh) 2018-05-11
US20240368597A1 (en) 2024-11-07
JP6977998B2 (ja) 2021-12-08
AU2016324800A1 (en) 2018-04-05
MX391304B (es) 2025-03-21
BR112018004970A2 (pt) 2018-10-09
HRP20201125T1 (hr) 2020-10-30
US11981894B2 (en) 2024-05-14
JP2026032058A (ja) 2026-02-25
UA123359C2 (uk) 2021-03-24
EP3351633B1 (en) 2020-06-24
KR101968880B1 (ko) 2019-04-12
US20210147839A1 (en) 2021-05-20
JP2018183178A (ja) 2018-11-22
NZ740562A (en) 2021-11-26
KR20220053048A (ko) 2022-04-28
KR20190040098A (ko) 2019-04-16
SI3351633T1 (sl) 2020-09-30
HUE050061T2 (hu) 2020-12-28
CO2018002557A2 (es) 2018-05-31
CY1123119T1 (el) 2021-10-29
TW201718858A (zh) 2017-06-01
ES2808049T3 (es) 2021-02-25
JP6384845B2 (ja) 2018-09-05
US20180265866A1 (en) 2018-09-20
EP3778895A1 (en) 2021-02-17
KR20180043244A (ko) 2018-04-27

Similar Documents

Publication Publication Date Title
IL258065B (en) Nucleic acids against the coding strand
ZA201700142B (en) Antisense nucleic acids
ZA201605864B (en) Antisense nucleic acids
ZA201905396B (en) Trans-replicating rna
GB201507119D0 (en) Nucleic Acid Construct
GB201507115D0 (en) Nucleic Acid Construct
GB201507111D0 (en) Nucleic acid construct
GB201503408D0 (en) Oligonucleotides
GB201507104D0 (en) Nucleic acid construct
GB201507108D0 (en) Nucleic acid construct
GB201502739D0 (en) Heaters
IL257831A (en) Diplospore garden
GB201504124D0 (en) Oligonucleotides
SG10201913477UA (en) G-quadruplex-containing antisense oligonucleotides
GB201517241D0 (en) DNA modification
IL257500A (en) Altered cullin1 gene
SG10201609048RA (en) Antisense oligonucleotides
GB2536446B (en) PCR method
AU365197S (en) Heater
PT3318817T (pt) Aquecedor
GB201516505D0 (en) Antisense oligonucleotides
GB201508733D0 (en) Antisense oligonucleotides
GB201515680D0 (en) Heater
IL238379A0 (en) heater