WO1998039352A1 - Nouveaux analogues de bicyclonucleoside et d'oligonucleotide - Google Patents

Nouveaux analogues de bicyclonucleoside et d'oligonucleotide Download PDF

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WO1998039352A1
WO1998039352A1 PCT/JP1998/000945 JP9800945W WO9839352A1 WO 1998039352 A1 WO1998039352 A1 WO 1998039352A1 JP 9800945 W JP9800945 W JP 9800945W WO 9839352 A1 WO9839352 A1 WO 9839352A1
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PCT/JP1998/000945
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French (fr)
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Takeshi Imanishi
Satoshi Obika
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Takeshi Imanishi
Satoshi Obika
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Application filed by Takeshi Imanishi, Satoshi Obika filed Critical Takeshi Imanishi
Priority to AU61209/98A priority Critical patent/AU720472B2/en
Priority to EP98905804.5A priority patent/EP1013661B2/en
Priority to CA002283509A priority patent/CA2283509C/en
Priority to DK98905804.5T priority patent/DK1013661T4/en
Priority to DE98905804T priority patent/DE98905804T1/de
Priority to AT98905804T priority patent/ATE541576T2/de
Priority to US13/533,781 priority patent/USRE44779E1/en
Priority to US09/380,638 priority patent/US6268490B1/en
Priority to ES98905804T priority patent/ES2380354T5/es
Publication of WO1998039352A1 publication Critical patent/WO1998039352A1/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • 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

Definitions

  • the present invention relates to novel nucleoside and nucleotide analogs, and more particularly to nucleotide analogs suitable for antisense molecules.
  • Antisense oligonucleotides are one of the most promising fields in recent years as pharmaceuticals, as they specifically regulate the expression of unwanted genes.
  • the antisense method is based on the concept of controlling the flow of so-called centralola dogma using DNA ⁇ RNA ⁇ protein using an antisense oligonucleotide.
  • nucleic acid derivatives and analogs have been synthesized and studied. For example, phosphorothioate in which the oxygen atom on the phosphorus atom has been replaced by an ⁇ atom, methylphosphonate in which the methyl group has been replaced by a methyl group, and more recently, those in which the phosphorus atom has been replaced by a carbon atom, and also the structure of the sugar moiety Some have been synthesized, and others have been modified with modified nucleobases. In any case, derivatives and analogs that are sufficiently satisfactory in terms of stability in vivo, ease of synthesis, and sequence specificity (selective control of specific gene expression only) Is currently not available.
  • the inventors of the present invention designed a nucleic acid analog having a sugar moiety conformation immobilized thereon, which is considered to be useful in the antisense method, and designed a nucleoside analog having a unit structure thereof. The synthesis was performed, and it was confirmed that the oligonucleotide analogs prepared using this were extremely useful as antisense molecules.
  • FIG. 1 is a chart showing a time-dependent change in ultraviolet absorption (260 nm) when a natural oligonucleotide is decomposed with exonuclease.
  • FIG. 2 is a chart showing the change over time in the ultraviolet absorption (260 nm) when the oligonucleotide (X 2) of the present invention is decomposed with exonuclease.
  • nucleoside analog of the present invention can be represented by the following general formula (I)
  • B is pyrimidine or purine nucleobase or an analog thereof, and X and Y are the same or different and are hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, or an acyl group. Or a silyl group], or an amidite derivative thereof.
  • the alkyl group refers to a linear or branched alkyl group having 1 to 20 carbon atoms, such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, and a t-alkyl group. Butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and the like.
  • the alkenyl group refers to a linear or branched alkenyl group having 2 to 20 carbon atoms, and examples thereof include a vinyl group, an aryl group, a butenyl group, a pentenyl group, a geranyl group, and a farnesyl group. .
  • the alkynyl group refers to a linear or branched alkynyl group having 2 to 20 carbon atoms, and includes, for example, an ethynyl group, a propynyl group, a butynyl group and the like.
  • the cycloalkyl group refers to a cycloalkyl group having 3 to 8 carbon atoms, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclohexyl group, and a cyclooctyl group.
  • Heterocyclic groups in which one or more arbitrary methylene on the ring of the cycloalkyl group is substituted with an oxygen atom, a sulfur atom, or a nitrogen atom substituted with an alkyl group are also included, and examples include a tetrahydroviranyl group.
  • the aryl group means a monovalent substituent obtained by removing one hydrogen atom from an aromatic heterocyclic group or an aromatic hydrocarbon group, and preferably, by removing one hydrogen atom from an aromatic hydrocarbon group.
  • a monovalent substituent means, for example, a phenyl group, a tolyl group, a xylyl group, a biphenyl group, a naphthyl group, an anthryl group, a phananthryl group and the like.
  • the carbon atom on the ring of the aryl group may be substituted by one or more groups such as a halogen atom, a lower alkyl group, a hydroxyl group, an alkoxy group, an amino group, a nitro group and a trifluoromethyl group.
  • substituents include a halogen atom, a hydroxyl group, an amino group, an alkoxy group, an aryloxy group and the like.
  • An aralkyl group is a group in which an alkyl group is bonded to an aralkyl group, and the aralkyl group may be substituted.
  • An aralkyl group which may be substituted is a group in which an aralkyl group is bonded to an aralkyl group, wherein at least one hydrogen atom of an aryl group and an alkyl group is substituted with the following substituent. Means a good group.
  • substituent include an acyl group, an amino group, an aryl group, an alkyl group, a cycloalkyl group, an alkoxy group, a hydroxyl group, a nitro group, and a halogen atom.
  • the amino group may or may not be substituted.
  • the substituted amino group include an alkylamino group, an arylamino group, and an acylamino group.
  • alkoxy groups include methoxy, ethoxy, n-propoxy, i-pro Examples include a oxy group, an n-butoxy group, an i-butoxy group, an s-butoxy group, a t-butoxy group, a pentyloxy group, a hexyloxy group, and a phenoxy group.
  • Halogen atoms include fluorine, chlorine, bromine and iodine.
  • aralkyl group examples include, for example, a trityl group, a benzyl group, a phenethyl group, a tritylmethyl group, a diphenylmethyl group, a naphthylmethyl group, and a 4,4′-dimethoxytrityl (DMTr) group. Is the DMT r group.
  • acetyl group examples include an acetyl group, a formyl group, a propionyl group, a benzoyl group, and a benzyloxycarbonyl group.
  • silyl group examples include a trialkylsilyl group, and preferably a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, a t-butyldimethylsilyl group, a t-butyldiphenylsilyl group, and the like. Preferably it is a trimethylsilyl group.
  • the nucleotide analog of the present invention has the general formula (la)
  • ⁇ is a pyrimidine or purine nucleobase or an analog thereof
  • BB are the same or different and is a pyrimidine or purine nucleic acid base or their analogues
  • R represents hydrogen, hydroxyl, Ri halogen or alkoxy groups der
  • WW 2 are the same or different and are hydrogen, an alkyl group , An alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group, an aryl group, an acyl group, a silyl group or a natural nucleoside via a phosphoric acid residue or a phosphoric diester bond, a synthetic nucleoside, or an oligo containing these nucleosides a nucleotide or Helsingborg nucleotide
  • n 1 or n 2 are the same or different, is an integer of 0-5 0
  • N 3 is an integer of 1 to 5 0, where, n When 1 and / or n 2 is 2 or more, B 1 and B may not be the same, and R may not be the same.
  • the pyrimidine or purine nucleobase is thymine, peracyl, cytosine, adenine, guanine and derivatives thereof.
  • nucleond analog and nucleotide analog of the present invention can be synthesized as follows ( (1) Synthesis of nucleoside analog) O— 98/39352
  • the second method is based on D-ribose [3] AGM Barrett et al., J. Org. Chem., 55, 3853 (1990); 4) GH Jones et al., Ibid., 44, 1309 (1979) )], Via compound 13. That is, compound 13 is converted into compound 16 in three steps, and the ring-closing reaction under basic conditions yields the target methylglycol. The sil compound 17 was obtained. Substitution of the OMe group at position 1 of this compound with various natural nucleobases or non-natural nucleobase analogs is possible by various methods already developed. For example, methods such as the following compounds 17 to 20 can be used.
  • a third method is to use diacetone D-glucose, which is obtained from D-glucose in one step and is commercially available, as a starting material.
  • Reference 5 Compound 31 is prepared according to RD Youssefyeh, JPH Verheyden and JG Moffatt., J. Org. Chem., 44, 1301-1309 (1979). Then, as shown in the following formula, compound 31 was stepwise protected with two kinds of primary hydroxyl groups with t-butyldiphenylsilyl group and P-toluenesulfonyl group, and acetylated to give compound 34.
  • Compound 8 is reacted with 2-cyanoethyl-N, N, ⁇ ', N * -tetraisopropylphosphoramidite to obtain an amide 21 and then combined with a natural nucleoside amidite to form an automatic DNA synthesizer. Is used to synthesize various oligonucleotide analogs.
  • the synthesized crude product is purified using Oligopak and reversed-phase chromatography columns, and the purity of the purified product is confirmed by HPLC analysis.
  • One or more monomer units of compound 8 can be present in the oligonucleotide analog. In addition, it may be present at two or more positions in the oligonucleotide analog in an isolated state via one or more natural nucleotides. According to the present invention, it is possible to synthesize an antisense molecule in which the nucleotide analog (nucleoside analog) of the present invention is introduced at a required position in a required number (length). The total length of the oligonucleotide analog is 2 to 50, preferably 10 to 30, nucleoside units.
  • oligonucleotide analogs are not easily degraded by various nucleases, and can exist in the living body for a long time after administration to the living body. For example, they form stable duplexes with messenger RNA to inhibit the biosynthesis of pathogenic proteins, or form triplexes with double-stranded DNA in the genome to form messenger RNAs. Inhibits transcription to It will also be able to control the growth of infected viruses. From these facts, the oligonucleotide analogs (antisense molecules) using the nucleoside analogs of the present invention can be used as pharmaceuticals for treating diseases by inhibiting the function of specific genes, such as antitumor agents and antiviral agents. Is expected to be useful.
  • the antisense molecule using the nucleotide (nucleotide) analog of the present invention may be formulated into a parenteral administration preparation by combining conventional auxiliaries such as a buffer and / or a stabilizer, or a ribosome preparation. Can be.
  • a common pharmaceutical carrier can be compounded to prepare an ointment, cream, solution, salve or the like.
  • Compound 3 White powder rap 119-120 ° C.
  • Methyl 5-0-(t-butyldiphenylsilyl) synthesis of 1-3-0,4-C-methylene-1 / 3-D-ribofuranoside (18)
  • Triethylamine (3.71 ml, 26.6 mraol) and t-butyl were added to a methylene chloride solution (50 ml) of compound 31 (2.50 g, 8.08 mmol) prepared according to the above reference 5) under a nitrogen stream and ice cooling.
  • Diphenylsilyl chloride (6.94 ml, 26.7 mmol) was added, and the mixture was stirred at room temperature for 10.5 hours. After adding a saturated aqueous solution of sodium bicarbonate to the reaction solution, the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated saline solution and dried over sodium sulfate.
  • triethylamine (395 ⁇ , 2.83 mmol) and p-toluenesulfonyl chloride (139.2) were added to a solution of 32 (250 mg, 0.456 mmol) in methylene chloride. mg, 0.730 mmol) and 4-dimethylaminopyridine (8.92 mg, 0.0730 mmol), and the mixture was stirred at room temperature for 15.5 hours. After adding a saturated aqueous solution of sodium bicarbonate to the reaction solution, the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate.
  • acetic anhydride (6.0 ml, 63.6 mmol) and concentrated sulfuric acid (56 jul, 1.10 mol) were added to an acetic acid solution (56 ml) of 34 (3.70 g, 5.27 mmol), and the mixture was stirred at room temperature for 2 hours. did. After the reaction solution was poured into ice water (300 ml) and stirred for 30 minutes, saturated saline was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate.
  • tetrabutylammonium fluoride (1.0 M in THF, 379 ⁇ , 0.379 raol) was added to a solution of 37 (188.7 mg, 0.316 mmol) in tetrahydrofuran (1 ml), and the mixture was stirred at room temperature for 2.5 hours. did.
  • the reaction solution was evaporated under reduced pressure, and the crude product obtained was purified by silica gel column chromatography (AcOEt-hexane, 1: 1 ⁇ 1: 0) to give a white powder (38) (94.6 mg, 0.262 mg). Ol, 83%).
  • the oligomer was cleaved from the support by treatment with concentrated aqueous ammonia according to a conventional method, the cyanoethyl group on the phosphorus atom was removed, and the protecting groups of adenine, guanine and cytosine were removed.
  • the resulting 5 '— 0— DMT r-oligonucleotide analog was purified on reverse phase column chromatography (Millipore, Oligo-Pak TM SP) by removing the DMT r group with 5 ml of trifluoroacetic acid.
  • the target oligonucleotide analog was obtained.
  • the various oligonucleotide analogs synthesized in Example 2 were used as antisense strands, and the melting temperature (Tm value) of annealed natural strands of DNA or RNA was measured to determine the melting temperature (Tm value) of the present invention.
  • Tm value melting temperature
  • the final concentrations were NaC 110 Om.
  • a nitrogen stream was passed through the cell chamber of the spectrophotometer (Shimadzu UV-2100PC) to prevent dew condensation, the sample solution was gradually cooled to 5 ° C, and kept at 5 ° C for another 20 minutes before measuring. It has started.
  • the sample temperature was increased by 0.2 ° C per minute to 90 ° C, and ultraviolet absorption at 260 nm was measured at 0.1 ° C intervals.
  • the cell was used with a lid, and the measurement was performed with one drop of mineral oil added to the surface of the sample solution.
  • oligomers in which one or two units (X) of the nucleoside analog (general formula (la)) of the present invention were introduced into a natural DNA chain, hybridized with a complementary DNA oligomer. 2 to 7 degrees (approximately 2 times per modified residue) as compared to the natural chain as assessed by Tm value, and as high as 11 degrees for all T substituted with X (X6) did.
  • the increase in the Tm value of the oligomer introduced with one or two oligomers was 410 to 10 degrees (4 to 6 degrees per modified residue) compared to the natural chain.
  • a buffer solution of snake venom phosphodiesterase (0.003 U / ml, 400 1) was mixed with the buffer solution of the oligonucleotide kept at C (10 M, 400 H). The mixed solution was placed in a quartz cell (800 il) maintained at 37 ° C, and the increase in ultraviolet absorption (260 nm) due to the decomposition of the oligonucleotide was measured over time using SHIMADZU UV-2100PC.
  • the buffer composition used was 0.1 mM Tris-HCl (pH 8.6), 0.1 mM NaCl, and 14 mM MgCl 2, and was sufficiently degassed before measurement.
  • FIG. 1 naturally chain
  • FIG. 2 X 2
  • the UV absorption value of the natural chain became constant at about 30 minutes after the start of the oxygen reaction, and became constant at about 90 minutes for X2.
  • this analog provides an oligonucleotide analog antisense molecule that is not easily hydrolyzed by an enzyme in a living body, has high binding ability to a sense strand, and is easy to synthesize.
  • Sequence type nucleotide, nucleotide analog
  • Sequence type nucleotide, nucleotide analog Number of strands: single strand
  • Sequence type nucleotide, nucleotide analog Number of strands: single strand
  • Sequence type nucleotide, nucleotide analog Number of strands: single strand
  • Sequence type nucleotide, nucleotide analog
  • Sequence type nucleotide, nucleotide analog
  • Sequence type nucleotide, nucleotide analog
  • Sequence type nucleotide, nucleotide analog Number of strands: single strand

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Description

明 細 書 新規ビシクロヌクレオシド及びォリゴヌクレオチド類縁体
[技術分野]
本発明は新規なヌクレオシド類縁体とヌクレオチド類縁体に関し、 更に詳細に はアンチセンス分子に適したヌクレオチド類縁体に関するものである。
[背景技術]
1 9 7 8年にアンチセンス分子がィンフルェンザウィルスの感染を阻害したと の報告が初めて成された。 以後、 ガン遺伝子発現や A I D S感染を阻害したとの 報告もなされている。 アンチセンスオリゴヌクレオチドが望ましくない遺伝子の 発現を特異的に制御することから、 医薬品として近年、 最も期待されている分野 の一つである。
アンチセンス法とは、 D N A→R N A→タンパク質という、 いわゆるセントラ ノレドグマの一連の流れをアンチセンスオリゴヌクレオチドを用いて制御しようと いう概念に基づいている。
しかしながら、 天然型オリゴヌクレオチドをアンチセンス分子としてこの方法に 適用した場合、 生体内の各種ヌクレア一ゼにより分解を受けたり、 細胞膜透過性 が高くないなどの問題が生じた。 そのため、 様々な核酸誘導体や類縁体が数多く 合成され、 研究が重ねられてきた。 例えば、 リン原子上の酸素原子をィォゥ原子 に置換したホスホロチォエート、 メチル基に置換したメチルホスホネート、 また 最近になっては、 リン原子も炭素原子で置換したもの、 さらには糖部の構造を変 換したもの、 核酸塩基を修飾したものなども合成されている。 しカヽし、 いずれの 場合も、 生体内での安定性、 合成の容易さ、 配列特異性 （特定の遺伝子発現のみ を選択的に制御する） などの点で十分に満足のいく誘導体や類縁体が得られてい ないのが現状である。
生体内でヌクレアーゼによる分解を受けにく く、 高い親和力で標的のメ ッセン ジャー R N Aに結合し、 その特異性に優れ、 よって特定の遺伝子の発現を効率よ く制御することのできるアンチセンス用の分子の創製が望まれている。
[発明の開示] 本発明の発明者らは、 アンチセンス法において有用と考えられる、 核酸におけ る糖部のコンホメーションの固定化を施したした核酸類縁体を設計し、 その単位 構造となるヌクレオシド類縁体の合成を行い、 これを用いて調製したオリゴヌク レオチド類縁体にアンチセンス分子として極めて有用であることを確認した。
[図面の簡単な説明]
第 1図は、 天然型のオリゴヌクレオチドをェキソヌクレアーゼで分解した時の 紫外部吸収 （2 6 0 n m) の経時変化を示すチャートである。
第 2図は、 本発明のオリゴヌクレオチド （X 2 ) をェキソヌクレアーゼで分解 した時の紫外部吸収 （2 6 0 n m) の経時的変化を示すチヤ一トである。
以下に本発明の詳細を説明する。
本発明のヌクレオシド類縁体の構造は下記の一般式 （ I ) で表すことができる
Figure imgf000004_0001
[式中、 Bはピリ ミジンもしくはプリン核酸塩基又はそれらの類縁体であり、 X及び Yは同一もしくは異なり、 水素、 アルキル基、 アルケニル基、 アルキニル 基、 シクロアルキル基、 ァラルキル基、 ァリール基、 ァシル基、 又はシリル基で ある] で表わされるヌクレオシド類縁体もしくはそれらのアミダイ ト誘導体であ
O o
アルキル基とは炭素数 1一 2 0の直鎖または分枝鎖状のアルキル基を示し、 例 えば、 メチル基、 ェチル基、 n—プロピル基、 i—プロピル基、 n—ブチル基、 t—ブチル基、 ペンチル基、 へキシル基、 ヘプチル基、 ォクチル基、 ノニル基、 デシル基等があげられる。 アルケニル基とは、 炭素数 2— 2 0の直鎖または分枝鎖状のアルケニル基を示 し、 例えば、 ビニル基、 ァリル基、 ブテニル基、 ペンテニル基、 ゲラニル基、 ファ ルネシル基等があげられる。
アルキニル基とは、 炭素数 2— 2 0の直鎖または分枝鎖状のアルキニル基を示 し、 例えば、 ェチニル基、 プロピニル基、 プチニル基等があげられる。
シクロアルキル基とは、 炭素数 3— 8のシクロアルキル基を示し、 例えば、 シ クロプロピル基、 シクロブチル基、 シクロペンチル基、 シクロへキシル基、 シク 口へプチル基、 シクロォクチル基等があげられる。 シクロアルキル基の環上の 1 つ以上の任意のメチレンが酸素原子や硫黄原子あるいはアルキル基で置換された 窒素原子に置換された複素環基も含まれ、 例えばテトラヒ ドロビラニル基などが あげられる。
ァリール基とは、 芳香族複素環基又は芳香族炭化水素基、 から水素原子 1個を 除いた 1価の置換基を意味し、 好ましくは、 芳香族炭化水素基から水素原子 1個 を除いた 1価の置換基を意味し、 例えば、 フエニル基、 トリル基、 キシリル基、 ビフヱニル基、 ナフチル基、 アントリル基、 フヱナントリル基等である。 また、 ァリール基の環上の炭素原子はハロゲン原子、 低級アルキル基、 水酸基、 アルコ キシ基、 アミノ基、 ニトロ基、 トリフルォロメチル基等の 1種以上の基によって 置換されていてもよい。 置換基としてはハロゲン原子、 水酸基、 アミノ基、 アル コキシ基、 ァリールォキシ基等があげられる。
ァラルキル基とは、 ァリール基にアルキル基が結合した基で、 ァラルキル基は 置換されていてもよい。 置換されていてもよいァラルキル基とはァリール基にァ ルキル基が結合した基で、 ァリ一ル基及びアルキル基の任意の 1つ以上の水素原 子が以下の置換基で置換されていてもよい基を意味する。 ここで置換基として は、 ァシル基、 アミノ基、 ァリール基、 アルキル基、 シクロアルキル基、 アルコ キシ基、 水酸基、 ニトロ基、 ハロゲン原子等がある。
ァミノ基は置換されていてもいなくてもよいが、 置換されているァミノ基の例 としてはアルキルアミノ基、 ァリールアミノ基、 ァシルァミノ基等がある。 アル コキシ基の例としては、 メ トキシ基、 エトキン基、 n—プロポキシ基、 i—プロ ポキシ基、 n—ブトキシ基、 i一ブトキン基、 s—ブトキシ基、 t一ブトキシ基、 ペンチルォキシ基、 へキシルォキシ基、 フヱノキシ基等がある。 ハロゲン原子と してはフッ素、 塩素、 臭素、 ヨウ素がある。
ァラルキル基の好ましい例としては、 例えばトリチル基、 ベンジル基、 フエネ チル基、 トリチルメチル基、 ジフヱニルメチル基、 ナフチルメチル基、 4 , 4 '一 ジメ トキシトリチル （D MT r ) 基等があるが、 特に好ましいのは D M T r基で ある。
ァシル基としては、 ァセチル基、 ホルミル基、 プロピオニル基、 ベンゾィル基、 ベンジルォキシカルボニル基等があげられる。 シリル基の例としては、 卜リアル キルシリル基があげられるが、 好ましくは、 トリメチルシリル基、 トリェチルシ リル基、 トリイソプロビルシリル基、 t—ブチルジメチルシリル基、 t—ブチル ジフエニルシリル基等があげられ、 更に好ましくはトリメチルシリル基である。 また、 本発明のヌクレオチド類縁体は、 一般式 （ l a )
Figure imgf000006_0001
[式中、 Βはピリ ミジンもしくはプリン核酸塩基又はそれらの類縁体である] で 表される構造を 1または 2以上有するオリゴヌクレオチドまたはポリヌクレオチ ド類縁体、 または、 一般式 （Π)
Figure imgf000007_0001
II
[式中、 B Bは同一または異なり、 ピリ ミジンもしくはプリン核酸塩基又は それらの類縁体であり、 Rは水素、 水酸基、 ハロゲン、 またはアルコキシ基であ り、 W W2は同一または異なり、 水素、 アルキル基、 アルケニル基、 アルキニ ル基、 シクロアルキル基、 ァラルキル基、 ァリール基、 ァシル基、 シリル基また はリン酸残基もしくはリン酸ジエステル結合を介した天然型ヌクレオシド、 合成 ヌクレオシドまたはこれらヌクレオンドを含むォリゴヌクレオチドもしくはボリ ヌクレオチドであり、 n 1または n 2は同一または異なり、 0〜 5 0の整数である
(ただし、 n 1または n 2が同時にゼロになることはない。 また、 n 2の全てが同 時にゼロになることはない。 ） 、 n 3は 1〜5 0の整数である、 ただし、 n 1およ び または n 2が 2以上の場合には B 1と Bは同一でなくてもよく、 Rも同一でな くてもよい] で表されるオリゴヌクレオチドもしくはポリヌクレオチド類縁体で あ 。
本発明における、 ピリ ミジンもしくはプリン核酸塩基とは、 チミン、 ゥラシル、 シ トシン、 アデニン、 グァニン及びそれらの誘導体である。
本発明のヌクレオンド類縁体及びヌクレオチド類縁体は次のように合成できる ( ( 1 ) ヌクレオシド類縁体の合成 O— 98/39352
Figure imgf000008_0001
Figure imgf000008_0002
roヽ y
Figure imgf000008_0003
a
ゥリジンから文献 [1) J. A. Secrist et al. , J. Am. Chem. So ， 101, 155 4 (1979); 2) G. H. Jones et al. , J. Org. Chem. , 44, 1309 (1979)] に従い 合成した化合物 1をトシルクロリ ド （Ts C 1 ) で 2個ある第一級アルコールの 一方のみをトシル化して化合物 2に導き、 酸加水分解して卜リオール体 3とした c 化合物 3はベンズアルデヒ ドと酸触媒下で縮合反応を行いベンジリデン化合物 4 として、 このものを四塩化チタン （T i C 14) 存在下にナトリゥムシァノボ口 ヒ ドリ ド （Na BH3CN) で還元すると化合物 5が得られた。 本化合物をテ卜 ラヒ ドロフラン （THF) 中でナトリウムへキサメチルジシラジド （N a HMD S) と反応させたところ、 ビシクロ化合物 6 (化合物 I ： Β-ゥラシル （U) , χ = Η, Υ =ベンジル） が得られた。 化合物 6をパラジウム炭素触媒下で接触 還元すると、 ジオール化合物 7 (化合物 （ I ) ； B = U, X = Y = H) が得られ、 更に、 4、 4' ージメ 卜キシ卜リチルク口リ ド （DMT r C 1 ) 処理すると卜リ チル体 8 (化合物 I ； B = U. X = DMT r, Y = H) が得られた。 化合物 6、 7及び 8は様々な化合物 Iの原料として利用することができる。
ゥリジン以外の天然 ·非天然を問わず様々な核酸塩基を有する化合物 （ I ) は 3通りの方法で合成することができる。
その一つは、 化合物 8からの変換である。 すなわち、 化合物 8をァセチル化し て化合物 9とした後、 1、 2、 4一トリァゾールと反応して化合物 10に導き、 加水分解すると化合物 11 (化合物 （I ) : B =シ トシン （C) . X = DMT r, Y = H) が得られた。 オリゴヌクレオチド合成の原料となる化合物 12 (化合物 ( I) ； B-ベンゾイルントシン （CBz)， X = DMT r, Y = H) は化合物 1 1のベンゾィル化で容易に得られる。
Figure imgf000009_0001
第二の方法は D—リボースから文献 [3) A. G. M. Barrett et al. , J. Org. Ch em. , 55, 3853(1990); 4) G. H. Jones et al. , ibid. , 44, 1309 (1979)] に従つ て容易に得られる化合物 13を経由する方法である。 すなわち、 化合物 13を 3 工程で化合物 16に導き、 塩基性条件下に閉環反応すると、 目的のメチルグリコ シル化合物 1 7が得られた。 本化合物の 1位 O M e基を天然の様々な核酸塩基や 非天然の核酸塩基類縁体に置換するには、 既に開発された種々の方法により可能 である。 例えば、 下式化合物 1 7から化合物 2 0のような方法が使用できる。
Figure imgf000011_0001
Me 2)
Figure imgf000011_0002
Figure imgf000011_0003
20 Wひ ·98/39352 さらに、 第三の方法としては、 D-グルコースから 1工程で得られ、 しかも市 販品であるジアセトン D-グルコースを出発原料とする方法である。 文献 5) R. D. Youssefyeh, J. P. H. Verheyden and J. G. Moffatt. , J. Org. Chem. , 44, 1301-1309 (1979) に従って化合物 31を調製する。 次いで、 化合物 31を下記 の式に示した通り、 2種の 1級水酸基を t-ブチルジフエニルシリル基、 P-トル エンスルホニル基で段階的に保護し、 ァセチル化処理して化合物 34に導いた。
Figure imgf000012_0001
Figure imgf000012_0002
Figure imgf000012_0003
化合物 34にトリメチルシリル化して活性化したチミン （2TMS · T) 、 ベ ンゾィルアデニン （2TMS . ABz) 、 イソプチリルグァニン （3TMS * GiBu) を別々に縮合させ、 下記の式に示すように、 化合物 5、 10、 14をそれぞれ高 収率で得た。 ついで、 これら縮合体は脱ァセチル化 （化合物 36、 41、 45) 、 5員環形成 （化合物 37、 42、 46) 、 脱シリル化 （化合物 38、 43、 47) 、 更に脱べンジル化して目的の化合物 39へと誘導した。
Figure imgf000013_0001
Figure imgf000013_0002
Figure imgf000013_0003
38: B= 39a: B=T 43: B=A Bz 39b: B=ABz 47: B=G iBu 39c: B=G旧 u ( 2 ) オリゴヌクレオチド類縁体の合成
化合物 8に 2—シァノエェチルー N, N, Ν' , N* ーテトライソプロピルホ スホロアミダイ トを作用させ、 ァミダイ 卜体 2 1を得、 このものと天然ヌクレオ シドアミダイ ト体とを組み合わせて、 D N A自動合成機を用いて種々のオリゴヌ クレオチド類縁体を合成する。 合成した粗生成物はオリゴパック、 逆相クロマト カラムを用いて精製し、 精製物の純度を H P L Cで分析することにより確認する
天 «ヌクレオシド
アミダイト オリゴヌクレオテド
Figure imgf000014_0001
CN
21
化合物 8のモノマーュニッ トは、 オリゴヌクレオチド類縁体の中に 1つ以上存 在させることができる。 また、 オリゴヌクレオチド類縁体の中の 2ケ所以上の位 置に、 1または 2以上の天然ヌクレオチドを介して隔離された状態で存在させて も良い。 本発明に依れば、 本発明のヌクレオチド類縁体 （ヌクレオシド類縁体） を必要な位置に必要な数 （長さ） で導入したアンチセンス分子を合成することが できる。 オリゴヌクレオチド類縁体全体の長さとしてヌクレオシド単位が 2〜5 0、 好ましくは 1 0〜3 0個である。
このようなオリゴヌクレオチド類縁体 （アンチセンス分子） は、 各種ヌクレア5 ーゼに対して分解されにく く、 生体への投与後、 長時間生体内に存在することが できる。 そして、 例えば、 メ ッセンジャー R N Aと安定な二重鎖を形成して病因 となるタンパク質の生合成を阻害したり、 ゲノム中の二重鎖 D N Aとの間で三重 鎖を形成して、 メ ッセンジャー R N Aへの転写を阻害する。 また、 感染したウイ ルスの増殖を抑えることも可能となる。 これらのことから、 本発明のヌクレオシド類縁体を用いたオリゴヌクレオチド 類縁体 （アンチセンス分子） は、 抗腫瘍剤、 抗ウィルス剤をはじめとした、 特定 遺伝子の働きを阻害して疾病を治療する医薬品としての有用性が期待される。 本発明のヌクレオチド （ヌクレオチド） 類縁体を用いたアンチセンス分子は、 例 えば、 緩衝剤および/または安定剤等の慣用の助剤を配合して非経口投与製剤と したり、 リボソーム製剤とすることができる。 また、 局所用の製剤としては、 慣 用の医薬用担体を配合して軟膏、 クリーム、 液剤、 または膏薬等に調剤できる。 ' 本発明のヌクレオシド類縁体ならびにヌクレオチド類縁体の合成を実施例およ び製造例により、 さらに詳しく説明する。 実施例では、 塩基としてゥラシルを主 として使用しているが、 他のプリン核酸塩基も同様に使用できる。
[実施例 1] ヌクレオシド類縁体の合成
(1) 2'. 3' -0-シクロへキシリデン -4'- (P-トルエンスルホニルォキシ
メチル） ゥリジン（2)の合成
窒素気流下、 文献既知化合物 1 ( 956 mg, 2.70 匪 ol ) の無水ピリジン溶液 ( 13.5 ml ) に室温で p -トルエンスルホニルクロリ ド （771 mg, 4.05 raraol)を 加え、 60 でで 5時間撹拌した。
反応溶液に飽和重曹水を加えた後、 ベンゼンで 3回抽出した。 有機層を飽和食 塩水で 1回洗浄後、 無水 MgS04 にて乾燥した。 溶媒を減圧留去し、 ベンゼンで 3回共沸し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （CHC13: MeOH = 15:1) により精製後、 ベンゼン一へキサンにて再沈澱し、 白色粉末とし て化合物 2 (808 mg, 1.59 ramol, 59%) を得た。
化合物 2 : 白色粉末 rap 104-106 °C (ベンゼン一へキサン）. IR (KBr): 33 26. 2929. 2850, 1628. 1577, 1544, 1437, 1311, 1244 era—1. !H-NMR (d6-acet one): δ 1.45-1.67 (瓶 m), 2.45 (3H, s), 3.71 (2H, ABq, J = 12 Hz), 4. 20 (2H, ABq, J = 11 Hz), 4.92 (1H， d, J' = 6 Hz), 5.05, 5.06 (1H, dd， J = 4, 6 Hz), 5.60 (1H, d, J = 7 Hz), 5.75 (1H, d, J = 4 Hz), 7.48 (2H, d, J = 8 Hz), 7.77 (1H, d, J = 8 Hz), 7.81 (2H, d, J = 8 Hz), 10.10 (1H, s, ). 13C-NMR (de-acetone): δ 21.5, 24.1, 24.5, 25.5, 34.8, 36.9, 63.5, 69.7, 82.5, 84.7, 87.8, 92.9, 102.9, 115.4， 128.8， 130.8, 133.9, 1 42.7, 145.9, 151.3, 163.5. ass(EI): m/z 481(M+- H20).
Anal. Calcd for C23H28N209S- 1/3 H20: C， 53.69; H, 5.61; N, 5.44; S, 6. 22. Found: C, 53.99 ;H, 5.48 :N, 5.42 :S, 6.10.
(2) 4'—(p-トルエンスルホニルォキシメチル）ゥリジン（3)の合成
化合物 2 (107 mg( 0.21 随 ol)を TFA— H2O (98:2, 1 ml) 中室温で 10 分 間撹拌した。 反応溶液を減圧留去し、 EtOHを加えて 3回共沸した。 得られた粗成 繽体をシリカゲルカラムクロマ卜グラフィ一（CHCl3:MeOH = 10:1)により精製し、 化合物 3(85. O mg, 0.20 随 ol, 94%)を得た。
化合物 3 : 白色粉末 rap 119-120 °C. IR v (KBr): 3227, 3060, 2932, 2837, 1709, 1508, 1464, 1252, 978, 835, 763. 556 era—1. ^-NMR (d6 - acetone) : 5 2.31 (3H, s), 2.84 (3H, s), 3.71 (2H, s), 4.13, 4.20 (2H, ABq, J = 11 Hz), 4.28, 4.31 (1H, dd, J' = 9, 6 Hz), 4.36 (1H, d, J' = 6 Hz), 5.54 (1 H, d, J' = 8 Hz), 5.75 (1H, d, J = 7 Hz), 7.32 (2H, d, J = 8 Hz), 7.67 (2H, d, J = 8 Hz), 7.70 (1H, d, J' = 8 Hz), 10.14 (1H, s). 13C-NMR (de- acetone)： δ 21.5, 63.7, 70.8, 72.7, 74.6, 86.8, 88.8, 103.1, 128.8, 130. 7. 133.9, 141.7, 145.8, 151.8, 163.9. Mass (EI): m/z 256 (M+- OTs) . (3) 2', 3'- O-ベンジリデン一 4' _(p-トルエンスルホニルォキシメチル） ゥリジン （4) の合成
窒素気流下、 化合物 3 (400 mg, 0.93 圆 ol) にべンズアルデヒ ド （2.4 ml, excess), 塩化亜鉛 （670 mg, 5.0 mmol)を加え室温にて 5時間撹拌した。 反応を 飽和重曹水により止め、 クロ口ホルムで抽出し、 飽和重曹水、 水、 飽和食塩水で 洗浄した。 有機層を無水硫酸ナトリウムで乾燥し、 溶媒留去後シリカゲルカラム クロマトグラフィー（CHC13 ： eOH = 40： 1) により精製し、 化合物 4 (380 rag, 0.74 ramol, 80¾ を得た。
化合物 4: 白色粉末. mp 99-102 。C (CH2C12-へキサン）. [«]□ 23- 26.7 ° (c = 1.0, CHC13). IR v (KBr)： 3059, 1691, 1460, 1362, 1269, 1218, 1177 cm-1. !H-NMR (CDC13) δ： 2.41 (3H, s), 3.25 (1H, br), 3.79 (2H, ra), 4.19 (2H, s), 5.09 (1H, d, J = 7 Hz), 5.28 (1H, dd, J = 3, 7 Hz), 5.60 (1H, d , J = 4 Hz), 5.73 (1H， d , J = 8 Hz), 5.94 (1H, s), 7.24 (1H, d, J = 8 H z), 7.38 (2H, d, J = 9 Hz), 7.42 (5H, br), 7.69 (2H, d, J = 9 Hz), 9.11 (1H, br). 13C-NMR ( CDC13): δ 21.6, 63.5, 68.3, 77.2. 82.8, 84.2, 87.7, 94.9, 102.6, 107.5, 126.5, 127.9, 128.5, 129.7, 132.2, 135.0, 143.0, 14 5.0, 150.4, 163.5.
Anal. Calcd for C24H24N209S'l/3 H20: C, 55.17; H, 4.76; N, 5.36; S， 6. 14. Found: 55.19 ;H, 4.66; N， 5.29; S， 5.98.
(4) 3'一 0—ベンジル一 4'—(p -トルエンスルホニルォキシメチル）
ゥリジン （5) の合成
窒素気流下、 化合物 4 (150 mg, 0.29 mraol)のァセトニトリル溶液 （3 ml)に シァノ水素化ホウ素ナトリウム （92 mg, 1.5 mmol)を室温にて加えた。 その後、 四塩化チタン （0.16 ml, 1.5 mmol)を氷冷下で滴下し室温にて 15 時間撹拌した。 反応液をクロ口ホルムに希釈して飽和重曹水、 水、 飽和食塩水で洗浄したのち有 機層を無水硫酸ナトリゥムで乾燥し、 溶媒留去後シリ力ゲル力ラムクロマトグラ フィー（CHC13 ： MeOH = 25:1)により精製し、 化合物 5 (112 mg, 0.22 mmol. 75¾) を得た。
化合物 5 : 無色結晶. mp 195-197°C (AcOEt-へキサン）. [a]o 23 -14.6° (c = 1.0, CHC13). I v (KBr)： 3033, 2885, 2820, 1726, 1470, 1361, 1274, 1175, 1119 cm-1. !H-NMR (CDC13) δ 2.40 (3H, s)， 3.59-3.77 (3H, m), 4. 10, 4.24 (2H, AB, J = 11 Hz), 4.32 (1H, d, J = 6 Hz), 4.56 (2H, m), 4.69 (1H, d, J = 11 Hz), 5.52 (1H, d , J = 6 Hz), 5.67 (1H, d . J = 8 Hz). 7.24 -7.29 (7H, m), 7.48 (1H, d, J = 8 Hz), 7.70 (2H, d, J = 9 Hz), 9.91 (1H, s). 13C-霞 (CDC13): δ 21.6, 63.2, 69.2, 73.6, 74.6, 78.1, 86.6, 92.9, 102.5. 127.9, 128.2, 128.3, 128.6. 129.9, 132.3, 136.9, 142.4, 145.2, 1 50.7, 163.8.
Anal. Calcd for C24H26N209S ： C, 55.59; H, 5.05; N, 5.40; S, 6.18.
Found: C, 55.41;H, 5.02; N, 5.32; S, 6.15. (5) 3'— 0—ベンジル一 2'—0, 4'— C—メチレンゥリ ジン （6) の合成 窒素気流下、 化合物 5 (80 mg, 0.16 mraol)の無水 T H F溶液 （1.5 ml) に室 温で NaHMDS (3.2 raraol) の無水ベンゼン懸濁液 （0.7 ml) を加え、 室温で 20 時 間撹拌した。 反応溶液に飽和重曹水を加え、 CHC13 にて抽出した。 有機層を飽和 食塩水で洗浄した後、 無水硫酸ナトリウムにて乾燥した。 溶媒を減圧留去し、 得 られた粗成績体をシリカゲルカラムクロマトグラフィー （CHC13 ： MeOH = 10:1) にて精製後、 MeOHにて再結晶し、 化合物 6 (41 mg, 0.10 raraol, 61%) を得た。 化合物 6 : 無色結晶. rap 217-219 °C (MeOH). [a]D 23+108.4 。 (c = 0.3, M eOH). IR v (KBr)： 3059, 2951, 1688, 1459, 1271. 1053 cm—1. 'H-N R (de - D MS0) δ： 3.75, 3.85 (2H, AB, J = 8 Hz), 3.77 (2H, d, J = 5 Hz), 3.92 (1H, s)， 4.44 (1H, s), 4.60 (2H, s), 5.39 (1H, t , J = 5 Hz), 5.48 (1H, s), 7. 31 (5H, ra)， 7.72 (1H, d, J = 8 Hz), 11.37 (1H, s). 13C-NMR (d6-DMS0): δ 56.0, 71.1, 71.6, 75.8, 76.5, 86.5, 88.3, 100.9, 127.4, 127.6, 128.2, 1 37.9, 139.0, 150.0, 163.3. Mass(EI): m/z 346 (M+, 1.1).
Anal. Calcd. for C17H18N206 ： C, 58.96; H, 5.24; N, 8.09.
Found: C, 58.67; H, 5.23; N, 8.05.
(6) 2'— O, 4'— C—メチレンゥリジン （7) の合成
化合物 6 (25 rag, 0.072 匪 ol)のメタノール溶液 (2.5 ml)に 10% Pd-C (25 mg) を加え、 水素気流下、 常圧にて 15 時間撹拌した。 反応液を濾過し、 溶媒留去後、 シリカゲルカラムクロマトグラフィ一 （CHC13： MeOH = 10:1 then 5:1) にて精 製し、 7 (18.3 rag, quant.)を得た。
化合物 7 : 無色結晶. mp 239-243 °C (MeOH). [a]o 23+92.2 ° (c = 0.3, Me OH). IR v (KBr)： 3331, 3091, 3059, 2961, 1689, 1463, 1272. 1049 cm"1. !H-NM (CD30D) δ： 3.76, 3.96 (2H, AB, J = 8 Hz), 3.90 (2H, s), 4.04 (1H, s), 4.28 (1H, s), 5.55 (1H, s), 5.69 (1H, d, J = 8 Hz), 7.88 (1H, d. J = 8 Hz).
Anal. Calcd. for d。1^ 2N206 ： C, 46.88; H, 4.72; N, 10.93.
Found: C, 46.74; H. 4.70; N, 10.84. (7) 5'—0—（4, 4' _ジメ トキシトリチル）一 2'— 0, 4'— C—メチレン ゥリジン （8) の合成
化合物 7 (140 mg, 0.53 ramol) に無水ピリジンを加えて 3回共沸した後、 無 水ピリジン溶液 （1.5 ml) とし、 窒素気流下、 室温で 4 , 4 '—ジメ トキシトリチ ルクロリ ド （210 rag, 0.63 隱 ol)、 DMAP (6.5 mg, 0.053 隱 ol)を加え室温 で 5時間撹拌した。 反応溶液に飽和重曹水を加えた後、 CH2C12 で抽出した。 有 機層を水、 飽和食塩水で洗浄後、 無水硫酸ナトリウムにて乾燥した。 溶媒を減圧 留去し、 得られた粗成績体をシリ力ゲル力ラムクロマトグラフィ一（CHC13 ： MeOH = 40:1)により精製し、 化合物 8 (230 mg, 0.34 mmol, 66¾)を得た。
化合物 8 : 白色粉末. mp 117-120 °C (CHC13). [«]D 23+17.2 ° (c = 1.0, CHCU). IR v (KBr): 3393， 3101, 2885, 1689, 1464, 1272， 1047 cm-1.1H-N MR (CDCI3) δ 2.59 (1H, br), 3.56 (2H. q, J = 7. 11 Hz), 3.87 (1H, d， J = 7 Hz), 4.26 (1H, s), 4.47 (1H, s), 5.60 (1H, d, J = 9 Hz), 5.63 (1H, s), 5.84 (4H, d, J = 9 Hz), 7.22-7.45 (9H, ra), 7.93 (1H, d, J = 9 Hz). [実施例 2] ヌクレオシド類縁体の合成
(1) メチル =5— 0— ( t—ブチルジフヱニルシリル） 一4—ヒ ドロキシ
メチル一 2, 3— 0—イソプロピリデン一 /3— D—リボフラノシド (14) の合成
窒素気流下、 文献既知化合物 13 (2.0()8,8.54匪01)の無水じ^12じ 12溶液（40 ml)に氷冷下で Et3N(2.62ral, 18.8mmol)、 tーブチルジフエニルシリノレクロリ ド（4. 88ml， 18.8mmol)を加え、 室温で 13時間撹拌した。 反応溶液に飽和重曹水を加え た後、 AcOEtで 3回抽出した。 有機層を飽和食塩水で 1回洗浄後、 無水 Na2S04に て乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマト グラフィ一 （へキサン： AcOEt=5:l)により精製し、 無色油状物質 14 (2.82g, 5.9 8mmol， 70%)を得た。
[α]ο17-16.2° (c=0.52,CHCl3) IRレ （KBr) :3510, 3061, 2938, 2852, 1465, 110 3cm—
^-NMR (CDC 13) δ ： 1.09(9H,s), 1.28(3H, s), 1.49(3H，s), 3.22(3H, s), 3.67, 3.76(2H, AB, J=llHz), 3.88, 3.93(2H, AB, J=llHz), 4.49(1H, d, J=6Hz), 4.57C1H, d, J=6Hz), 4.93(1H, s), 7.38-7.43C6H, m). 7.67(4H, d， J=7Hz).
13C— NMR (CDC ") 5 c : 19. % 24.4, 25.9, 26.9, 55.0, 62.9, 64.8, 82.2, 85.9, 88.7, 108.6, 112.6, 127.8, 129.9, 133.0, 135.7.
Anal. Calcd for C26H3606Si · 1/4 H20： C, 65.45; H， 7.71. Found :C, 65.43; H, 7.59.
(2) メチル =5—0— ( t—ブチルジフヱニルシリル） 一2, 3—0—
ィソプロピリデン一 4— (p— トルエンスルホニルォキシメチル） —^—リボフラノシド （15) の合成
窒素気流下、 化合物（2.13g,4.51mmol)の無水 CH2C12溶液 （15ml)に室温で Et3N (3.92g, 28.0匪 ol)、p—トルエンスルホニルクロリ ド（1.34g, 7.22ramol)、 4ージメ チルァミノピリジン（90mg, 0.72mmol)を加え、 室温で 17時間撹拌した。 反応溶 液に飽和重曹水を加えた後、 AcOEtで 3回抽出した。 有機層を飽和食塩水で 1回 洗浄後、 無水 Na2S04にて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリ 力ゲルカラムクロマトグラフィ一 （へキサン： AcOEt=10:l)により精製し、 無色 油状物質 15 (2.76g, 4.42隱 ol, 98%)を得た。
[α]ο17-3.82° (c=0.56,CHCl3) IR （KBr) :2934, 2852, 1369, 1104cm-1.
1H— NMR (CDC ") δ ： 1.02(9H,s), 1.20(3H, s), 1.32(3H, s), 2.4K3H, s), 3.09(3H, s), 3.51,3.77(2H. AB, J=10Hz)( 4.34(1H, d, J=6Hz), 4.25, 4.39(2H, AB, J=9Hz), 4.47(1H, d, J=6Hz), 4.77(1H, s), 7.28, 7.8K4H, AB, J=9Hz), 7.39-7. 44(6H,ra), 7.62-7.65(4H, m), 7.8K2H, d, J=9Hz).
13C 匪 R (CDC ") (5 c ： 19.2, 21.6, 24.5, 25.8, 26.8, 54.9, 62.7, 68.8, 81.9, 85.6, 87.5, 108.7. 112.8, 127.7, 127.8, 128.2, 129.6, 129.9, 132.9, 135.6, 144.4.
Anal. Calcd for C33H4208SSi:C, 63.23; H, 6.75;S， 5.11. Found :C, 62.99; H.6.5 3; S, 5.13.
(3) メチル =5— 0— ( t—ブチルジフヱニルシリル） 一 4一 （p— トルエン スルホニルォキシメチル） 一 3— D—リボフラノシド （16) の合成 化合物 15 (645rag, 1.03ramol)の THF- H20[llml, 8:3(v/v)]溶液に室温でトリフロ 口酢酸（14ml)を加え、 室温で 20分撹拌した。 溶媒を減圧留去し、 得られた粗成 績体をシリカゲルカラムクロマ卜グラフィー （hexane:AcOEt=5:l)により精製し、 無色油状物質 16 (464mg, 0.79ramol, 77%)を得た。
[ ] D1 7 - 35.8° (c=1.90,CHCl3) IRレ （KBr) :3499， 3051, 2931. 2840, 1594, 146 8, 1362, 1109cm-1.
'H-N R (CDC 13) δ 1.02(9Η( s), 2.42(3Η, s), 3.16(3Η, s), 3.54. 3.70(2Η, ΑΒ, J=10Hz), 3.97(1Η, d, J=5Hz), 4.18(1Η, d, J=5Hz), 4.26, 4.39(2H, AB, J=10Hz), 4.73C1H, s), 7.30(2H, d, J=8Hz)( 7.36-7.44(6H, m), 7.59-7.66(4H, m), 7.78(2H, d, J=8Hz).
13C-NMR(CDC 13)5c : 19.2, 21.6, 26.7. 55.2, 66.5, 69.6, 74.0, 75.2, 76.5, 84.8, 107.5, 127.7, 128.0, 129.8， 132.6, 132.7. 132.8, 135.5, 135.6, 144.9.
Anal. Calcd for C30H38SSi08'l/4 H20:C, 60.94; H, 6.56. Found :C, 60.94; H, 6.4 3.
(4) メチル =5—0— ( t—ブチルジフエニルシリル） 一2— 0, 4 -C- メチレン一 yS— D—リボフラノシド （17) 及び
メチル =5— 0— （ t—プチルジフエニルシリル） 一3— 0, 4 -C- メチレン一 /3— D—リボフラノシド （18) の合成
窒素気流下、 化合物 16 (194mg,0.33隱 ol)の無水 THF溶液 （4ral)に室温で NaHMDS(3.30匪 ol)の benzene懸濁液 (1.6ml)を加え、 室温で 1時間撹拌した。 反 応溶液に飽和重曹水を加えた後、 反応溶媒を留去し、 AcOEtで 3回抽出した。 有 機層を飽和食塩水で 1回洗浄後、 無水 Na2S04にて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマ卜グラフィ ー （へキサン： Ac0Et=5: 1)により精製し、 無色油状物質 17 (48mg,0.116mmol,35¾ 及び無色油状物質 1 8 (59mg, 0.142raraol, 43¾)を得た。
化合物 17 :IRリ（KBr):3438, 3064, 1103, 1036cm—
1H— NMR (CDC 13) δ ： 1.08(9H,s), 2.04(lH,br s), 3.39(3H, s), 3.65, 3.98(2H, AB, J=8Hz), 3.95, 4.02(2H, AB, J=12Hz), 4.02(lH,s), 4.30(1H, s), 4.79 (lH,s)， 7.38-7.46(6H, m), 7.65-7.69(4H, m).
13C-NMR (CDC 1 3) (5 : 19.2, 26.7, 55.0, 60.7. 71.2, 73.1, 79.9, 85.5, 104.3, 127.8, 129.9. 130.0, 132.9, 135.6, 135.7.
Anal. Calcd for C23Il3005Si'l/4 H20:C.65.68; H, 7.34. Found :C, 65.98; H, 7.23. 化合物 1 8 :IRレ （KBr):3456, 3058, 2938, 2852, 1467, 1108cm-1.
^-NMR (CDC 1 3) δ ： 1.10(9H. s), 3.26C3H, s), 3.71(2H,s), 4.02(1H, d, J=6Hz), 4.35, 4.95(2H, d, J=7Hz), 5. Ol(lH.s), 5.1K1H, d, J=6Hz), 7.38-7.4 4(6H, m), 7.66(4H, d, J=7Hz).
13C-NMR (CDC 1 3) 。 ： 19.3, 26.8, 55.4, 63.7, 75.1, 77.9, 84.5, 86.3， 111.9, 127.8, 128.0, 129.9, 132.9, 133.0, 135.6, 135.8. 135.9. Anal. Calcd for C23H3005Si.l/4 H20:C, 65.91; H, 7.34. Found :C.66.07; H, 7.14. (5) メチル = 3—O—ァセチルー 5—O— ( t—ブチルジフヱ二ルシリ
ル） 一 2— 0, 4— C—メチレン一^一 D—リボフラノシド （ 1 9 ) の合成
窒素気流下、 化合物 1 7 (704mg, 1.70議 ol)の無水ピリジン溶液 （10ml)に室温 で無水酢酸（0.38ml, 4.08關 ol)、 4ージメチルァミノピリジン（21mg, 0.170園 ol)を 加え、 室温で 3時間撹拌した。 反応溶液に飽和重曹水を加えた後、 AcOEtで 3回 抽出した。 有機層を飽和食塩水で 1回洗浄後、 無水 Na2S04にて乾燥した。 溶媒を 減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （へキサ ン ： Ac0Et=7:l)により精製し、 無色油状物質 19 (665mg, 1.46隱 ol,86¾)を得た。
[ ] D17— 34.3° (c=0.93, CHC13) IRレ （KBr):3438, 3064, 2934, 1749, 1468, 110 3, 1036cm一1.
'H-NMR (CD C ") δ ： 0.99(9H,s), 1.97C3H, s), 3.34(3H, s), 3.69.3.8 6(2H, AB, J=8Hz), 3.86(2H, s), 4.17(1H, s), 4.77C1H, s), 5.06(1H, s), 7.28-7.3 9(6H, ra), 7.58-7.63(4H, m).
13C— NMR (CDC 1 3) (5 : 19.3, 20.9, 26.7, 55.0, 60.3, 72.0, 73.6, 78.3, 85.3, 104.4, 127.7. 129.8, 133.0, 135.6, 169.8. Anal. Calcd for C25H3206Si- 1/4 H20:C, 65.12; H, 7.10. Found :C, 65.27;H, 7.00. (6) 5'— 0— (t—プチルジフヱニルシリル） 一2' -0, 4' — C—メチ レン一 5—メチルゥリジン （20) の合成
窒素気流下、 化合物 19 (109.2g.0.239mraol)の無水 CH3CN溶液 （2ml)に室 温で 0, 0'—ビストリメチルシリルチミン（154mg， 0.598mmol)を加えた後、 氷冷 下で卜リメチルシリルトリフルォロメタンスルホネ一卜（0.82ml, 8.74匪 ol)の 1, 1ージクロロェタン（0.31ral)溶液を加え、 室温で 18時間撹拌した。 反応溶液を CH2C 12で希釈し、 飽和重曹水を加えた後、 AcOEtで 3回抽出した。 有機層を 飽和食塩水で 1回洗浄後、 無水 Na2S04にて乾燥した。 溶媒を減圧留去し、 得られ た粗成績体をシリカゲルカラムクロマトグラフィ一 （へキサン： Ac0Et=3:l)によ り精製し、 無色油状物質 20 (87.7mg, 0.173隨 ol' 70¾)を得た。
IRレ （KBr):3048, 2935, 2852. 1749, 1466, 1369, 1234, 1108, 1040cm-1.
1H— NMR (CDC 13) δ 1.06(9H, s), 1.94(3H. s), 2.98(1H, br s), 3.63. 4.00(2H, AB, J=10Hz), 3.72(1H, d, J=7Hz), 3.82-3.84(2H, m), 4.30(1H, s), 5.25 (lH,s), 7.40-7.46(6H, m), 7.60(4H, d, J=6Hz), 7.66(1H. s), 9.68(lH,br s).
[実施例 3] ヌクレオシド類縁体の合成 （別法）
(1) 3— 0—ベンジルー 5— 0— t一ブチルジフヱニルシリル一 4— (ヒ ドロ キシメチル） 一 1, 2— 0—イソプロピリデン一 一 D—エリス口ベント フラノース （32) の合成
窒素気流下、 氷冷下で前記文献 5) に従って調整した化合物 31(2.50 g, 8.0 8 mmol) の塩化メチレン溶液 （50 ml) に、 卜リェチルァミ ン （3.71 ml, 26.6 m raol)、 t-ブチルジフヱニルシリルクロリ ド （6.94 ml, 26.7 mmol) を加え、 室温 で 10.5 時間撹拌した。 反応溶液に飽和重曹水を加えた後、 酢酸ェチルで抽出し た。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムで乾燥した。 溶媒を減圧留去 し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （AcOEt-へキサン， 1:4 → 1:3) により精製し、 白色固体 （32) (2.97 g, 5.41 mmol, 67 ¾) を 得た。
mp. 98 - 99 °C (へキサン） . [a] D 20 + 54.8 ° (c = 1.12. アセトン）. IR レ max (Or) ： 3553, 2936. 1463, 1379, 1107 cm 1. 'H-N R (CDC13) δ： 1.13 (9Η, s), 1.50 (3H, s), 1.78 (3H, s)， 2.56 (1H, t, J = 7 Hz), 3.82, 3.92 (2H, AB, J = 11 Hz), 3.94 (2H, t, J = 6 Hz), 4.57 (1H, d. J = 5 Hz), 4. 64, 4.95 (2H, AB, J = 12 Hz), 4.83 (III, dd, J = 4, 5 Hz), 5.95 (1H， d, J = 4 Hz), 7.44-7.55 (11H, m), 7.72-7.78 (4H, ra). 13C-讓 (CDC13) < 19. 2, 26.2, 26.5, 26.8, 63.2, 65.4, 72.5, 77.9, 79.1, 87.4, 104.4, 113.7. 1 27.6, 127.7, 128.0, 128.5, 129.5, 129.7, 132.9, 133.1, 134.7, 135.5, 137. 2.
Anal. Calcd for C32H4006Si ： C, 70.04; H, 7.38. Found ： C, 70.19; H, 7.3 5.
(2) 3—0—ベンジル一 5—O— ( t _プチルジフエ二ルンリル） 一4— (p — トルエンスルホニルォキシメチル） 一 1, 2— <¾— D—エリス口ベント フラノース （33) の合成
窒素気流下、 氷冷下で 32(250 mg, 0.456 mmol) の塩化メチレン溶液に、 ト リエチルアミ ン （395 ρΛ, 2.83 mmol), p-トルエンスルホニルクロリ ド （139.2 mg, 0.730 mmol) 及び 4 -ジメチルアミノピリジン （8.92 mg, 0.0730 mmol) を 加え、 室温で 15.5 時間撹拌した。 反応溶液に飽和重曹水を加えた後、 酢酸ェチ ルで抽出した。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて乾燥した。 溶 媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （Ac OEt-へキサン， 1:6) により精製し、 淡黄色油状物質 （33) (310.6 mg, 0.442 mmol, 97 ¾) を得た。
[ ] D20 + 16.0 ° (c = 0.44, アセトン）. IR max (KBr) ： 2935, 1595, 146
2, 1363. 1174. 1106 cm"1. ^-NMR (CDC13) δ： 1.08 (9Η, s), 1.40 (3H, s), 1.46 (3H, s). 2.48 (3H, s), 3.68, 3.83 (2H, AB, J = 11 Hz) ， 4.45 (2H, dd, J = 4. 5 Hz), 4.64, 4.81 (2H, AB, J = 12 Hz), 4.68 (1H, dd, J = 4, 5 Hz), 5.81 (1H, d, J = 4 Hz), 7.32 (2H, d, J = 8 Hz). 7.42-7.72 (15H， m), 7.82, (2H, d， J = 8 Hz), 7.66 (4H, m), 7.72 (2H, d, J = 8 Hz). 13C-讀 (CDC13) 5c: 19.1, 21.5, 26.1, 26.4. 26.7, 64. , 70.0, 72.5. 78.1, 78.9, 85.4, 104.2, 113.6, 127.3, 127.7, 127.9, 128.0, 128.4. 129.6. 129.7. 12 9.8, 132.7, 132.8, 135.5, 137.2, 144.4. MS (EI) m/z ： 646 ( +-t-Bu). Hi gh-HS (EI) ： Calcd for C35H3708SSi (M+-t-Bu) ： 645.1978. Found ： 645.19
69.
(3) 1, 2—ジ一 O—ァセチル一 3—0—ベンジルー 5—0— t—ブチルジ フエニルシリル一4_ (p—トルエンスルホニルォキシメチル） — α— および一 ;9— D—リボフラノース （34) の合成
窒素気流下、 34 (3.70 g, 5.27 mmol) の酢酸溶液 （56 ml) に無水酢酸 （6. 0 ml, 63.6 mmol) 及び濃硫酸 （56 jul, 1.10 mol) を加え、 室温で 2 時間撹 拌した。 反応溶液を氷水 （300 ml) にあけて 30 分間撹拌した後、 飽和食塩水を 加え、 酢酸ェチルで抽出した後、 有機層を硫酸マグネシウムにて乾燥した。 溶媒 を留去して得られた粗成績体をシリカゲルカラムクロマトグラフィー （AcOEt-へ キサン， 2:1) により精製し、 黄色油状物質 （34) (3.36 g, 4.53 匪 ol, 86 ¾) を α ： ;3 = 1:4 の混合物として得た。
IR レ max (KBr) ： 2934, 2863, 1751. 1365, 1217, 1106 cm"1. 'H-NMR (CDC13) [/3体] δ： 1.02 (9H( s), 1.77 (3H, s), 1.98 (3H, s), 2.39 (3H, s), 3.61, 3.76 (2H, AB, J = 11 Hz), 4.21-4.58 (5H, m), 5.26 (1H, d, J = 5 Hz). 5. 94 (1H, s), 7.15-7.59 (13H, in), 7.58-7.66 (4H, ra), 7.72 (2H, d, J = 8 Hz) . [ 体] d: 1.02 (9H, s), 1.98 (3H, s), 2.36 (3H, s), 3.48. 3.58 (2H, AB, J = 11 Hz), 4.21-4.58 (5H, m)， 5.12 (1H, dd, J = 5, 6 Hz), 6.33 (1H, d, J = 5 Hz), 7.15-7.59 (13H, m), 7.58-7.66 (4H, m), 7.72 (2H. d, J = 8 Hz) • 13C -腿 (CDC13) ( c : 14.2, 19.3, 20.5, 20.8, 21.6, 26.7, 26.8, 60.3, 6 4.8, 69.1, 73.6, 74.1, 78.6, 85.3, 97.4, 127.4, 127.6, 127.7, 127.8, 127. 9, 128.0, 128.2, 128.3, 128.4, 129.5, 129.6, 1289.8. 129.9, 132.4, 132.8, 132.9, 135.4, 135.5, 135.6. 136.9, 144.5, 168.7， 169.4. High-MS(FAB) ： Calcd for 。！ 0SSiNa (M++Na) ： 769.2479, Found ： 769.2484.
(4) 2' —0—ァセチル一 3' —0—ベンジル一 5' — 0— t—ブチルジフエ ニルシリルー 4' — P— トルエンスルホニルォキシメチル一 5—メチルゥ リジン （35) の合成
窒素気流下、 氷冷下で 34(L88g, 2.52 mraol) の 1, 2-ジクロロエタン溶液 (26 ml) に 2TMS.T (1.04 g, 4.03議 ol) 及びトリメチルシリルトリフルォロメ タンスルホナート （730 β\, 4.03 ramol) を加え、 室温で 17 時間撹拌した。 反 応溶液に飽和重曹水を加え、 セライ 卜濾過した後、 母液をクロ口ホルムで抽出し た。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて乾燥した。 溶媒を減圧留 去して得られた粗成績体をシリカゲルカラムクロマトグラフィー （AcOEt-へキサ ン， 2:3) により精製し、 白色粉末 （35) (2.00 g, 2.44 mmol, 97 ) を得た。 mp. 70 - 71.5 °C. C«] D24 + 4.58 ° (c = 1.25, アセトン）. IR レ max (KBr) ： 3059, 2934, 1694, 1465， 1368, 704 cm-1. -匿 (CDC13) δ 1.18 (9Η, s) , 1.63 (3H, d, J = 1 Hz), 2.10 (3H, s) , 2.42 (3H, s) , 3.73, 3.86 (2H, AB, J = 11 Hz), 4.12, 4.20 (2H, AB, J = 11 Hz), 4.44, 4.57 (2H, AB, J = 11 Hz) , 4.45 (1H, d, J = 6 Hz), 5.38 (1H, t, J = 6 Hz), 6.02 (1H, d, J = 6 Hz), 7.21-7.60 (13H， m), 7.62-7.69 (7H, m), 8.91 (1H, br s). 13C -賺 (CDCI3) δ 11.9, 19.3. 20.6, 21.6, 27.0, 65.3, 68.6, 74.1. 74.8, 77.2, 77.3, 86.0, 86.4, 111.6, 127.9, 128.0, 128.2, 128.5, 129.7, 130.1. 130. 2, 131.8, 132.3, 132.5, 135.3, 135.5, 135.6. 136.8, 144.9, 150.2, 163.4, 170.2. MS (FAB) m/z ： 813 (M++H).
Anal. Calcd for C43H48 2O10SSi-2H20: C, 60.83; H, 6.17; N, 3.30. Found ： C, 60.55; H, 5.78; N, 3.22.
(5) 3' —0—ベンジルー 5' —O— t—ブチルジフヱニルシリル一 4' - p —トルエンスルホニルォキシメチル一 5—メチルゥリジン （36) の合成 氷冷下、 35 (250 mg, 0.308 mmol) のメチルアルコール溶液 （4 ml) に炭酸 カリウム （12.75 rag, 0.0923 mmol) 及び水 （0.5 ml) を加え、 室温で 22 時間 撹拌した。 氷冷下、 反応溶液に酢酸を加えて中和した後、 溶媒を減圧留去した。 残渣に水を加えた後、 酢酸ェチルで抽出した。 有機層を飽和食塩水で洗浄した後、 硫酸ナトリウムで乾燥した。 溶媒を減圧留去した後、 得られた粗成績体をシリカ ゲルカラムクロマトグラフィー （AcOEt-へキサン， 3:2) により精製し、 白色粉 末 （36) (216.7 rag, 0.283 mmol, 92 ¾) を得た。
rap. 74 ― 77 °C. [ ] D 23 + 5.15 ° (c = 1.23, CHC13). IR レ max (KBr) ： 30 48, 2934, 1695, 1363, 1181, 1108. 977, 819, 704 cm- 1. 1H-NMR (CDC13) d: 1.05 (9H, s), 1.65 (3H, d, J = 1 Hz), 2.39 (3H， s), 3.04 (1H, br d, J = 9 Hz), 3.72 (2H, s), 4.17 (2H, s), 4.18 (1H, d, J = 5 Hz), 4.24-4.32 (1H, m), 4.54, 4.62 (2H, AB, J = 11 Hz), 5.62 (1H, d, J = 6 Hz), 7.19-7.69 (20H, ra), 8.46 (1H, br s). 13C-NMR (CDC13) δ 12.1, 19.4. 26.9, 58.8. 7 2.0, 72.2. 75.8, 76.7, 87.4, 88.8, 110.4, 127.7, 12.79, 128.1, 128.2, 12 8.5, 128.7, 129.8, 130.0, 130.1, 132.2, 134.3, 135.3, 135.5, 136.8, 149. 8, 163.9. MS (FAB) m/z ： 771 (M++H).
Anal. Calcd for C41H46N209SSi: C, 63.41; H, 6.16; N, 3.51; S, 3.95.
Found ： C, 63.87; H, 6.01; N, 3.63; S, 4.16.
(6) 3' —O—ベンジルー 5' —O— tーブチルジフエニルシリル一 2' — 0, 4' —C—メチレン一 5—メチルゥリ ジン （37) の合成
窒素気流下、 氷冷下で 36 (1.86 g, 2.42 mraol) のテトラヒ ドロフラン溶液 (30 ml) にナトリウムビス （卜リメチルシリル） アミ ド （1.0 M in THF, 8.47 m 1, 8.47 mmol) を加え、 室温で 1 時間撹拌した。 反応溶液に飽和重曹水 （14 ml) を加えた後、 溶媒を減圧留去した。 残渣に水を加え、 クロ口ホルムで抽出した。 有機層を飽和食塩水で洗浄した後、 硫酸ナトリウムにて乾燥した。 溶媒を減圧留 去し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （AcOEt-へキサ ン， 2:3) により精製し、 白色粉末 （37) (1.42 g, 2.37 mmol, 98 ¾) を得た。 mp. 70.5- 72 °C. [ ] D 22 + 52.47 ° (c = 1.025， ァセトン）. IR リ max (KBr) ： 2936, 1694, 1465, 1275, 1106, 1055, 809. 704 cm-1. ^- HR (CDC13) δ : 1.21 (9H, s). 1.76 (3H, s), 3.88， 4.07 (2H, AB, J = 8 Hz), 4.07, 4.15 (2H, AB, J = 11 Hz), 4.16 (1H, s), 4.66, 4.80 (2H, AB, J = 11 Hz), 4.76 (1H, s), 7.34-7.79 (16H, ra), 10.0 (1H, br s). MS (FAB) m/z ： 599 (M++H). Anal. Calcd for C34H38N20eSi'2H20: C, 64.33; H, 6.03; N, 4.41. Found ： C, 64.58; H, 6.15; N, 4.28.
(7) 3' —0—ベンジル一 2' -0, 4' —C—メチレン一 5—メチルゥリジ ン （38) の合成
窒素気流下、 37 (188.7 mg, 0.316mmol) のテトラヒ ドロフラン溶液 （1 ml) に、 テトラプチルアンモニゥムフルオリ ド （1.0 M in THF, 379 βΐ, 0.379 ra ol) を加え、 室温で 2.5 時間撹拌した。 反応溶液を減圧留去して得られた粗成 績体をシリカゲルカラムクロマトグラフィー （AcOEt-へキサン， 1:1→1:0) によ り精製し、 白色粉末 （38) (94.6 mg, 0.262隨 ol, 83 %) を得た。
IR max (KBr) ： 3424, 3183, 3063, 2950, 1691, 1463, 1273, 1057, 734cm-1. •H-NMR (CDC13) δ： 1.90 (3Η, d, J = 1 Hz), 3.83, 4.05 (2H. AB, J = 8 Hz) ， 3.93, 4.02 (2H， AB, J = 12 Hz), 3.94 (1H, s)， 4.53 (1H, s), 4.56, 4.58 (2H, AB, J = 12 Hz), 5.65 (1H, s), 7.32 (5H, s), 7.44 (1H, d， J = 1 Hz). High - MS (EI) ：
Calcd for C18H20N06 (M+) ： 360.1321, Found ： 360.1312. (8) 2'— 0. 4' —C—メチレン一 5—メチレンゥリジン （39 a) の合成 化合物 38 (86.5 mg, 0.240 mraol) のメチルアルコール溶液 （4 ml) に 20 % Pd(0H)2-C (86.5 mg) を加え、 水素気流下常圧にて 14.5 時間撹拌した。 反応溶 液を濾過した後、 溶媒を減圧留去して無色結晶 （39) (62.5 mg, 0.230 mmol, 96 ¾) を得た。
nip. 194- 195 °C. [a] D 20 + 53.7 ° (c =1.02, EtOH). IR レ max (KBr) ： 332 3, 3163, 3027, 2889, 2826, 1689, 1471. 1276, 1057 cm— 1. »H-NMR (CD30D) δ： 1.89 (3H, q, J = 1 Hz), 3.74, 3.95 (2H, AB, J = 8 Hz), 3.90 (1H, s),
4.07 (1H, s), 4.26 (1H, s), 5.53 (1H, s) , 7.74 (1H, d, J = 1 Hz). 13C - 隱 (CD30D) dc: 12.6, 57.6, 70.3, 72.4, 80.8, 88.3， 90.4, 110.7, 136.8,
151.8, 166.5.
[実施例 4 ]
(1) 2' — O—ァセチルー 3' —O—ベンジル一 5' — O— t—ブチルジフエ ニルシリル一 4' — p— トルエンスルホニルォキンメチル一Νβ —べンゾ ィルアデノシン （40) の合成
文献 6) (H. Vorbrggen, K. Krolikiewicz and B. Bennua, Chem. , Ber. , 114, 1234-1255 (1981)) に従って調整した 2TMS-ABz (128.7 rag. 0.336 mmol) に窒 素気流下、 室温で 34 (250 mg, 0.336 mmol) の 1, 2-ジクロロエタン溶液 （5.0 ml) 及び卜リメチルシリルトリフルォロメタンスルホナー ト （6.7〃 1, 0.0336 mmol) を加え、 26 時間加熱還流した。 反応溶液に飽和重曹水を加えた後、 塩化 メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて 乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグ ラフィー （CHC13- MeOH. 30:1) により精製し、 白色粉末 （40) (234.5 mg, 0. 253 mmol, 75 ¾) を得た。
mp. 77-78 。C (AcOEt / へキサン）. [な] D 24 _ 13.2 ° (c = 1.00. CHC13). IR umax (KBr) ： 3058, 2934, 1749, 1703. 1606, 1105 cnr1. 'H-NM (CDC13) 6 : 0.99 (9H, s). 2.04 (3H, s), 2.38 (3H, s), 3.74, 3.85 (2Π, AB, J = 1 1 Hz), 4.31, 4.43 (2H, AB, J = 11 Hz), 4.52. 4.58 (2H, AB, J = 11 Hz) , 4.81 (1H, d, J = 6 Hz), 5.94 (10, d, J = 6 Hz), 6.04 (1H, d, J = 5 Hz), 7.18 一 7.61 (20H, m), 7.69 (2H, d, J = 8 Hz), 7.99 (1H, s), 8.01 (2H. d, J = 7 Hz), 8.56 (1H, s), 8.99 (1H, br s). 13C-隱 (CDC13) <5c: 19.1, 20. 5， 21.5, 26.7, 64.1, 68.4, 74.0, 74.6. 77.9, 86.57, 86.64, 123.4, 127.7, 127.8, 127.9, 128.1, 128.5, 128.8， 129.6, 129.9, 132.0. 132.3, 132.6, 1 32.7, 133.5, 135.4, 135.5, 136.8, 142.0, 144.7, 149.6, 151.2, 152.6, 164. 5, 169.8. MS (FAB) m/z ： 926 (M++H) .
(2) 3' —O—べンジルー 5' — O— t—ブチルジフヱニルシリル一 4' - p —トルエンスルホニルォキシメチル一Νβ —ベンゾィルアデノシン （41) の合成
化合物 40(167.9 mg, 0.182 mmol) のメチルアルコール溶液 （3.0 ml) に室 温で炭酸カリウム （15.0 mg, 0.109 mmol) を加えた後、 室温で 15 分撹拌した。 反応溶液に濃塩酸を加えて溶液を中和した後、 塩化メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （CHCl3-MeOH, 30:1) により精製し、 白色粉末 （41) (140.5 mg, 0.160 mmol, 88 ¾) を得た。
mp. 82- 83 °C (AcOEt—へキサン）. [a] D 25 — 6.02 。 （c = 0.96, CHC13). IB リ max (KBr) ： 3306, 3066. 2935. 2859, 1701. 1611 cm 1. ^- HR (CDC13) δ : 0.98 (9H, s), 2.37 (3H, s), 3.76 (2H, s), 4.39, 4.45 (1H, AB, J = 11 Hz), 4.54 (1H, d, J = 6 Hz), 4.67, 4.76 (2H， AB, J = 11 Hz), 4.85 (1H, dd, J = 5, 6 Hz), 5.79 (1H, d, J = 5 Hz), 7.20 - 7.58 (21H, m), 7.73 (2H, d， J = 8 Hz), 7.80 (1H, s)， 7.96 (2H, d, J = 8 Hz), 8.49 (1H, s), 9.18
(1H, br s). 13C-NME (CDC13) 5c: 19.1, 21.6. 26.8. 64.4. 68.9, 74.1, 74.
6， 79.2, 86.8, 89.8. 123.1, 127.7, 127.8, 128.0, 128.2. 128.4. 128.6. 12 8.8, 129.7, 130.0, 132.1, 132.5, 132.6, 132.8, 133.4, 135.4. 135.5, 136.
8, 142.1, 144.8, 149.4, 152.3, 164.5.
(3) 3' —O—ベンジル一 5' —O— t—ブチルジフエニルシリル一 2' — 0， 4' — C—メチレン一 Νβ —ベンジルアデノシン （42) の合成 窒素気流下、 41(210.5 mg, 0.238 mmol) のテトラヒ ドロフラン溶液 （8· 0 m 1) に室温でナトリウムビス （トリメチルシリル） ァミ ド （1.0 M in THF, 0.58 ml, 0.572 mmol) を加えた後、 室温で 3 時間撹拌した。 反応溶液に飽和重曹水 を加えた後、 塩化メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫 酸ナトリウムにて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲル カラムクロマトグラフィー （CHC13- MeOH, 30:1) により精製し、 白色粉末 （42) (169.5 rag, 0.238 mmol, quant. ) を得た。
mp. 80- 81 °C. IR レ max (KBr) ： 3259, 3064, 2932, 2858. 1703, 1607 cm"1. Ή-NMR (CDC13) δ ： 1.07 (9H, s), 3.95, 4.10 (2H, AB, J = 8 Hz), 4.02 (2 H， d， J = 8 Hz), 4.56, 4.64 (2H, AB, J = 12 Hz), 4.26 (1H， s) , 4.86 (1H, s), 6.14 (1H, s), 7.26 ― 7.70 (18H, m), 8.04 (2H, d, J = 7 Hz), 8.22 (1 H, s), 8.78 (1H, s), 9.18 (1H, br s). 13C-NMR (CDC13) (5c: 19.2, 26.5, 2 6.8, 29.7, 59.2, 72.4, 72.6. 76.5, 76.8, 86.7, 88.6, 123.4, 127.7, 127.8. 127.9, 128.1, 128.4, 128.8, 129.5, 130.0， 132.4, 132.5, 132.8. 133.5, 1 34.8, 135.2, 135.5, 135.6, 136.8. 140.4, 152.7.
(4) 3' —O—ベンジル一 2' -O, 4' — C—メチレン一 N6 —ベンゾィル アデノシン （43) の合成
化合物 42 (173.6 mg, 0.244 mmol) のテトラヒ ドロフラン溶液 （7.0 ml) に 室温でテトラプチルアンモニゥムフルオリ ド （1.0 M in THF, 1.0 ml, 1.0 mmol) を加え、 室温で 25 分撹拌した。 反応溶液を減圧留去して得られた粗成績体を シリカゲルカラムクロマトグラフィー （CHC13- MeOH, 15:1) により精製し、 白色 粉末 （43) (115.4 mg, 0.244 mmol, quant. ) を得た。
mp. 154 一 155 °C (Et20). IR レ max (KBr) ： 3339, 2944, 1701, 1611 cm—1. 1 H-NMR (CDCI3) δ： 3.91, 4.13 (2H, AB, J = 8 Hz), 3.93, 4.01 (2H, AB, J = 12 Hz), 4.38 (1H, s), 4.64 (1H, s), 4.85 (1H, s), 6.08 (1H, s), 7.29 (1 H, s), 7.51 (2H, d, J = 8 Hz), 7.58 (1H, d, J = 7 Hz), 8.05 (2H, d, J = 7 Hz), 8.14 (1H, s), 8.75 (1H， s), 9.50 (1H, br s). 13C-NMR (CDC13) δ c: 57.1, 2.4, 77.0, 77.1, 86.9, 88.6, 122.9, 127.6, 128.0, 128.1, 128.4. 128.7, 132.8, 133.5, 136.9. 140.5, 149.8, 150.5, 152.8, 165.0.
[実施例 5]
(1) 2' —0—ァセチル一 3' — 0—ベンジル一 5' — 0— t—ブチルジフエ ニルシリル一 4' — p— トルエンスルホニルォキシメチル一 N2 —イソブ チリルグアノシン （44) の合成
前記の文献 6) に従って調整した 3TMS* Gi Bu (146.8 rag, 0.336 mmol) に窒 素気流下、 室温で 4 (250 mg, 0.336 mraol) の 1, 2-ジクロロェタン溶液 （5.0 ml) 及びトリメチルシリルトリフルォロメタンスルホナート （6.7 βΐ, 0.0336 mmol) を加え、 15 時間加熱還流した。 反応溶液に飽和重曹水を加えた後、 塩化 メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて 乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグ ラフィー （CHCl3-MeOH, 30:1) により精製し、 白色粉末 （44) (213.6 mg, 0.2 35 mmol, 70 ¾) を得た。
mp. 96一 97 °C (AcOEt—へキサン）. [a] D 24 -11.09 。 (c = 0.97, CHC13). I R ymax (KBr) ： 3152. 3065, 2934, 1746, 1681, 1606 cm— Ή-NMR (CDC13) d: 0.96 (9H, s), 1.10 (3H, d, J = 9 Hz), 1.13 (3H, d, J = 9 Hz), 1.98 (3H, s), 2.36 (3H, s), 2.48 (1H, m), 3.65, 3.72 (2H, AB, J = 11 Hz), 4.2 3, 4.43 (2H, AB, J = 11 Hz), 4.47 (2H, s), 4.63 (1H, d, J = 6 Hz), 5.74 (1H, t, J = 6 Hz), 5.96 (1H, d, J = 6 Hz), 7.14 ― 7.68 (20H, m), 9.15 (1 H, s)， 12.20 (1H, s). 13C-NMR (CDC13) (5c: 19.1, 19.3, 19.4. 20.8， 21.9, 27.0, 27.2, 36.5, 64.5, 68.9, 74.4, 74.9. 76.7, 86.1, 86.7, 122.0. 127. 6, 127.7, 127.9, 128.1, 128.3, 128.4, 128.8, 130.1, 130.4, 132.3, 132.7, 132.9, 135.7, 135.8, 137.3. 137.8, 145.2, 147.8, 148.5, 156.2, 170.2， 1 78.8.
(2) 3' — O—ベンジルー 5' —O— t—プチルジフエニルシリル一 4' - p ― トルエンスルホニルォキシメチル一 N2 —ィソブチリルグアノシン (45) の合成
化合物 44 (137.0 mg, 0.151 mmol) のメチルアルコール溶液 （3.0 ml) に室 温で炭酸カリウム （15.8 mg, 0.113 ramol) を加えた後、 室温で 45 分撹拌した。 反応溶液に濃塩酸を加えて溶液を中和した後、 塩化メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫酸ナトリウムにて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマトグラフィー （CHC13- MeOH, 30:1) により精製し、 白色粉末 45 (83.4 mg, 0.097 mmol, 64 %) を得た。
mp. 102 一 103 。C (AcOEt—へキサン）. [a] D 25 - 2.00 ° (c = 0.40, CHC13). IR レ max (KBr) ： 3166, 2932, 1684, 1607 cm— 1. !H-NMR (CDC13) δ： 0.90 (9H, s), 1.09 (3H, d, J = 7 Hz), 1.13 (3H, d, J = 7 Hz). 2.30 (1H, m), 2. 37 (3H, s), 3.71, 3.76 (2H, AB, J = 11 Hz), 4.32, 4.48 (2H, AB, J = 11 H z), 4.35 (1H, d， J = 6 Hz), 4.63, 4.90 (2H, AB, J = 12 Hz), 4.96 (1H, t， J = 6 Hz), 5.67 (1H, d, J = 7 Hz), 7.17 ― 7.71 (20H, m), 8.82 (1H, s)， 12.05 (1H, br s).13C-N R (CDC13) <5c: 18.7, 19.0, 21.6, 26.5, 36.2. 63.5, 69.1, 73.7, 74.3, 78.8. 86.2, 89.5, 127.7, 127.8, 128.0, 128.1, 128.5, 129.7, 130.0, 132.0, 132.6, 132.7, 135.3. 135.4, 137.4, 138.2, 144.8, 14 6.9, 155.5, 178.5.
(3) 3' —0—ベンジルー 5' — 0— t—ブチルジフエニルシリル一 2' — 0, 4' — C—メチレン一 N2 —イソプチリルグアノシン （46) の合成 窒素気流下、 45 (92.1 mg, 0.102 mmol) のテトラヒドロフラン溶液 （3.0 m 1) に室温でナトリウムビス （トリメチルシリル） ァミ ド （1.0 M in THF, 0.31 ml, 0.315 mmol) を加えた後、 室温で 3 時間撹拌した。 反応溶液に飽和重曹水 を加えた後、 塩化メチレンで 3 回抽出した。 有機層を飽和食塩水で洗浄後、 硫 酸ナトリウムにて乾燥した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲル カラムクロマトグラフィー （CHC13- MeOH, 25:1) により精製し、 白色粉末 （46) (31.4 mg, 0.160 mmol, 44 %) を得た。
mp. 99 - 100 °C. IR max (KBr) ： 3162, 3068, 2932, 1683, 1610 cm"1. Ή- 隱 (CDC13) δ： 1.06 (9Η, s), 1.25 (3H, d, J = 7 Hz), 1.27 (3H, d, J = 7 Hz), 2.64 (1H, m), 3.83, 4.01 (2H, AB, J = 8 Hz). 3.97 (2H， d, J = 7 H z), 4.18 (1H， s)， 4.51 (1H, s), 4.54 (2H, d, J = 2 Hz), 5.77 (1H, s), 7. 17-7.42 (5H, πθ, 7.64 - 7.72 (雇, m), 7.84 (1H, s). 9.03 (1H, s), 12.08 (1H, br s). 13C-NMR (CDC13) <5c: 18.9, 19.0. 19.1, 26.5, 26.7. 36.4, 59. 1. 72.4, 72.5, 76.8, 77.5, 86.3, 88.3, 121.7, 127.6. 127.7， 127.8, 127.9, 128.1. 128.4, 129.6, 130.0, 132.36, 132.42, 134.8, 135.45, 135.54, 135.
8, 136.8. 146.8, 147.7, 155.4, 178.6.
(4) 3' —0—ベンジル 1—2' -0, 4' — C—メチレン一 N2 —イソプチ
リルグアノシン （47) の合成
化合物 46 (41.3 nig, 0.060 mmol) のテトラヒ ドロフラン溶液 （3.0 ml) に 室温でテトラプチルアンモニゥムフルオリ ド （1.0 M in THF, 0.90 ml, 0.90 mm ol) を加えた後、 室温で 1 時間撹拌した。 反応溶液を減圧留去して得られた粗 成績体をシリカゲルカラムクロマトグラフィー （AcOH- EtOH, 20:1) により精製 し、 白色粉末 （47) (27.1 mg, 0.060 mmol, quant. ) を得た。
mp. 228 - 229 °C (Et20). [a] D25 + 32.90 。 （c = 0.875. CHC13). IR max (KBr) ： 3162, 2934, 1683, 1608 cm"1. Ή-NMR (CDC") δ： 1.24 (3H. d, J = 7 Hz), 1.26 (3H, d, J = 7 Hz), 2.76 (1H， m), 3.83, 4.03 (2H, AB, J = 8 Hz), 3.92. 4.02 (2H, AB, J = 13 Hz), 4.33 (1H, s), 4.55 (1H, s), 4.62 (2H, s), 5.80 (1H, s). 7.25 (5H. s), 7.91 (1H, s), 9.85 (1H, s), 12.05 (1H, s). 13C-薩 (CDC13) (5c: 19.19, 19.25, 36.4, 57.4, 72.5, 77.0, 77.5. 86.5, 88.8, 121.0, 127.8, 128.1, 128.2. 128.3, 128.4, 128.6, 137.1, 137. 5, 147.5, 148.2, 155.7, 179.9.
[実施例 6] オリゴヌクレオチド類縁体の合成
天; »ヌクレオシド
アミダイト
«■«オリゴヌクレオチド ¾ΒΛ*
Figure imgf000034_0001
21
Figure imgf000035_0001
(1) 3'—0— [2—シァノエ卜キシ （ジイソプロピルァミノ） ホスフイノ]— 5'— 0— (4, 4'—ジメ トキシトリチル）一 2'— 0, 4'—メタノ
ゥリジン （21) の合成
化合物 8 (200 mg, 0.31 mmol)、 ジイソプロピルアンモニゥム テトラゾリ ド （39.6 mg, 0.23 mmol)を無水 CH3CN で 3回共沸した後、 無水 CH3CN - 無水 THF溶液 （3:1, 4 ml)とし、 窒素気流下 2—シァノエチル N, N, N' , N'—テトラ イソプロピル ホスホロジアミダイ ト （0.12 ml, 0.37 ramol)を加え、 室温で 90 分間撹拌した。 溶媒を減圧留去し、 得られた粗成績体をシリカゲルカラムクロマ トグラフィー （AcOEt：へキサン： Et3N = 75:25:1) により精製後、 AcOEt-へキ サンにて再沈澱し、 アミダイ 卜体 21 (181 mg. 0.25 mmol, 81¾) を得た。
mp71- 74。C (AcOEt-へキサン）. 31P-隱 (CDC13): δ 149.6, 149.5, 149.4, 149.3. 149.2.
(2) オリゴヌクレオチド類縁体の一般合成 ォリゴマーの合成は Pharmacia社 製 DN A合成装置 Gene Assembler Plusにより 0.2 ； amolスケールで行った。 溶 媒、 試薬、 ホスホロアミダイ トの濃度は天然 DNA合成の場合と同じである。 3' -水酸基が CPG支持体に結合した 5'-0— DMTr-チミジン （0.2 zmol) の DMT r 基をトリクロロ酢酸によって脱保護し、 その 5'-水酸基に天然 DNA合成用の 4 種の核酸塩基からなるアミダイ トおよび化合物 21を用いて縮合反応を繰り返し 行い、 それぞれの配列のオリゴヌクレオチド類縁体を合成した。 合成サイクルは 下記の通りである。
合成サイクル （0.2 ^mol scale)
1) detritylation 1% CC13C00H in CH2C1CH2C1( 6 sec
2) coupling 0.1 phosphoramidite (25 equiv. ), 0.5 M lH-tetrazole (500 equiv. ) in MeCN, 2 min
3) capping 3% 4-(dimethylaraino)pyridine, 10¾ Ac20,
in MeCN, 18 sec
4) oxidation 0.01 M I2 in 2, 4, 6-collidine/H20/MeCN(l:5:ll),
6 sec
合成後は、 常法に従って、 濃アンモニア水処理によりオリゴマーを支持体から 切り出すとともに、 リン原子上の保護基シァノエチル基をはずし、 さらにはアデ ニン、 グァニン、 シトシンの保護基をはずした。
得られた 5' — 0— DMT r化されたオリゴヌクレオチド類縁体は、 逆相カラ ムクロマト （Millipore, Oligo-Pak™ SP) 上でトリフルォロ酢酸 5 m 1により DMT r基をはずし、 引き続き精製を行い、 目的のオリゴヌクレオチド類縁体を 得た。
本一般合成法に従って、 以下のォリゴヌクレオチド類縁体を合成した。
(2) 5' - GCGXTTTTTGCT - 3' (XT5)
収量 0.06 mol (30¾ yield)
(3) 5 GCGTTXTTTGCT - 3' (T 2 XT3)
収量 0.05 〃mol (25¾ yield)
(4) 5 GCGTTTXTTGCT- 3' (T3 XT2)
収量 0.03 1 (15% yield)
(5) 5' 一 GCGTTTTTXGCT - 3' (T 5 X)
収量 0.06 fiml (30% yield)
(6) 5' GCGXXTTTTGCT - 3' (X2T4)
収量 0.06 βαοΐ (30¾ yield)
(7) 5' GCGTTXXTTGCT- 3' (T 2 X 2T 2)
収量 0.05 raol (25% yield)
(8) 5' GCGTTTTXXGCT - 3' (T4 X 2)
収量 0.06 〃mol (30¾ yield)
(9) 5' GCGXXXXXXGCT- 3' (X 6) 収量 0.06 raol (30¾ yield)
(10) 5' - GTTTTTTTTTXXC - 3' (X 2) 収量 0.07 ϊϋοΐ (35¾ yield)
[実験例 1] 融解温度 （Tm) の測定
実施例 2で合成した種々のオリゴヌクレオチド類縁体をアンチセンス鎖とし、 天然の DN Aあるいは RN Aからなるセンス鎖とをァニーリング処理したものの 融解温度 （Tm値） を測定することにより、 本発明のオリゴヌクレオチド類縁体 の相補 DN Aおよび RN Aに対するハイプリッ ド形成能を調べた。
終濃度をそれぞれ、 N a C 1 10 Om . リン酸ナトリウム緩衝液 （ p H 7. 2) 1 OmM、 アンチセンス鎖 4〃M、 センス鎖 4 /Mとしたサンプル溶液 （5 Ο Ο βΙ) を沸騰水中に浴し、 10時間をかけてゆっく り室温まで冷却した。 分 光光度計 （島津 UV-2100PC) のセル室内に結露防止のために窒素気流を通し、 サ ンプル溶液を 5°Cまで徐々に冷却し、 さらに 20分間 5°Cに保った後、 測定を開 始した。 サンプル温度は 90°Cまで毎分 0.2°Cずつ上昇させ、 0. 1°C間隔で 2 60 nmにおける紫外線吸収を測定した。 なお、 温度上昇とともにサンプル濃度 が変化するのを防ぐため、 セルは蓋付きのものを用い、 サンプル溶液表面に鉱油 を 1滴添加して測定した。
結果は、 下記の表に示した。 アンチセンスオリゴヌクレオチド類縁体の相補 DNA及び RNAに対する 融解温度 （Tm値） アンチセンス分子 相補 DNAa>との Tm 相補 RNAb>との Tm
(△Tm/raod. ) (△Tm/mod. )
5' -GCGTTTTTTGCT-3' (天然） 47°C 45°C
5' -GCGXTTTTTGCT-3* (XT5) 50°C (+3°C) 49°C (+4°C)
5' -GCGTTXTTTGCT-3' (T2XT3) 49°C (+2°C) 49°C (+4°C)
5' - GCGTTTXTTGCT- 3' (T3XT2) 49°C (+2°C) 50°C (+5°C)
5' -GCGTTTTTXGCT-3* (T5X) 52°C (+4°C) 51°C (+6°C)
5' -GCGXXTTTTGCT-3* (X2T4) 51。C (+2°C) 53°C (+4°C)
5' -GCGTTXXTTGCT-3' (T2X2T2) 49°C (+1°C) 53°C (+4。C) 5' -GCGTTTTXXGCT-3' (T4X2) 54°C (+3.5°C) 55°C (+5°C)
5' -GCGXXXXXXGCT-3* (X6) 58°C (+1.8°C) 71°C (+4.3°C) a): 3' -CGCAAAAAACGA-5' . b): 3' -r(CGCAAAAAACGA).
表から明らかなように、 天然 DNA鎖中に本発明のヌクレオシド類縁体 （一般式 ( l a) ) のュニッ 卜 （X) が 1個あるいは 2個導入したオリゴマーでは、 相補 DNAオリゴマーとのハイプリ ド形成能が、 Tm値で評価して天然鎖よりも 2— 7度 (1修飾残基当たり 2度程度） 上昇し、 Tをすベて Xで置換した （X6) におい ては 1 1度も上昇した。 一方、 相補 RMに対するハイプリッ ド形成能を評価した ところ、 1個あるいは 2個導入したオリゴマ一では天然鎖よりも 4一 10度 （1 修飾残基当たり 4度から 6度） の Tm値の上昇が認められ、 しかも （X6) にお いては相補 RNAに対するハイブリツ ド形成能が更に強まり、 Tm値が 25度以上 (1修飾残基当たり 4度） も上昇が認められた。 このように、 天然鎖よりも Tm 値がかくも上昇する類縁体の例がなく、 また DNAよりも RNAに対する親和性が高 いことは、 本発明のビシクロオリゴヌクレオシド類縁体を構成単位としたオリゴ ヌクレオチド類縁体がァンチセンス分子として極めて高い性能と医薬品素材とし ての有用性を有していることを意味していると言える。
[実験例 2] ヌクレアーゼ酵素耐性の測定
15分間 3了。 Cに保ったオリゴヌクレオチドのバッファ一溶液（10〃M, 400 H) に蛇毒ホスホジエステラーゼのバッファー溶液 （0.003U/ml, 400 1)を混合した。 混合溶液を 37°Cに保った石英セル（800 il)に入れ、 オリゴヌクレオチドの分解 による紫外部吸収（260nm)の増加を SHIMADZU UV- 2100PCを用いて経時的に測定し た。 用いたバッファーの組成は Tris- HCl(pH8.6)0. lM、NaCl 0. lM、MgCl214mMであ り測定前に十分に脱気した。
半減期（t1/2)の測定
測定開始時（t=0)及び紫外部吸収が認められなくなった点の UV吸収の平均値 を示す時間を半減期 （t1/2)とした。
ォリゴヌクレオチド配列 t1/2 (秒） 5' -GTTTTTTTTTTTC-3' (天然型） 260
5' - GTTTTTTTTT- XX- C- 3' ( X 2 ) 850
また、 紫外部吸収の経時変化を示すチャートを図 1 (天然鎖） 及び図 2 ( X 2 ) に示した。 天然鎖は酸素反応開始後、 約 3 0分で紫外部吸収値が一定となり、 X 2では約 9 0分で一定となつた。
[産業上の利用可能性]
この類縁体の使用により、 生体内で酵素の加水分解を受けにく く、 センス鎖との 結合能が高く、 しかも合成が容易であるオリゴヌクレオチド類縁体アンチセンス 分子が提供される。
[配列表]
出願人の氏名 ：今西武
発明の名称：新規ビシクロヌクレオシド及びォリゴヌクレオチド類縁体 整理番号：
出願番号：
出願日 ：平成 10年 3月 曰
優先権番号：特願平 9一 53409号
優先日 ：平成 9年 3月 7曰
配列の数： 10 配列番号： 1
配列の長さ ： 12
配列の型： ヌクレオチド
鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' 一 GCGTTTTTTGCT - 3' 配列番号： 2
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体
鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' 一 GCGXTTTTTGCT - 3' 配列番号： 3
配列の長さ ： 12 配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' -GCGTTXTTTGCT-3' 配列番号： 4
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' -GCGTTTXTTGCT-3' 配列番号： 5
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' 一 GCGTTTTTXGCT - 3' 配列番号： 6
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列： W098/39352 PC雷 98/00945
5' 一 GCGXXTTTTGCT - 3' 配列番号： 7
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体
鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' - GCGTTXXTTGCT - 3' 配列番号： 8
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体
鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' 一 GCGTTTTXXGCT - 3' 配列番号： 9
配列の長さ ： 12
配列の型： ヌクレオチド、 ヌクレオチド類縁体
鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' -GCGXXXXXXGCT-3' 配列番号： 10
配列の長さ ： 13 配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' -GTTTTTTTTTTTC-3' 配列番号： 11
配列の長さ ： 13
配列の型： ヌクレオチド、 ヌクレオチド類縁体 鎖の数： 1本鎖
トポロジー：直鎖状
配列：
5' -GTTTTTTTTXXTC-3'

Claims

請求の範囲 一般式 （ I )
Figure imgf000045_0001
[式中、 Bはピリ ミジンもしくはプリン核酸塩基又はそれらの類縁体であり、 X及び Yは同一もしくは異なり、 水素、 アルキル基、 アルケニル基、 アルキニル 基、 シクロアルキル基、 ァラルキル基、 ァリール基、 ァシル基、 又はシリル基] で表わされるヌクレオシド類縁体もしくはそのァミダイ ト誘導体。
2. X、 Yがともに水素である請求項 1記載のヌクレオシド類縁体。
3. が 4, 4' -ジメ トキシトリチル （DMT r ) で、 Yが 2—シァノエトキシ (ジイソプロピルアミノ） ホスフイノ基 （アミダイ ト基） である請求項 1記載の モノヌクレオシドアミダイ ト誘導体。
4. 一般式 （ I a )
Figure imgf000045_0002
( Ι ) [式中、 Bはピリ ミジンもしくはプリン核酸塩基又はそれらの類縁体である] で 表される構造を 1または 2以上有するオリゴヌクレオチドまたはポリヌクレオチ ド類縁体。
5. —般式 （II)
Figure imgf000046_0001
( II )
[式中、 B '、 Bは同一または異なり、 ピリ ミジンもしくはプリン核酸塩基又は それらの類縁体であり、 Rは水素、 水酸基、 ハロゲン、 またはアルコキシ基であ り、 、 W2は同一または異なり、 水素、 アルキル基、 アルケニル基、 アルキニ ル基、 シクロアルキル基、 ァラルキル基、 ァリール基、 ァシル基、 シリル基また はリン酸残基もしくはリン酸ジエステル結合を介した天然型ヌクレオシド、 及び その類縁体またはこれらヌクレオシドを含むオリゴヌクレオチドもしくはポリヌ クレオチドであり、 n 1または n 2は同一または異なり、 0から 5 0の整数である (ただし、 n lまたは n 2が同時にゼロになることはない。 また n 2のすべてがゼ 口になることはない。 ） 、 n 3は 1〜5 0の整数である、 ただし、 n 1および Zま たは n 2が 2以上の場合には B 1と Bは同一でなくてもよく、 Rも同一でなくても よい] で表されるオリゴヌクレオチドもしくはポリヌクレオチド類縁体。
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CA002283509A CA2283509C (en) 1997-03-07 1998-03-09 Novel bicyclonucleoside and oligonucleotide analogue
DK98905804.5T DK1013661T4 (en) 1997-03-07 1998-03-09 2'-O, 4'-C-methylene bicyclonucleosides
DE98905804T DE98905804T1 (de) 1997-03-07 1998-03-09 Bicyclonukleosid- und oligonukleotid-analoga
AT98905804T ATE541576T2 (de) 1997-03-07 1998-03-09 2'-o,4'-c-methylen bicyclonukleoside
US13/533,781 USRE44779E1 (en) 1997-03-07 1998-03-09 Bicyclonucleoside and oligonucleotide analogues
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Cited By (563)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000047599A1 (fr) * 1999-02-12 2000-08-17 Sankyo Company, Limited Nouveaux analogues de nucleosides et d'oligonucleotides
WO2000056748A1 (en) * 1999-03-18 2000-09-28 Exiqon A/S Xylo-lna analogues
WO2000066604A2 (en) * 1999-05-04 2000-11-09 Exiqon A/S L-ribo-lna analogues
WO2001007455A1 (fr) * 1999-07-22 2001-02-01 Sankyo Company, Limited Analogues de bicyclonucléosides
WO2001048190A2 (en) * 1999-12-23 2001-07-05 Exiqon A/S Therapeutic uses of lna-modified oligonucleotides
US6303315B1 (en) 1999-03-18 2001-10-16 Exiqon A/S One step sample preparation and detection of nucleic acids in complex biological samples
US6316198B1 (en) 1999-03-18 2001-11-13 Exiqon A/S Detection of mutations in genes by specific LNA primers
WO2002018388A1 (fr) * 2000-08-29 2002-03-07 Takeshi Imanishi Analogues de nucleosides et derives d'oligonucleotides renfermant ces analogues
WO2003033696A1 (fr) * 2001-10-18 2003-04-24 Sankyo Company, Limited Compose antisens vegf
US6639059B1 (en) 1999-03-24 2003-10-28 Exiqon A/S Synthesis of [2.2.1]bicyclo nucleosides
US6670461B1 (en) 1997-09-12 2003-12-30 Exiqon A/S Oligonucleotide analogues
US6734291B2 (en) 1999-03-24 2004-05-11 Exiqon A/S Synthesis of [2.2.1]bicyclo nucleosides
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004072284A1 (en) 2003-02-11 2004-08-26 Antisense Therapeutics Ltd Modulation of insulin like growth factor i receptor expression
WO2004078922A2 (en) 2003-02-28 2004-09-16 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
WO2004096124A2 (en) 2003-04-01 2004-11-11 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US6822088B2 (en) 2001-07-17 2004-11-23 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides on solid support
WO2005019418A2 (en) 2003-08-18 2005-03-03 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 2 expression
WO2005049630A2 (en) 2003-11-17 2005-06-02 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
US7005265B1 (en) 2002-06-20 2006-02-28 Wenhong Fan Nonenzymatic catalytic signal amplification for nucleic acid hybridization assays
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
WO2007027894A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Antisense compounds having enhanced anti-microrna activity
US7229767B2 (en) 2001-03-27 2007-06-12 University Of Delaware Genomics applications for modified OLIGO nucleotides
WO2007106690A2 (en) 2006-03-15 2007-09-20 Siemens Healthcare Diagnostics Inc. Degenerate nucleobase analogs
US7358068B2 (en) 2002-09-13 2008-04-15 Replicor, Inc. Antiviral oligonucleotides
EP1959012A2 (en) 2004-12-29 2008-08-20 Exiqon A/S Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAs and their target mRNAs
EP1992643A2 (en) 2001-06-20 2008-11-19 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2011886A2 (en) 2002-04-16 2009-01-07 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7504495B2 (en) 2003-11-20 2009-03-17 Exiqon A/S Quencher compositions comprising anthraquinone moieties
WO2009044392A2 (en) 2007-10-03 2009-04-09 Quark Pharmaceuticals, Inc. Novel sirna structures
WO2009045469A2 (en) 2007-10-02 2009-04-09 Amgen Inc. Increasing erythropoietin using nucleic acids hybridizable to micro-rna and precursors thereof
EP2050763A2 (en) 2005-03-10 2009-04-22 Genentech, Inc. Methods and compositions for modulating vascular integrity
EP2067472A1 (en) 2002-01-02 2009-06-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7566535B2 (en) 2002-03-07 2009-07-28 University Of Delaware Enhanced oligonucleotide-mediated nucleic acid sequence alteration
WO2009093384A1 (ja) * 2008-01-24 2009-07-30 National Institute Of Advanced Industrial Science And Technology ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
EP2090665A2 (en) 2006-10-20 2009-08-19 Exiqon A/S Novel human microRNAs associated with cancer
WO2009149182A1 (en) 2008-06-04 2009-12-10 The Board Of Regents Of The University Of Texas System Modulation of gene expression through endogenous small rna targeting of gene promoters
WO2009147684A2 (en) 2008-06-06 2009-12-10 Quark Pharmaceuticals, Inc. Compositions and methods for treatment of ear disorders
EP2143437A1 (en) 2001-09-18 2010-01-13 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2010014592A1 (en) 2008-07-29 2010-02-04 The Board Of Regents Of The University Of Texas Sytem Selective inhibition of polyglutamine protein expression
WO2010024231A1 (ja) * 2008-08-26 2010-03-04 株式会社日立ハイテクノロジーズ 高発現遺伝子由来のcDNAクローンの含有率を低減させたcDNAライブラリーの作製方法
EP2161283A1 (en) 2003-11-17 2010-03-10 Genentech, Inc. Compositions comprising antibodies against CD79b conjugated to a growth inhibitory agent or cytotoxic agent and methods for the treatment of tumor of hematopoietic origin
WO2010027831A1 (en) 2008-08-25 2010-03-11 Excaliard Pharmaceuticals, Inc. Method for reducing scarring during wound healing using antisense compounds directed to ctgf
US7687617B2 (en) 2002-11-18 2010-03-30 Santaris Pharma A/S Oligonucleotides with alternating segments of locked and non-locked nucleotides
US7695902B2 (en) 1996-06-06 2010-04-13 Isis Pharmaceuticals, Inc. Oligoribonucleotides and ribonucleases for cleaving RNA
EP2174945A1 (en) 2001-08-01 2010-04-14 Genzyme Corporation Antisense modulation of apolipoprotein B expression
WO2010042281A2 (en) 2008-08-25 2010-04-15 Excaliard Pharmaceuticals Antisense oligonucleotides directed against connective tissue growth factor and uses thereof
EP2179996A1 (en) 2000-11-28 2010-04-28 Applera Corporation Sulfonated diarylrhodamine dyes
EP2196544A1 (en) 2001-11-21 2010-06-16 Applied Biosystems, LLC Kit for ligation detection assays using codeable labels
US7745122B2 (en) 2005-07-15 2010-06-29 Applied Biosystems, Llc Analyzing messenger RNA and micro RNA in the same reaction mixture
WO2010074562A1 (en) 2008-12-22 2010-07-01 Keygene N.V. Use of double stranded rna to increase the efficiency of targeted gene alteration in plant protoplasts
WO2010080452A2 (en) 2008-12-18 2010-07-15 Quark Pharmaceuticals, Inc. siRNA COMPOUNDS AND METHODS OF USE THEREOF
EP2208796A2 (en) 2005-01-06 2010-07-21 Applied Biosystems, LLC Polypeptides having nucleic acid binding activity and compositions and methods for nucleic acid amplification
WO2010091308A2 (en) 2009-02-06 2010-08-12 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP2218727A1 (en) 2003-06-02 2010-08-18 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
EP2221376A2 (en) 2001-06-21 2010-08-25 Isis Pharmaceuticals, Inc. Antisense modulation of superoxide dismutase 1, soluble expression
US7807372B2 (en) 2007-06-04 2010-10-05 Northwestern University Screening sequence selectivity of oligonucleotide-binding molecules using nanoparticle based colorimetric assay
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
EP2241572A2 (en) 2003-06-03 2010-10-20 Eli Lilly And Company Modulation of survivin expression
WO2010120420A1 (en) 2009-04-15 2010-10-21 Northwestern University Delivery of oligonucleotide-functionalized nanoparticles
WO2010124231A2 (en) 2009-04-24 2010-10-28 The Board Of Regents Of The University Of Texas System Modulation of gene expression using oligomers that target gene regions downstream of 3' untranslated regions
US7829275B2 (en) 2001-07-20 2010-11-09 North Carolina State University Light addressable electrochemical detection of duplex structures
WO2010135384A2 (en) 2009-05-21 2010-11-25 Siemens Healthcare Diagnostics Inc. Universal tags with non-natural nucleobases
EP2256200A2 (en) 2003-09-18 2010-12-01 ISIS Pharmaceuticals, Inc. Modulation of eIF4E expression
EP2256213A1 (en) 2000-06-06 2010-12-01 Applied Biosystems, LLC Asynchronous primed PCR
EP2270230A2 (en) 2001-10-09 2011-01-05 ISIS Pharmaceuticals, Inc. Antisense modulation of insulin-like growth factor binding protein 5 expression
EP2270231A2 (en) 2001-10-09 2011-01-05 ISIS Pharmaceuticals, Inc. Antisense modulation of insulin-like growth factor binding protein 5 expression
EP2272958A1 (en) 2002-09-26 2011-01-12 ISIS Pharmaceuticals, Inc. Modulation of forkhead box O1A expression
EP2272985A1 (en) 2001-08-07 2011-01-12 ISIS Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (A) expression
EP2272857A1 (en) 2003-04-28 2011-01-12 ISIS Pharmaceuticals, Inc. Modulation of glucagon receptor expression
EP2280019A1 (en) 2001-07-25 2011-02-02 ISIS Pharmaceuticals, Inc. Antisense modulation of C-reactive protein expression
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
EP2281869A2 (en) 2003-03-21 2011-02-09 ISIS Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 1 expression
WO2011028950A1 (en) 2009-09-02 2011-03-10 Genentech, Inc. Mutant smoothened and methods of using the same
WO2011047307A1 (en) 2009-10-15 2011-04-21 Ibis Biosciences, Inc. Multiple displacement amplification
WO2011050194A1 (en) 2009-10-22 2011-04-28 Genentech, Inc. Methods and compositions for modulating hepsin activation of macrophage-stimulating protein
WO2011053994A1 (en) 2009-11-02 2011-05-05 Alnylam Pharmaceuticals, Inc. Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter
WO2011052436A1 (ja) 2009-10-29 2011-05-05 国立大学法人大阪大学 架橋型人工ヌクレオシドおよびヌクレオチド
WO2011056687A2 (en) 2009-10-27 2011-05-12 Swift Biosciences, Inc. Polynucleotide primers and probes
WO2011056215A1 (en) 2009-11-03 2011-05-12 Landers James P Versatile, visible method for detecting polymeric analytes
WO2011063403A1 (en) 2009-11-23 2011-05-26 Swift Biosciences, Inc. Devices to extend single stranded target molecules
WO2011066503A2 (en) 2009-11-30 2011-06-03 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2333115A1 (en) 2005-12-22 2011-06-15 Keygene N.V. Alternative nucleotides for improved targeted nucleotide exchange
EP2332955A2 (en) 2001-07-30 2011-06-15 ISIS Pharmaceuticals, Inc. Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression
WO2011072091A1 (en) 2009-12-09 2011-06-16 Quark Pharmaceuticals, Inc. Methods and compositions for treating diseases, disorders or injury of the cns
EP2336319A1 (en) 2002-11-13 2011-06-22 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2336318A1 (en) 2002-11-13 2011-06-22 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2338991A2 (en) 2005-08-29 2011-06-29 Regulus Therapeutics, Inc Methods for use in modulating MIR-122a
WO2011085271A2 (en) 2010-01-08 2011-07-14 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2011085056A1 (en) 2010-01-07 2011-07-14 Quark Pharmaceuticals, Inc. Oligonucleotide compounds comprising non-nucleotide overhangs
WO2011097388A1 (en) 2010-02-03 2011-08-11 Alnylam Pharmaceuticals, Inc. Selective inhibition of polyglutamine protein expression
EP2360277A1 (en) 2006-05-03 2011-08-24 Geisinger Clinic Methods for diagnosing and predicting non-alcoholic steatohepatitis (NASH)
WO2011105902A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-beta (c8-beta) and uses thereof
WO2011105900A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-alpha (c8-alpha) and uses thereof
WO2011106297A2 (en) 2010-02-23 2011-09-01 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2011105901A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 9 (c9) and uses thereof
EP2363480A2 (en) 2004-01-20 2011-09-07 Isis Pharmaceuticals, Inc. Modulation of glucocorticoid receptor expression
EP2363482A1 (en) 2006-05-05 2011-09-07 Isis Pharmaceuticals, Inc. Compounds and methods for modulating gene expression
EP2363503A1 (en) 2002-11-23 2011-09-07 ISIS Pharmaceuticals, Inc. Modulation of HIF1A and HIF2A expression
WO2011108930A1 (en) 2010-03-04 2011-09-09 Interna Technologies Bv A MiRNA MOLECULE DEFINED BY ITS SOURCE AND ITS DIAGNOSTIC AND THERAPEUTIC USES IN DISEASES OR CONDITIONS ASSOCIATED WITH EMT
US8017338B2 (en) 2007-11-20 2011-09-13 Life Technologies Corporation Reversible di-nucleotide terminator sequencing
WO2011113054A2 (en) 2010-03-12 2011-09-15 Aurasense Llc Crosslinked polynucleotide structure
WO2011133695A2 (en) 2010-04-20 2011-10-27 Swift Biosciences, Inc. Materials and methods for nucleic acid fractionation by solid phase entrapment and enzyme-mediated detachment
US8048998B2 (en) 2007-01-19 2011-11-01 Exiqon A/S Mediated cellular delivery of LNA oligonucleotides
WO2011134474A1 (en) 2010-04-30 2011-11-03 Exiqon A/S In situ hybridization method and buffer
WO2011139917A1 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression
WO2011139702A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. Modified nucleosides and oligomeric compounds prepared therefrom
WO2011139985A1 (en) 2010-05-03 2011-11-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2011139695A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom
WO2011139699A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
WO2011139911A2 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Lipid formulated single stranded rna
EP2388327A1 (en) 2006-01-27 2011-11-23 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
EP2388318A1 (en) 2001-12-10 2011-11-23 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
WO2011150226A1 (en) 2010-05-26 2011-12-01 Landers James P Method for detecting nucleic acids based on aggregate formation
WO2011156278A1 (en) 2010-06-07 2011-12-15 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2011156202A1 (en) 2010-06-08 2011-12-15 Isis Pharmaceuticals, Inc. Substituted 2 '-amino and 2 '-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
US8084437B2 (en) 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
EP2405024A1 (en) 2005-07-15 2012-01-11 Life Technologies Corporation Hot start reverse transcription by primer design
WO2012005572A1 (en) 2010-07-06 2012-01-12 Interna Technologies Bv Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma, or in diseases or conditions associated with activated braf pathway
EP2410053A1 (en) 2006-10-18 2012-01-25 Isis Pharmaceuticals, Inc. Antisense compounds
EP2412724A1 (en) 2010-07-29 2012-02-01 Centre National de la Recherche Scientifique (C.N.R.S) Regulation of Glypican 4 activity to modulate the fate of stem cells and uses thereof
WO2012047968A2 (en) 2010-10-05 2012-04-12 Genentech, Inc. Mutant smoothened and methods of using the same
EP2441449A1 (en) 2003-04-16 2012-04-18 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein C-III expression
EP2444482A1 (en) 2003-11-03 2012-04-25 Isis Pharmaceuticals, Inc. Modulation of SGLT2 expression
EP2447274A2 (en) 2008-10-24 2012-05-02 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2012061778A2 (en) 2010-11-05 2012-05-10 Genalyte, Inc. Optical analyte detection systems and methods of use
WO2012068405A2 (en) 2010-11-17 2012-05-24 Isis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
US8188255B2 (en) 2006-10-20 2012-05-29 Exiqon A/S Human microRNAs associated with cancer
EP2458011A1 (en) 2005-10-03 2012-05-30 Life Technologies Corporation Compositions, methods, and kits for amplifying nucleic acids
US8192937B2 (en) 2004-04-07 2012-06-05 Exiqon A/S Methods for quantification of microRNAs and small interfering RNAs
WO2012074385A1 (en) 2010-12-02 2012-06-07 Keygene N.V. Targeted alteration of dna
WO2012074386A1 (en) 2010-12-02 2012-06-07 Keygene N.V. Targeted alteration of dna with oligonucleotides
EP2468865A1 (en) 2004-02-06 2012-06-27 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of stat3 expression
EP2474617A1 (en) 2011-01-11 2012-07-11 InteRNA Technologies BV Mir for treating neo-angiogenesis
WO2012096523A2 (en) 2011-01-11 2012-07-19 Seegene, Inc. Detection of target nucleic acid sequences by pto cleavage and extension assay
EP2484781A2 (en) 2006-08-01 2012-08-08 Applied Biosystems, LLC Detection of analytes and nucleic acids
WO2012106508A1 (en) 2011-02-02 2012-08-09 Pfizer Inc. Method of treating keloids or hypertrophic scars using antisense compounds targeting connective tissue growth factor (ctgf)
WO2012106509A1 (en) 2011-02-02 2012-08-09 The Trustees Of Princeton University Sirtuin modulators as virus production modulators
WO2012109495A1 (en) 2011-02-09 2012-08-16 Metabolic Solutions Development Company, Llc Cellular targets of thiazolidinediones
WO2012118911A1 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Oligonucleotide modulators of the toll-like receptor pathway
WO2012118910A2 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Compositions and methods for treating lung disease and injury
EP2505648A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PTP1B
WO2012134195A2 (en) 2011-03-29 2012-10-04 Seegene, Inc. Detection of target nucleic acid sequence by pto cleavage and extension-dependent cleavage
EP2508607A1 (en) 2011-04-07 2012-10-10 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
US8293684B2 (en) 2006-11-29 2012-10-23 Exiqon Locked nucleic acid reagents for labelling nucleic acids
WO2012149154A1 (en) 2011-04-26 2012-11-01 Swift Biosciences, Inc. Polynucleotide primers and probes
WO2012149495A1 (en) 2011-04-27 2012-11-01 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein ciii (apociii) expression
WO2012149339A2 (en) 2011-04-29 2012-11-01 Sequenom, Inc. Quantification of a minority nucleic acid species
WO2012150835A2 (en) 2011-05-04 2012-11-08 Seegene, Inc. Detection of target nucleic acid sequences by po cleavage and hybridization
WO2012151289A2 (en) 2011-05-02 2012-11-08 University Of Virginia Patent Foundation Method and system to detect aggregate formation on a substrate
WO2012151268A1 (en) 2011-05-02 2012-11-08 University Of Virginia Patent Foundation Method and system for high throughput optical and label free detection of analytes
EP2530157A2 (en) 2003-07-31 2012-12-05 Regulus Therapeutics, Inc Oligomeric compounds and compositions for use in modulation of small non-coding rnas
WO2012170957A2 (en) 2011-06-08 2012-12-13 Nitto Denko Corporation Retinoid-liposomes for enhancing modulation of hsp47 expression
WO2012170347A1 (en) 2011-06-09 2012-12-13 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2012174476A2 (en) 2011-06-16 2012-12-20 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
WO2013003808A1 (en) 2011-06-29 2013-01-03 Isis Pharmaceuticals, Inc. Methods for modulating kallikrein (klkb1) expression
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
WO2013040499A1 (en) 2011-09-14 2013-03-21 Northwestern University Nanoconjugates able to cross the blood-brain barrier
WO2013043817A1 (en) 2011-09-20 2013-03-28 Isis Phamaceuticals, Inc. Antisense modulation of gcgr expression
WO2013063313A1 (en) 2011-10-25 2013-05-02 Isis Pharmaceuticals, Inc. Antisense modulation of gccr expression
WO2013067076A2 (en) 2011-11-03 2013-05-10 Quark Pharmaceuticals, Inc. Methods and compositions for neuroprotection
WO2013070786A1 (en) 2011-11-07 2013-05-16 Isis Pharmaceuticals, Inc. Modulation of tmprss6 expression
WO2013090457A2 (en) 2011-12-12 2013-06-20 Oncoimmunin Inc. In vivo delivery of oligonucleotides
WO2013096837A1 (en) 2011-12-22 2013-06-27 Isis Pharmaceuticals, Inc. Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1(malat-1) expression
WO2013095132A1 (en) 2011-12-22 2013-06-27 Interna Technologies B.V. Mirna for treating head and neck cancer
WO2013120003A1 (en) 2012-02-08 2013-08-15 Isis Pharmaceuticals, Inc. Modulation of rna by repeat targeting
WO2013133561A1 (en) 2012-03-05 2013-09-12 Seegene, Inc. Detection of nucleotide variation on target nucleic acid sequence by pto cleavage and extension assay
WO2013138536A1 (en) 2012-03-13 2013-09-19 Swift Biosciences, Inc. Methods and compositions for size-controlled homopolymer tailing of substrate polynucleotides by a nucleic acid polymerase
WO2013138251A1 (en) 2012-03-12 2013-09-19 The Board Of Trustes Of The University Of Illinois Optical analyte detection systems with magnetic enhancement and methods of use
WO2013154799A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleosides and oligomeric compounds prepared therefrom
WO2013154798A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
WO2013177248A2 (en) 2012-05-22 2013-11-28 Isis Pharmaceuticals, Inc. Modulation of enhancer rna mediated gene expression
WO2013177468A2 (en) 2012-05-24 2013-11-28 Isis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein(a) expression
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
WO2014004572A2 (en) 2012-06-25 2014-01-03 Isis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
WO2014018930A1 (en) 2012-07-27 2014-01-30 Isis Pharmaceuticals. Inc. Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen
EP2700720A2 (en) 2004-03-15 2014-02-26 Isis Pharmaceuticals, Inc. Compositions and methods for optimizing cleavage of RNA by RNASE H
WO2014039916A1 (en) 2012-09-06 2014-03-13 The University Of Chicago Antisense polynucleotides to induce exon skipping and methods of treating dystrophies
US8680254B2 (en) 2009-01-14 2014-03-25 Philadelphia Health & Education Corporation Modulation of pre-mRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
WO2014045126A2 (en) 2012-09-18 2014-03-27 Uti Limited Partnership Treatment of pain by inhibition of usp5 de-ubiquitinase
WO2014046212A1 (ja) 2012-09-21 2014-03-27 国立大学法人大阪大学 グアニジン架橋を有する人工ヌクレオシドおよびオリゴヌクレオチド
WO2014059238A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals Inc Modulation of androgen receptor expression
WO2014062686A1 (en) 2012-10-15 2014-04-24 Isis Pharmaceuticals, Inc. Methods for modulating c9orf72 expression
US8710209B2 (en) 2009-12-09 2014-04-29 Nitto Denko Corporation Modulation of HSP47 expression
WO2014070868A1 (en) 2012-10-31 2014-05-08 Isis Pharmaceuticals Inc Cancer treatment
WO2014072357A1 (en) 2012-11-06 2014-05-15 Interna Technologies B.V. Combination for use in treating diseases or conditions associated with melanoma, or treating diseases or conditions associated with activated b-raf pathway
WO2014076195A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Oligonucleotide conjugates
WO2014080004A1 (en) 2012-11-26 2014-05-30 Santaris Pharma A/S Compositions and methods for modulation of fgfr3 expression
WO2014113540A1 (en) 2013-01-16 2014-07-24 Iowa State University Research Foundation, Inc. A deep intronic target for splicing correction on spinal muscular atrophy gene
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
WO2014118267A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Lna oligonucleotide carbohydrate conjugates
WO2014126229A1 (ja) 2013-02-18 2014-08-21 塩野義製薬株式会社 含窒素複素環構造を有するヌクレオシド及びヌクレオチド
EP2770065A1 (en) 2013-02-25 2014-08-27 Seegene, Inc. Detection of nucleotide variation on target nucleic acid sequence
WO2014134179A1 (en) 2013-02-28 2014-09-04 The Board Of Regents Of The University Of Texas System Methods for classifying a cancer as susceptible to tmepai-directed therapies and treating such cancers
WO2014134144A1 (en) 2013-02-28 2014-09-04 The General Hospital Corporation Mirna profiling compositions and methods of use
WO2014142575A1 (en) 2013-03-13 2014-09-18 Seegene, Inc. Quantification of target nucleic acid using melting peak analysis
WO2014152673A1 (en) 2013-03-14 2014-09-25 Shire Human Genetic Therapies, Inc. Quantitative assessment for cap efficiency of messenger rna
WO2014152659A1 (en) 2013-03-14 2014-09-25 Shire Human Genetic Therapies, Inc. Quantitative assessment for cap efficiency of messenger rna
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
WO2014176259A1 (en) 2013-04-22 2014-10-30 Icahn School Of Medicine At Mount Sinai Mutations in pdgfrb and notch3 as causes of autosomal dominant infantile myofibromatosis
WO2014179335A1 (en) 2013-04-29 2014-11-06 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
US8889350B2 (en) 2010-03-26 2014-11-18 Swift Biosciences, Inc. Methods and compositions for isolating polynucleotides
WO2014197938A1 (en) 2013-06-13 2014-12-18 Antisense Therapeutics Ltd Combination therapy
WO2014205449A2 (en) 2013-06-21 2014-12-24 Isis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
WO2015002971A2 (en) 2013-07-02 2015-01-08 Isis Pharmaceuticals, Inc. Modulators of growth hormone receptor
EP2826863A1 (en) 2007-05-30 2015-01-21 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
WO2015010135A2 (en) 2013-07-19 2015-01-22 Isis Pharmaceuticals, Inc. Compositions for modulating tau expression
WO2015008985A1 (en) 2013-07-15 2015-01-22 Seegene, Inc. Detection of target nucleic acid sequence by pto cleavage and extension-dependent immobilized oligonucleotide hybridization
WO2015021457A2 (en) 2013-08-09 2015-02-12 Isis Pharmaceuticals, Inc. Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
WO2015031679A2 (en) 2013-08-28 2015-03-05 Isis Pharmaceuticals, Inc. Modulation of prekallikrein (pkk) expression
US8999947B2 (en) 2005-06-14 2015-04-07 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
US8999634B2 (en) 2007-04-27 2015-04-07 Quest Diagnostics Investments Incorporated Nucleic acid detection combining amplification with fragmentation
WO2015057008A2 (en) 2013-10-18 2015-04-23 Seegene, Inc. Detection of target nucleic acid sequence on solid phase by pto cleavage and extension using hcto assay
WO2015057998A1 (en) 2013-10-16 2015-04-23 The University Of British Columbia Device for formulating particles at small volumes
US9029335B2 (en) 2012-10-16 2015-05-12 Isis Pharmaceuticals, Inc. Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2015100394A1 (en) 2013-12-24 2015-07-02 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US9096895B2 (en) 2009-02-02 2015-08-04 Exiqon A/S Method for quantification of small RNA species
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
WO2015120075A2 (en) 2014-02-04 2015-08-13 Genentech, Inc. Mutant smoothened and methods of using the same
WO2015125783A1 (ja) * 2014-02-18 2015-08-27 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
EP2913402A1 (en) 2010-07-16 2015-09-02 Tocagen Inc. Retrovirus detection
US9139827B2 (en) 2008-11-24 2015-09-22 Northwestern University Polyvalent RNA-nanoparticle compositions
WO2015143246A1 (en) 2014-03-19 2015-09-24 Isis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
WO2015153800A2 (en) 2014-04-01 2015-10-08 Isis Pharmaceuticals, Inc. Compositions for modulating sod-1 expression
WO2015164693A1 (en) 2014-04-24 2015-10-29 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising alpha-beta-constrained nucleic acid
US9205102B2 (en) 2013-12-06 2015-12-08 The University Of British Columbia Method for treatment of castration-resistant prostate cancer
WO2015190922A1 (en) 2014-06-10 2015-12-17 Erasmus University Medical Center Rotterdam Antisense oligonucleotides useful in treatment of pompe disease
WO2016006697A1 (ja) * 2014-07-10 2016-01-14 賢二 中野 アンチセンス抗悪性腫瘍剤
DE202013012241U1 (de) 2012-05-25 2016-01-18 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
WO2016017422A1 (ja) * 2014-07-31 2016-02-04 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
EP2982753A1 (en) 2008-04-18 2016-02-10 Baxter International Inc Microsphere-based composition for preventing and/or reversing new-onset autoimmune diabetes
WO2016027263A2 (en) 2014-08-21 2016-02-25 Omrix Biopharmaceuticals Ltd. Stabilized thrombin
WO2016027168A2 (en) 2014-08-20 2016-02-25 Lifesplice Pharma Llc Splice modulating oligonucleotides and methods of use thereof
WO2016028940A1 (en) 2014-08-19 2016-02-25 Northwestern University Protein/oligonucleotide core-shell nanoparticle therapeutics
WO2016033424A1 (en) 2014-08-29 2016-03-03 Genzyme Corporation Methods for the prevention and treatment of major adverse cardiovascular events using compounds that modulate apolipoprotein b
WO2016034611A1 (en) 2014-09-02 2016-03-10 Max-Delbrück-Centrum für Molekulare Medizin Antisense oligonucleotides targeting 3'utr region of a20
US9290816B2 (en) 2010-06-07 2016-03-22 Firefly Bioworks Inc. Nucleic acid detection and quantification by post-hybridization labeling and universal encoding
WO2016054032A1 (en) 2014-09-29 2016-04-07 The Jackson Laboratory High efficiency, high throughput generation of genetically modified mammals by electroporation
US9310361B2 (en) 2006-10-05 2016-04-12 Massachusetts Institute Of Technology Multifunctional encoded particles for high-throughput analysis
US9315811B2 (en) 2011-06-10 2016-04-19 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
US9340784B2 (en) 2012-03-19 2016-05-17 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
WO2016075584A1 (en) 2014-11-10 2016-05-19 Glaxosmithkline Intellectual Property (No.2) Limited Combination long acting compositions and methods for hepatitis c
WO2016075583A1 (en) 2014-11-10 2016-05-19 Glaxosmithkline Intelle Ctual Property (No.2) Limited Long acting pharmaceutical compositions for hepatitis c
WO2016081911A2 (en) 2014-11-21 2016-05-26 Northwestern University The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates
EP3031920A1 (en) 2010-07-19 2016-06-15 Ionis Pharmaceuticals, Inc. Modulation of dystrophia myotonica-protein kinase (dmpk) expression
WO2016100716A1 (en) 2014-12-18 2016-06-23 Vasant Jadhav Reversirtm compounds
US9376690B2 (en) 2009-10-30 2016-06-28 Northwestern University Templated nanoconjugates
US9382540B2 (en) 2014-05-01 2016-07-05 Isis Pharmaceuticals, Inc Compositions and methods for modulating angiopoietin-like 3 expression
US9403865B2 (en) 2012-08-15 2016-08-02 Ionis Pharmaceuticals, Inc. Method of preparing oligomeric compounds using modified capping protocols
WO2016126972A1 (en) 2015-02-04 2016-08-11 Genentech, Inc. Mutant smoothened and methods of using the same
US9416360B2 (en) 2010-11-05 2016-08-16 MiRagen Therapeutics, Inc. Base modified oligonucleotides
WO2016138353A1 (en) 2015-02-26 2016-09-01 Ionis Pharmaceuticals, Inc. Allele specific modulators of p23h rhodopsin
WO2016141236A1 (en) 2015-03-03 2016-09-09 Ionis Pharmaceuticals, Inc. Compositions for modulating mecp2 expression
US9464106B2 (en) 2002-10-21 2016-10-11 Exiqon A/S Oligonucleotides useful for detecting and analyzing nucleic acids of interest
WO2016164602A1 (en) 2015-04-08 2016-10-13 The University Of Chicago Compositions and methods for correcting limb girdle muscular dystrophy type 2c using exon skipping
WO2016168592A2 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
WO2016196655A1 (en) 2015-06-03 2016-12-08 The Regents Of The University Of California Cas9 variants and methods of use thereof
US9523094B2 (en) 2012-10-11 2016-12-20 Ionis Pharmaceuticals, Inc. Methods of treating kennedy's disease
WO2017015109A1 (en) 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
WO2017018360A1 (ja) * 2015-07-24 2017-02-02 日産化学工業株式会社 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド
WO2017023861A1 (en) 2015-08-03 2017-02-09 The Regents Of The University Of California Compositions and methods for modulating abhd2 activity
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US9580743B2 (en) 2005-09-09 2017-02-28 Life Technologies Corporation SSB-polymerase fusion proteins
WO2017032726A1 (en) 2015-08-24 2017-03-02 Roche Innovation Center Copenhagen A/S Lna-g process
US9593374B2 (en) 2005-08-17 2017-03-14 Lianidou Evriklia Composition and method for determination of CK19 expression
US9598724B2 (en) 2007-06-01 2017-03-21 Ibis Biosciences, Inc. Methods and compositions for multiple displacement amplification of nucleic acids
WO2017047816A1 (ja) * 2015-09-18 2017-03-23 田辺三菱製薬株式会社 架橋型核酸ＧｕＮＡ、その製造方法および中間体化合物
US9605313B2 (en) 2012-03-02 2017-03-28 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9610362B2 (en) 2012-03-16 2017-04-04 Valerion Therapeutics, Llc Antisense conjugates for decreasing expression of DMPK
WO2017064546A1 (en) 2015-09-24 2017-04-20 Crispr Therapeutics Ag Novel family of rna-programmable endonucleases and their uses in genome editing and other applications
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
WO2017075421A1 (en) 2015-10-29 2017-05-04 Temple University-Of The Commonwealth System Of Higher Education Modification of 3' terminal ends of nucleic acids by dna polymerase theta
US9644207B2 (en) 2013-03-14 2017-05-09 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Tau expression
WO2017079442A1 (en) 2015-11-04 2017-05-11 Icahn School Of Medicine At Mount Sinai Methods of treating tumors and cancer, and identifying candidate subjects for such treatment
US9650421B2 (en) 2011-09-02 2017-05-16 Northwestern University Self-assembled nanostructures
WO2017098468A1 (en) 2015-12-09 2017-06-15 Novartis Ag Label-free analysis of rna capping efficiency using rnase h, probes and liquid chromatography/mass spectrometry
WO2017099579A1 (en) 2015-12-07 2017-06-15 Erasmus University Medical Center Rotterdam Enzymatic replacement therapy and antisense therapy for pompe disease
US9688707B2 (en) 2014-12-30 2017-06-27 Ionis Pharmaceuticals, Inc. Bicyclic morpholino compounds and oligomeric compounds prepared therefrom
WO2017109679A1 (en) 2015-12-21 2017-06-29 Novartis Ag Compositions and methods for decreasing tau expression
US9695418B2 (en) 2012-10-11 2017-07-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
US9701708B2 (en) 2013-01-31 2017-07-11 Ionis Pharmaceuticals, Inc. Method of preparing oligomeric compounds using modified coupling protocols
WO2017124086A1 (en) 2016-01-15 2017-07-20 The Jackson Laboratory Genetically modified non-human mammals by multi-cycle electroporation of cas9 protein
WO2017136558A1 (en) 2016-02-04 2017-08-10 Curis, Inc. Mutant smoothened and methods of using the same
EP3208347A1 (en) 2010-02-08 2017-08-23 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2017147483A1 (en) 2016-02-26 2017-08-31 The Board Of Trustees Of The Leland Stanford Junior University Multiplexed single molecule rna visualization with a two-probe proximity ligation system
WO2017157899A1 (en) 2016-03-14 2017-09-21 F. Hoffmann-La Roche Ag Oligonucleotides for reduction of pd-l1 expression
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
US9796979B2 (en) 2011-03-03 2017-10-24 Quark Pharmaceuticals Inc. Oligonucleotide modulators of the toll-like receptor pathway
WO2017189730A1 (en) 2016-04-26 2017-11-02 Icahn School Of Medicine At Mount Sinai Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment
EP3248618A1 (en) 2009-04-22 2017-11-29 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long rna molecules
US9846126B2 (en) 2008-10-27 2017-12-19 Genalyte, Inc. Biosensors based on optical probing and sensing
WO2017218573A1 (en) 2016-06-16 2017-12-21 The Regents Of The University Of California Methods and compositions for detecting a target rna
WO2017216390A1 (en) 2016-06-17 2017-12-21 F. Hoffmann-La Roche Ag Nucleic acid molecules for reduction of papd5 or papd7 mrna for treating hepatitis b infection
WO2018002105A1 (en) 2016-07-01 2018-01-04 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
EP3276004A2 (en) 2009-06-08 2018-01-31 Quark Pharmaceuticals, Inc. Methods for treating chronic kidney disease
WO2018026282A1 (en) 2016-08-05 2018-02-08 Erasmus University Medical Center Rotterdam (Erasmus Mc) Antisense oligomeric compound for pompe disease
WO2018026284A1 (en) 2016-08-05 2018-02-08 Erasmus University Medical Center Rotterdam (Erasmus Mc) Natural cryptic exon removal by pairs of antisense oligonucleotides
US9890427B2 (en) 2007-02-09 2018-02-13 Northwestern University Particles for detecting intracellular targets
WO2018044239A1 (en) 2016-09-01 2018-03-08 Agency For Science, Technology And Research Method of treating cancer by antisense oligonucleotides targeting prdm15
US9914922B2 (en) 2012-04-20 2018-03-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
US9926593B2 (en) 2009-12-22 2018-03-27 Sequenom, Inc. Processes and kits for identifying aneuploidy
US9932581B2 (en) 2013-05-01 2018-04-03 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein C-III expression
EP3312189A1 (en) 2011-04-21 2018-04-25 Ionis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
WO2018080393A1 (en) 2016-10-28 2018-05-03 Agency For Science, Technology And Research Antisense oligonucleotides
EP3321361A1 (en) 2010-02-08 2018-05-16 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2018087200A1 (en) 2016-11-11 2018-05-17 Roche Innovation Center Copenhagen A/S Therapeutic oligonucleotides capture and detection
US9983206B2 (en) 2013-03-15 2018-05-29 The Board Of Trustees Of The University Of Illinois Methods and compositions for enhancing immunoassays
US9994855B2 (en) 2014-05-01 2018-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
US10017764B2 (en) 2011-02-08 2018-07-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2018130583A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
WO2018130585A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
WO2018130582A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018130584A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
US10036019B2 (en) 2014-03-17 2018-07-31 Ionis Pharmaceuticals, Inc. Bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom
EP3354750A1 (en) 2012-07-18 2018-08-01 Siemens Healthcare Diagnostics Inc. Kit of normalizing biological samples
WO2018143475A1 (ja) 2017-02-06 2018-08-09 日産化学工業株式会社 一本鎖オリゴヌクレオチド
EP3375877A1 (en) 2013-11-18 2018-09-19 Crispr Therapeutics AG Crispr-cas system materials and methods
WO2018181428A1 (ja) 2017-03-29 2018-10-04 塩野義製薬株式会社 核酸医薬及び多分岐脂質の複合体
US10098958B2 (en) 2009-01-08 2018-10-16 Northwestern University Delivery of oligonucleotide functionalized nanoparticles
EP3400947A1 (en) 2013-02-14 2018-11-14 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein c-iii (apociii) expression in lipoprotein lipase deficient (lpld) populations
WO2018220034A1 (en) 2017-06-01 2018-12-06 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
US10182988B2 (en) 2013-12-03 2019-01-22 Northwestern University Liposomal particles, methods of making same and uses thereof
WO2019022196A1 (ja) 2017-07-26 2019-01-31 日産化学株式会社 一本鎖オリゴヌクレオチド
US10196637B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Retinoid-lipid drug carrier
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
US10221414B2 (en) 2013-10-11 2019-03-05 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
WO2019045075A1 (ja) 2017-08-31 2019-03-07 田辺三菱製薬株式会社 Ｉｌ－３３アンタゴニストを含む子宮内膜症治療剤
WO2019066461A2 (en) 2017-09-29 2019-04-04 Seegene, Inc. DETECTION OF TARGET NUCLEIC ACID SEQUENCES BY CLEAVAGE ANALYSIS AND EXTENSION OF PTO
EP3466960A2 (en) 2011-04-01 2019-04-10 Ionis Pharmaceuticals, Inc. Modulation of signal transducer and activator of transcription 3 (stat3) expression
WO2019073018A1 (en) 2017-10-13 2019-04-18 Roche Innovation Center Copenhagen A/S METHODS OF IDENTIFYING ANTISENSE OLIGONUCLEOTIDE IMPROVED OLIGONUCLEOTIDE PHOSPHOROTHIOATE STEREODEFINIS VARIANTS USING PARTIALLY STEREODEFINIS OLIGONUCLEOTIDE SUB LIBRARIES
WO2019076842A1 (en) 2017-10-16 2019-04-25 F. Hoffmann-La Roche Ag NUCLEIC ACID MOLECULE FOR THE REDUCTION OF PAPD5 AND PAPD7 MRNA FOR THE TREATMENT OF HEPATITIS B INFECTION
US10273474B2 (en) 2012-03-30 2019-04-30 Washington University Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome
WO2019086603A1 (en) 2017-11-03 2019-05-09 Interna Technologies B.V. Mirna molecule, equivalent, antagomir, or source thereof for treating and/or diagnosing a condition and/or a disease associated with neuronal deficiency or for neuronal (re)generation
US10294477B2 (en) 2014-05-01 2019-05-21 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating PKK expression
US10301622B2 (en) 2013-11-04 2019-05-28 Northwestern University Quantification and spatio-temporal tracking of a target using a spherical nucleic acid (SNA)
WO2019116346A1 (en) 2017-12-15 2019-06-20 Novartis Ag Polya tail length analysis of rna by mass spectrometry
WO2019118935A1 (en) 2017-12-14 2019-06-20 Casebia Therapeutics Limited Liability Partnership Novel rna-programmable endonuclease systems and their use in genome editing and other applications
WO2019115416A2 (en) 2017-12-11 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
WO2019122277A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
WO2019122279A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorodithioate internucleoside linkage
WO2019122282A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
WO2019121838A1 (en) 2017-12-21 2019-06-27 F. Hoffmann-La Roche Ag Companion diagnostic for htra1 rna antagonists
US10351853B2 (en) 2014-10-14 2019-07-16 The J. David Gladstone Institutes Compositions and methods for reactivating latent immunodeficiency virus
WO2019140236A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2019138057A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Alpha-synuclein antisense oligonucleotides and uses thereof
WO2019137883A1 (en) 2018-01-10 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
WO2019137974A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating gsk3b expression
WO2019140231A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2019141656A1 (en) 2018-01-17 2019-07-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
WO2019141723A1 (en) 2018-01-18 2019-07-25 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting srebp1
US10365224B2 (en) 2007-12-06 2019-07-30 Genalyte, Inc. Label-free optical sensors
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
WO2019155094A1 (en) 2018-02-12 2019-08-15 Interna Technologies B.V. Anticancer microrna and lipid formulations thereof
WO2019154979A1 (en) 2018-02-09 2019-08-15 Genentech, Inc. Oligonucleotides for modulating tmem106b expression
US10385388B2 (en) 2013-12-06 2019-08-20 Swift Biosciences, Inc. Cleavable competitor polynucleotides
WO2019165067A1 (en) 2018-02-21 2019-08-29 Bristol-Myers Squibb Company Camk2d antisense oligonucleotides and uses thereof
US10400243B2 (en) 2014-11-25 2019-09-03 Ionis Pharmaceuticals, Inc. Modulation of UBE3A-ATS expression
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US10407680B2 (en) 2016-09-29 2019-09-10 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing Tau expression
US10415038B2 (en) 2015-04-03 2019-09-17 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating TMPRSS6 expression
WO2019182037A1 (ja) 2018-03-20 2019-09-26 国立大学法人東京工業大学 毒性が低減されたアンチセンスオリゴヌクレオチド
WO2019183150A1 (en) 2018-03-19 2019-09-26 Casebia Therapeutics Limited Liability Partnership Novel rna-programmable endonuclease systems and uses thereof
WO2019193165A1 (en) 2018-04-05 2019-10-10 F. Hoffmann-La Roche Ag Use of fubp1 inhibitors for treating hepatitis b virus infection
US10443052B2 (en) 2012-10-15 2019-10-15 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
WO2019215065A1 (en) 2018-05-07 2019-11-14 Roche Innovation Center Copenhagen A/S Massively parallel discovery methods for oligonucleotide therapeutics
WO2019217459A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
WO2019215175A1 (en) 2018-05-08 2019-11-14 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
WO2019219723A1 (en) 2018-05-18 2019-11-21 F. Hoffmann-La Roche Ag Pharmaceutical compositions for treatment of microrna related diseases
WO2019224172A1 (en) 2018-05-25 2019-11-28 Roche Innovation Center Copenhagen A/S Novel process for making allofuranose from glucofuranose
US10494633B2 (en) 2015-11-12 2019-12-03 Roche Innovation Center Copenhagen A/S Oligonucleotides for inducing paternal UBE3A expression
WO2019233921A1 (en) 2018-06-05 2019-12-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
WO2019243391A1 (en) 2018-06-21 2019-12-26 F. Hoffmann-La Roche Ag Hybridizing all-lna oligonucleotides
WO2019246112A1 (en) 2018-06-18 2019-12-26 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
WO2019246262A2 (en) 2018-06-21 2019-12-26 University Of Rochester Methods of treating or inhibiting onset of huntington's disease
EP3591054A1 (en) 2013-06-27 2020-01-08 Roche Innovation Center Copenhagen A/S Antisense oligomers and conjugates targeting pcsk9
WO2020007892A1 (en) 2018-07-03 2020-01-09 F. Hoffmann-La Roche Ag Oligonucleotides for modulating tau expression
WO2020007702A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting bcl2l11
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020007700A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting spi1
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011653A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
WO2020011743A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mafb
WO2020011902A1 (en) 2018-07-13 2020-01-16 F. Hoffmann-La Roche Ag Oligonucleotides for modulating rtel1 expression
WO2020011869A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting tlr2
EP3603677A1 (en) 2013-09-13 2020-02-05 Ionis Pharmaceuticals, Inc. Modulators of complement factor b
WO2020025527A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
WO2020025563A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
US10557137B2 (en) 2015-11-06 2020-02-11 Ionis Pharmaceuticals, Inc. Modulating apolipoprotein (a) expression
EP3608406A1 (en) 2014-05-01 2020-02-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
WO2020038968A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
US10577604B2 (en) 2012-10-15 2020-03-03 Ionis Pharmaceuticals, Inc. Methods for monitoring C9ORF72 expression
WO2020043750A1 (en) 2018-08-28 2020-03-05 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
WO2020056341A2 (en) 2018-09-14 2020-03-19 Northwestern University Programming protein polymerization with dna
WO2020069055A1 (en) 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2020086701A1 (en) 2018-10-24 2020-04-30 Codiak Biosciences, Inc. Methods to improve potency of electroporation
WO2020089260A1 (en) 2018-11-01 2020-05-07 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting tia1
WO2020099533A1 (en) 2018-11-16 2020-05-22 F. Hoffmann-La Roche Ag Streptavidin-coated solid phases with a member of a binding pair
WO2020104492A1 (en) 2018-11-22 2020-05-28 Roche Innovation Center Copenhagen A/S Pyridinium salts as activators in the synthesis of stereodefined oligonucleotides
WO2020109343A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Combination therapy for treatment of macular degeneration
WO2020109344A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Occular administration device for antisense oligonucleotides
WO2020118259A1 (en) 2018-12-06 2020-06-11 Northwestern University Protein crystal engineering through dna hybridization interactions
WO2020123663A1 (en) 2018-12-11 2020-06-18 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
WO2020136125A2 (en) 2018-12-21 2020-07-02 Boehringer Ingelheim International Gmbh Antisense oligonucleotides targeting card9
WO2020152303A1 (en) 2019-01-25 2020-07-30 F. Hoffmann-La Roche Ag Lipid vesicle for oral drug delivery
US10738358B2 (en) 2008-09-16 2020-08-11 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
WO2020167822A2 (en) 2019-02-13 2020-08-20 University Of Rochester Gene networks that mediate remyelination of the human brain
WO2020169695A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Phosphonoacetate gapmer oligonucleotides
WO2020169696A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Novel phosphoramidites
WO2020173845A1 (en) 2019-02-26 2020-09-03 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
WO2020178258A1 (en) 2019-03-05 2020-09-10 F. Hoffmann-La Roche Ag Intracellular targeting of molecules
WO2020186059A2 (en) 2019-03-12 2020-09-17 Crispr Therapeutics Ag Novel high fidelity rna-programmable endonuclease systems and uses thereof
WO2020191377A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Extracellular vesicle conjugates and uses thereof
WO2020206115A2 (en) 2019-04-03 2020-10-08 Bristol-Myers Squibb Company Angptl2 antisense oligonucleotides and uses thereof
WO2020203880A1 (ja) 2019-03-29 2020-10-08 田辺三菱製薬株式会社 Ｄｕｘ４の発現を調節するための化合物、方法及び医薬組成物
WO2020201339A1 (en) 2019-04-04 2020-10-08 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
WO2020212301A1 (en) 2019-04-16 2020-10-22 Roche Innovation Center Copenhagen A/S Novel process for preparing nucleotide p(v) monomers
WO2020221705A1 (en) 2019-04-30 2020-11-05 Roche Innovation Center Copenhagen A/S Novel process for preparing rhenium chelated mag3 oligonucleotides
WO2020236600A1 (en) 2019-05-17 2020-11-26 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
WO2020243644A1 (en) 2019-05-31 2020-12-03 Streck, Inc. Detection of antibiotic resistance genes
WO2020245233A1 (en) 2019-06-06 2020-12-10 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2020245377A1 (en) 2019-06-07 2020-12-10 F. Hoffmann-La Roche Ag Hybridizing all-lna oligonucleotides
WO2021011936A2 (en) 2019-07-18 2021-01-21 University Of Rochester Cell-type selective immunoprotection of cells
WO2021020412A1 (ja) 2019-07-30 2021-02-04 塩野義製薬株式会社 Ｍｕｒｆ１を標的とする核酸医薬
US10912792B2 (en) 2015-10-08 2021-02-09 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
WO2021030780A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting cebp/beta
WO2021030769A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with nras antisense oligonucleotides
WO2021030773A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
WO2021030781A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with antisense oligonucleotides targeting kras
WO2021030777A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle linked to molecules and uses thereof
WO2021030776A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting stat6
EP3797860A1 (en) 2016-01-06 2021-03-31 The University of British Columbia Bifurcating mixers and methods of their use and manufacture
WO2021062058A1 (en) 2019-09-25 2021-04-01 Codiak Biosciences, Inc. Sting agonist comprising exosomes for treating neuroimmunological disorders
WO2021075538A1 (ja) 2019-10-18 2021-04-22 第一三共株式会社 二環性ホスホロアミダイトの製造方法
WO2021092145A1 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2021092371A2 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
WO2021108647A1 (en) 2019-11-27 2021-06-03 Crispr Therapeutics Ag Methods of synthesizing rna molecules
EP3835419A1 (en) 2013-12-12 2021-06-16 The Regents of The University of California Methods and compositions for modifying a single stranded target nucleic acid
WO2021119275A1 (en) 2019-12-11 2021-06-17 Intellia Therapeutics, Inc. Modified guide rnas for gene editing
WO2021122910A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sbds inhibitors for treating hepatitis b virus infection
WO2021122921A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of cops3 inhibitors for treating hepatitis b virus infection
WO2021122735A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sept9 inhibitors for treating hepatitis b virus infection
WO2021122993A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of saraf inhibitors for treating hepatitis b virus infection
WO2021123074A1 (en) 2019-12-18 2021-06-24 F. Hoffmann-La Roche Ag Methods of sequencing by synthesis using a consecutive labeling scheme
WO2021122869A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of scamp3 inhibitors for treating hepatitis b virus infection
WO2021123086A1 (en) 2019-12-20 2021-06-24 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for inhibiting scn9a expression
WO2021130266A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
WO2021130270A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv
US11060145B2 (en) 2013-03-13 2021-07-13 Sequenom, Inc. Methods and compositions for identifying presence or absence of hypermethylation or hypomethylation locus
WO2021158810A1 (en) 2020-02-05 2021-08-12 Bristol-Myers Squibb Company Oligonucleotides for splice modulation of camk2d
WO2021170697A1 (en) 2020-02-28 2021-09-02 F. Hoffmann-La Roche Ag Oligonucleotides for modulating cd73 exon 7 splicing
US11111535B2 (en) 2003-06-20 2021-09-07 Qiagen Gmbh Probes, libraries and kits for analysis of mixtures of nucleic acids and methods for constructing the same
WO2021184021A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting pmp22
WO2021184020A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Methods of treating neuroinflammation
WO2021198883A1 (en) 2020-03-31 2021-10-07 Janssen Biopharma, Inc. Synthesis of oligonucleotides and related compounds
US11174470B2 (en) 2019-01-04 2021-11-16 Mammoth Biosciences, Inc. Programmable nuclease improvements and compositions and methods for nucleic acid amplification and detection
WO2021231204A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
WO2021231210A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1r inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021231211A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1s inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021229036A1 (en) 2020-05-13 2021-11-18 F. Hoffmann-La Roche Ag Oligonucleotide agonists targeting progranulin
WO2021230286A1 (ja) 2020-05-12 2021-11-18 田辺三菱製薬株式会社 Ａｔａｘｉｎ ３発現を調節するための化合物、方法及び医薬組成物
WO2021233551A1 (en) 2020-05-22 2021-11-25 F.Hoffmann-La Roche Ag Oligonucleotides for splice modulation of card9
WO2021249993A1 (en) 2020-06-09 2021-12-16 Roche Innovation Center Copenhagen A/S Guanosine analogues for use in therapeutic polynucleotides
WO2021260197A1 (en) 2020-06-26 2021-12-30 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for modulating fubp1 expression
WO2022011214A1 (en) 2020-07-10 2022-01-13 Alnylam Pharmaceuticals, Inc. Circular sirnas
WO2022008935A1 (en) 2020-07-10 2022-01-13 Horizon Discovery Limited Method for producing genetically modified cells
DE212020000516U1 (de) 2019-03-07 2022-01-17 The Regents of the University of California CRISPR-CAS-Effektorpolypeptide
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
WO2022018187A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Oligonucleotides targeting rna binding protein sites
WO2022038211A2 (en) 2020-08-21 2022-02-24 F. Hoffmann-La Roche Ag Use of a1cf inhibitors for treating hepatitis b virus infection
US11261446B2 (en) 2019-03-29 2022-03-01 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating UBE3A-ATS
US11260073B2 (en) 2015-11-02 2022-03-01 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating C90RF72
US11273442B1 (en) 2018-08-01 2022-03-15 Mammoth Biosciences, Inc. Programmable nuclease compositions and methods of use thereof
US11279932B2 (en) 2019-02-27 2022-03-22 Ionis Pharmaceuticals, Inc. Modulators of MALAT1 expression
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
WO2022076596A1 (en) 2020-10-06 2022-04-14 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting stat6
US11332791B2 (en) 2012-07-13 2022-05-17 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
WO2022107025A1 (en) 2020-11-18 2022-05-27 Lemba Bv Umlilo antisense transcription inhibitors
WO2022117747A2 (en) 2020-12-03 2022-06-09 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2022117745A1 (en) 2020-12-03 2022-06-09 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2022122613A1 (en) 2020-12-08 2022-06-16 F. Hoffmann-La Roche Ag Novel synthesis of phosphorodithioate oligonucleotides
US11364304B2 (en) 2016-08-25 2022-06-21 Northwestern University Crosslinked micellar spherical nucleic acids
US11365447B2 (en) 2014-03-13 2022-06-21 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2022129320A1 (en) 2020-12-18 2022-06-23 F. Hoffmann-La Roche Ag Antisense oligonucleotides for targeting progranulin
WO2022136140A1 (en) 2020-12-22 2022-06-30 F. Hoffmann-La Roche Ag Oligonucleotides targeting xbp1
WO2022147214A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2022147223A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
WO2022167456A1 (en) 2021-02-02 2022-08-11 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for inhibiting rtel1 expression
WO2022178180A1 (en) 2021-02-17 2022-08-25 Codiak Biosciences, Inc. Extracellular vesicle linked to a biologically active molecule via an optimized linker and an anchoring moiety
WO2022178149A2 (en) 2021-02-17 2022-08-25 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
EP4056703A1 (en) 2015-03-03 2022-09-14 Ionis Pharmaceuticals, Inc. Methods for modulating mecp2 expression
WO2022192038A1 (en) 2021-03-12 2022-09-15 Northwestern University Antiviral vaccines using spherical nucleic acids
US11447521B2 (en) 2020-11-18 2022-09-20 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
US11453891B2 (en) 2017-05-10 2022-09-27 The Regents Of The University Of California Directed editing of cellular RNA via nuclear delivery of CRISPR/CAS9
WO2022213118A1 (en) 2021-03-31 2022-10-06 Entrada Therapeutics, Inc. Cyclic cell penetrating peptides
WO2022212884A1 (en) 2021-04-01 2022-10-06 Codiak Biosciences, Inc. Extracellular vesicle compositions
WO2022240721A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity
WO2022241408A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating tissue distribution of intracellular therapeutics
WO2022240760A2 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING
WO2022256597A1 (en) 2021-06-04 2022-12-08 Translate Bio, Inc. Assay for quantitative assessment of mrna capping efficiency
EP4101928A1 (en) 2021-06-11 2022-12-14 Bayer AG Type v rna programmable endonuclease systems
WO2022261292A1 (en) 2021-06-10 2022-12-15 Intellia Therapeutics, Inc. Modified guide rnas comprising an internal linker for gene editing
WO2022258555A1 (en) 2021-06-08 2022-12-15 F. Hoffmann-La Roche Ag Oligonucleotide progranulin agonists
WO2022258753A1 (en) 2021-06-11 2022-12-15 Bayer Aktiengesellschaft Type v rna programmable endonuclease systems
US11530409B2 (en) 2016-01-26 2022-12-20 Nissan Chemical Corporation Single-stranded oligonucleotide
WO2022271818A1 (en) 2021-06-23 2022-12-29 Entrada Therapeutics, Inc. Antisense compounds and methods for targeting cug repeats
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
WO2023003922A1 (en) 2021-07-21 2023-01-26 Alnylam Pharmaceuticals, Inc. Metabolic disorder-associated target gene irna compositions and methods of use thereof
WO2023021046A1 (en) 2021-08-16 2023-02-23 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
US11591645B2 (en) 2017-08-31 2023-02-28 Seegene, Inc. Evaluation of performance of components using a pair of dimer-forming primers
EP4144841A1 (en) 2021-09-07 2023-03-08 Bayer AG Novel small rna programmable endonuclease systems with impoved pam specificity and uses thereof
WO2023034817A1 (en) 2021-09-01 2023-03-09 Entrada Therapeutics, Inc. Compounds and methods for skipping exon 44 in duchenne muscular dystrophy
WO2023043280A1 (ko) 2021-09-17 2023-03-23 주식회사 씨젠 합성 비자연 염기를 포함하는 태그 올리고뉴클레오타이드를 이용한 타겟 핵산 서열의 검출
WO2023052317A1 (en) 2021-09-29 2023-04-06 F. Hoffmann-La Roche Ag Rna editing
WO2023064530A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
US11634711B2 (en) 2012-05-17 2023-04-25 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
WO2023078883A1 (en) 2021-11-03 2023-05-11 F. Hoffmann-La Roche Ag Oligonucleotides for modulating apolipoprotein e4 expression
WO2023083906A2 (en) 2021-11-11 2023-05-19 F. Hoffmann-La Roche Ag Pharmaceutical combinations for treatment of hbv
US11667903B2 (en) 2015-11-23 2023-06-06 The Regents Of The University Of California Tracking and manipulating cellular RNA via nuclear delivery of CRISPR/CAS9
WO2023104693A1 (en) 2021-12-07 2023-06-15 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
WO2023111336A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Oligonucleotide gba agonists
WO2023117738A1 (en) 2021-12-20 2023-06-29 F. Hoffmann-La Roche Ag Threose nucleic acid antisense oligonucleotides and methods thereof
WO2023118068A1 (en) 2021-12-23 2023-06-29 Bayer Aktiengesellschaft Novel small type v rna programmable endonuclease systems
WO2023122762A1 (en) 2021-12-22 2023-06-29 Camp4 Therapeutics Corporation Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas
US11690920B2 (en) 2017-07-13 2023-07-04 Northwestern University General and direct method for preparing oligonucleotide-functionalized metal-organic framework nanoparticles
US11708614B2 (en) 2016-06-15 2023-07-25 Streck Llc Assays and methods for determining microbial resistance
WO2023141507A1 (en) 2022-01-20 2023-07-27 Genentech, Inc. Antisense oligonucleotides for modulating tmem106b expression
WO2023150553A1 (en) 2022-02-01 2023-08-10 University Of Rochester Gpr17 promoter-based targeting and transduction of glial progenitor cells
US11732261B2 (en) 2011-08-11 2023-08-22 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
WO2023156652A1 (en) 2022-02-21 2023-08-24 F. Hoffmann-La Roche Ag Antisense oligonucleotide
WO2023217890A1 (en) 2022-05-10 2023-11-16 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting cfp-elk1 intergene region
WO2023220744A2 (en) 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2023222858A1 (en) 2022-05-18 2023-11-23 F. Hoffmann-La Roche Ag Improved oligonucleotides targeting rna binding protein sites
WO2023237587A1 (en) 2022-06-10 2023-12-14 Bayer Aktiengesellschaft Novel small type v rna programmable endonuclease systems
WO2023240277A2 (en) 2022-06-10 2023-12-14 Camp4 Therapeutics Corporation Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas
WO2023242324A1 (en) 2022-06-17 2023-12-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for targeting progranulin
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
EP4332221A1 (en) 2022-08-29 2024-03-06 Roche Innovation Center Copenhagen A/S Threose nucleic acid antisense oligonucleotides and methods thereof
WO2024052403A1 (en) 2022-09-06 2024-03-14 F. Hoffmann-La Roche Ag Double-stranded rna molecule for administration to the eye
WO2024073042A1 (en) 2022-09-30 2024-04-04 Entrada Therapeutics, Inc. Ocular delivery of therapeutic agents
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
US11957788B2 (en) 2014-06-04 2024-04-16 Exicure Operating Company Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
WO2024104914A1 (en) 2022-11-14 2024-05-23 BioNTech SE Rna capping efficiency assay
WO2024119145A1 (en) 2022-12-01 2024-06-06 Camp4 Therapeutics Corporation Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2024126654A1 (en) 2022-12-14 2024-06-20 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b

Families Citing this family (513)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7119184B2 (en) * 1991-08-12 2006-10-10 Isis Pharmaceuticals, Inc. Oligonucleotides having A-DNA form and B-DNA form conformational geometry
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
JP3756313B2 (ja) † 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
EP2341058A3 (en) * 1997-09-12 2011-11-23 Exiqon A/S Oligonucleotide Analogues
JP4148662B2 (ja) * 2000-08-10 2008-09-10 第一三共株式会社 ヌクレオシド及びオリゴヌクレオチド類縁体を含有する核酸試薬及び医薬
US6436640B1 (en) * 1999-03-18 2002-08-20 Exiqon A/S Use of LNA in mass spectrometry
WO2002006297A1 (fr) * 2000-07-19 2002-01-24 Chugai Seiyaku Kabushiki Kaisha Nouveaux derives d'oligonucleotides antisens contre le gene de la tumeur de wilms
JP2002322192A (ja) * 2000-08-10 2002-11-08 Sankyo Co Ltd ２’−ｏ，４’−ｃ−架橋ヌクレオシドトリリン酸体
WO2002028875A2 (en) * 2000-10-04 2002-04-11 Cureon A/S Improved synthesis of purine locked nucleic acid analogues
EP1251183A3 (en) * 2001-04-18 2003-12-10 Exiqon A/S Improved helper probes for detection of a target sequence by a capture oligonucleotide
US20040096880A1 (en) * 2001-08-07 2004-05-20 Kmiec Eric B. Compositions and methods for the treatment of diseases exhibiting protein misassembly and aggregation
WO2003025173A1 (fr) * 2001-09-17 2003-03-27 Takeshi Imanishi Nouveaux derives oligonucleotidiques antisens vis-a-vis du virus de l'hepatite c
US7468244B2 (en) * 2001-09-27 2008-12-23 University Of Delaware Polymorphism detection and separation
US20030207327A1 (en) * 2001-09-27 2003-11-06 Kmiec Eric B. Coisogenic eukaryotic cell collections
AU2002347981A1 (en) * 2001-11-07 2003-05-19 Applera Corporation Universal nucleotides for nucleic acid analysis
US20030198980A1 (en) * 2001-12-21 2003-10-23 Applera Corporation Heteroconfigurational polynucleotides and methods of use
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
US20030166282A1 (en) * 2002-02-01 2003-09-04 David Brown High potency siRNAS for reducing the expression of target genes
WO2003064625A2 (en) 2002-02-01 2003-08-07 Sequitur, Inc. Oligonucleotide compositions with enhanced efficiency
US7615619B2 (en) 2002-02-13 2009-11-10 Takeshi Imanishi Nucleoside analogues and oligonucleotide derivative comprising nucleotide analogue thereof
US20030198960A1 (en) * 2002-04-01 2003-10-23 Wenhong Fan Signal amplifying targeted reporters for biological and chemical sensor applications
US7211382B2 (en) * 2002-04-09 2007-05-01 Orchid Cellmark Inc. Primer extension using modified nucleotides
AU2003243541A1 (en) * 2002-06-12 2003-12-31 Ambion, Inc. Methods and compositions relating to labeled rna molecules that reduce gene expression
US20100075423A1 (en) * 2002-06-12 2010-03-25 Life Technologies Corporation Methods and compositions relating to polypeptides with rnase iii domains that mediate rna interference
US20040248094A1 (en) * 2002-06-12 2004-12-09 Ford Lance P. Methods and compositions relating to labeled RNA molecules that reduce gene expression
US20040175722A1 (en) * 2002-10-07 2004-09-09 Kmiec Eric B. Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration
TWI347948B (en) 2002-11-19 2011-09-01 Sankyo Co Novel 2',5'-oligoadenylic acid compositions
JP5132025B2 (ja) * 2002-11-19 2013-01-30 第一三共株式会社 新規２’，５’−オリゴアデニル酸類縁体
AU2004276722B2 (en) 2003-05-19 2009-03-12 Gen-Probe Incorporated Compositions, methods and kits for determining the presence of trichomonas vaginalis in a test sample
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
US7906639B2 (en) 2003-11-07 2011-03-15 Sankyo Company, Limited Oligonucleotides having a 2′-O,4′-C-ethylene nucleotide in the third position of the 3′-end
US7972783B2 (en) * 2003-11-24 2011-07-05 Branhaven LLC Method and markers for determining the genotype of horned/polled cattle
US7713697B2 (en) * 2004-08-27 2010-05-11 Gen-Probe Incorporated Methods and kits for amplifying DNA
CA2898814C (en) * 2004-08-27 2015-12-29 Gen-Probe Incorporated Single-primer nucleic acid amplification methods
US20060073506A1 (en) 2004-09-17 2006-04-06 Affymetrix, Inc. Methods for identifying biological samples
US20060073511A1 (en) 2004-10-05 2006-04-06 Affymetrix, Inc. Methods for amplifying and analyzing nucleic acids
US7682782B2 (en) 2004-10-29 2010-03-23 Affymetrix, Inc. System, method, and product for multiple wavelength detection using single source excitation
WO2006059507A1 (ja) * 2004-11-30 2006-06-08 Sankyo Company, Limited 11β-HSD1アンチセンス化合物
US20060166238A1 (en) * 2004-12-22 2006-07-27 Ramsing Niels B Probes, libraries and kits for analysis of mixtures of nucleic acids and methods for constructing the same
US20060142228A1 (en) * 2004-12-23 2006-06-29 Ambion, Inc. Methods and compositions concerning siRNA's as mediators of RNA interference
EP2233582A1 (en) 2005-02-01 2010-09-29 AB Advanced Genetic Analysis Corporation Nucleic acid sequencing by performing successive cycles of duplex extension
CA2596496A1 (en) 2005-02-01 2006-08-10 Agencourt Bioscience Corp. Reagents, methods, and libraries for bead-based sequencing
US20070065840A1 (en) * 2005-03-23 2007-03-22 Irena Naguibneva Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS
JP4741328B2 (ja) * 2005-09-08 2011-08-03 クラリオン株式会社 ナビゲーション装置
EP1960536B1 (en) 2005-11-30 2013-06-26 St. Anna Kinderkrebsforschung Detection of fungi
EP3000480A1 (en) 2005-12-01 2016-03-30 ProNAi Therapeutics, Inc. Cancer therapies and pharmaceutical compositions used therein
CN101437933B (zh) 2005-12-28 2013-11-06 斯克里普斯研究所 作为药物靶标的天然反义和非编码的rna转录物
EP1966390A1 (en) * 2005-12-29 2008-09-10 Exiqon A/S Detection of tissue origin of cancer
WO2007089584A2 (en) 2006-01-26 2007-08-09 Isis Pharmaceuticals, Inc. Compositions and their uses directed to huntingtin
JP5342881B2 (ja) 2006-01-27 2013-11-13 アイシス ファーマシューティカルズ， インコーポレーテッド ６−修飾された二環式核酸類似体
EP2007907A2 (en) * 2006-04-19 2008-12-31 Applera Corporation Reagents, methods, and libraries for gel-free bead-based sequencing
AU2007249349B2 (en) * 2006-05-11 2012-03-08 Isis Pharmaceuticals, Inc. 5'-Modified bicyclic nucleic acid analogs
US7666854B2 (en) * 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
US20090023221A1 (en) * 2006-05-19 2009-01-22 Exigon A/S Oligonucleotide probes useful for detection and analysis of microrna precursors
JP5152929B2 (ja) 2006-06-06 2013-02-27 ジェン−プロウブ インコーポレイテッド 核酸増幅法におけるタグ化オリゴヌクレオチドおよびその使用
US20080076674A1 (en) * 2006-07-06 2008-03-27 Thomas Litman Novel oligonucleotide compositions and probe sequences useful for detection and analysis of non coding RNAs associated with cancer
US8198253B2 (en) 2006-07-19 2012-06-12 Isis Pharmaceuticals, Inc. Compositions and their uses directed to HBXIP
EP2057465A4 (en) 2006-08-09 2010-04-21 Homestead Clinical Corp SPECIFIC ORGAN PROTEINS AND METHODS OF USE
US9074205B2 (en) * 2006-10-18 2015-07-07 Marina Biotech, Inc. Nicked or gapped nucleic acid molecules and uses thereof
EP2113567B1 (en) 2006-12-21 2019-04-03 QIAGEN GmbH MicroRNA target site blocking oligos and uses thereof
US20100292301A1 (en) * 2007-02-28 2010-11-18 Elena Feinstein Novel sirna structures
US8183359B2 (en) * 2007-03-01 2012-05-22 Gen-Probe Incorporated Kits for amplifying DNA
CA2679867A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof
WO2008109362A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf gene expression and uses thereof
JP2010519908A (ja) * 2007-03-02 2010-06-10 エムディーアールエヌエー，インコーポレイテッド Ｈｉｆ１ａ遺伝子の発現を抑制するための核酸化合物およびその使用
WO2008109449A1 (en) * 2007-03-02 2008-09-12 Mdrna Inc. Nucleic acid compounds for inhibiting bcl2 gene expression and uses thereof
CA2679244A1 (en) * 2007-03-02 2009-03-05 Mdrna, Inc. Nucleic acid compounds for inhibiting myc gene expression and uses thereof
US20080293136A1 (en) * 2007-03-02 2008-11-27 Nastech Pharmaceutical Company Inc. Nucleic acid compounds for inhibiting akt gene expression and uses thereof
WO2008109357A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting apob gene expression and uses thereof
US20100105134A1 (en) * 2007-03-02 2010-04-29 Mdrna, Inc. Nucleic acid compounds for inhibiting gene expression and uses thereof
US20100112687A1 (en) * 2007-03-02 2010-05-06 Mdrna, Inc. Nucleic acid compounds for inhibiting erbb family gene expression and uses thereof
JP2010519913A (ja) * 2007-03-02 2010-06-10 エムディーアールエヌエー，インコーポレイテッド Ｗｎｔ遺伝子の発現を抑制するための核酸化合物およびその使用
MX2009009530A (es) * 2007-03-07 2010-05-19 Nventa Biopharmaceuticals Corp Composiciones de acidos nucleicos cerrados bicatenarios.
WO2008111908A1 (en) * 2007-03-15 2008-09-18 Jyoti Chattopadhyaya Five- and six-membered conformationally locked 2',4'- carbocyclic ribo-thymidines for the treatment of infections and cancer
EP1978111B1 (en) 2007-04-02 2013-03-27 Gen-Probe Incorporated Compositions, kits and related methods for the detection and/or monitoring of Pseudomonas aeruginosa
FR2915208A1 (fr) 2007-04-20 2008-10-24 Millipore Corp Composition comprenant l'association d'edta et de pei pour augmenter la permeabilite des parois des microorganismes et utilisations de ladite composition
US8278425B2 (en) 2007-05-30 2012-10-02 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
WO2008151631A2 (en) * 2007-06-15 2008-12-18 Exiqon A/S Use of short oligonucleotides for reagent redundancy experiments in rna functional analysis
CN101796062B (zh) * 2007-07-05 2014-07-30 Isis制药公司 6-双取代双环核酸类似物
DK2548962T3 (en) 2007-09-19 2016-04-11 Applied Biosystems Llc Sirna sequence-independent modification formats to reduce off-target phenotype effects in RNAI and stabilized forms thereof
JP5404638B2 (ja) * 2007-11-07 2014-02-05 ザ ユニヴァーシティ オブ ブリティッシュ コロンビア マイクロ流体デバイスおよびその使用方法
WO2009067632A1 (en) * 2007-11-20 2009-05-28 Applied Biosystems Inc. Method of sequencing nucleic acids using elaborated nucleotide phosphorothiolate compounds
WO2009067647A1 (en) * 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
WO2009074990A2 (en) * 2007-12-12 2009-06-18 Quark Pharmaceuticals, Inc. Rtp801l sirna compounds and methods of use thereof
US8614311B2 (en) 2007-12-12 2013-12-24 Quark Pharmaceuticals, Inc. RTP801L siRNA compounds and methods of use thereof
JP5498954B2 (ja) 2007-12-21 2014-05-21 ジェン−プロウブ インコーポレイテッド 抗生剤耐性微生物の検出
EP2242854A4 (en) * 2008-01-15 2012-08-15 Quark Pharmaceuticals Inc COMPOUNDS AND USES THEREOF
US8530640B2 (en) * 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
US20090215050A1 (en) * 2008-02-22 2009-08-27 Robert Delmar Jenison Systems and methods for point-of-care amplification and detection of polynucleotides
CA2718765A1 (en) * 2008-03-20 2009-09-24 Quark Pharmaceuticals, Inc. Novel sirna compounds for inhibiting rtp801
EP2285819B1 (en) * 2008-04-04 2013-10-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
US20090326049A1 (en) * 2008-04-04 2009-12-31 Alexander Aristarkhov Blocking oligos for inhibition of microrna and sirna activity and uses thereof
US20100113284A1 (en) * 2008-04-04 2010-05-06 Alexander Aristarkhov Small interfering rna (sirna) target site blocking oligos and uses thereof
EP2285385A4 (en) * 2008-04-15 2013-01-16 Quark Pharmaceuticals Inc COMPOUNDS BASED ON RNSI TO INHIBIT NRF2
CA2723726C (en) 2008-05-13 2017-09-12 Michael M. Becker Inactivatable target capture oligomers for use in the selective hybridization and capture of target nucleic acid sequences
AU2009262870B2 (en) 2008-05-30 2014-03-20 Gen-Probe Incorporated Compositions, kits and related methods for the detection and/or monitoring of Salmonella
DK2356129T3 (da) * 2008-09-24 2013-05-13 Isis Pharmaceuticals Inc Substituerede alpha-L-bicykliske nukleosider
RU2604489C2 (ru) 2008-10-03 2016-12-10 КьюРНА,Инк.,US Лечение заболеваний, связанных с аполипопротеином-а1, путем ингибирования природного антисмыслового транскрипта аполипопротеина-а1
MX2011005918A (es) 2008-12-04 2011-06-17 Opko Curna Llc Tratamiento de enfermedades relacionadas con un gen supresor de tumor mediante inhibicion del transcrito antisentido natural para el gen.
US8927511B2 (en) 2008-12-04 2015-01-06 Curna, Inc. Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF
ES2629630T3 (es) 2008-12-04 2017-08-11 Curna, Inc. Tratamiento de enfermedades relacionadas con eritropoyetina (EPO) mediante inhibición del transcrito antisentido natural a EPO
EP2910647A1 (en) 2008-12-30 2015-08-26 Gen-Probe Incorporated Compositions, kits and related methods for the detection and/or monitoring of listeria
CA2752237C (en) 2009-02-12 2020-03-24 Opko Curna, Llc Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf
US8921039B2 (en) 2009-02-26 2014-12-30 Gen-Probe Incorporated Assay for detection of human parvovirus nucleic acid
CA2755409C (en) 2009-03-16 2019-04-30 Joseph Collard Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2
CA2755404C (en) 2009-03-17 2020-03-24 Joseph Collard Treatment of delta-like 1 homolog (dlk1) related diseases by inhibition of natural antisense transcript to dlk1
US8481698B2 (en) * 2009-03-19 2013-07-09 The President And Fellows Of Harvard College Parallel proximity ligation event analysis
WO2010126913A1 (en) 2009-04-27 2010-11-04 Gen-Probe Incorporated Methods and kits for use in the selective amplification of target sequences
CN103223177B (zh) 2009-05-06 2016-08-10 库尔纳公司 通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病
CA2761142C (en) 2009-05-06 2021-06-08 Opko Curna, Llc Treatment of tristetraproline (ttp) related diseases by inhibition of natural antisense transcript to ttp
US9012139B2 (en) 2009-05-08 2015-04-21 Curna, Inc. Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to DMD family
CN102575251B (zh) 2009-05-18 2018-12-04 库尔纳公司 通过抑制针对重编程因子的天然反义转录物来治疗重编程因子相关的疾病
US8895527B2 (en) 2009-05-22 2014-11-25 Curna, Inc. Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2(IRS2) related diseases by inhibition of natural antisense transcript to TFE3
CA2764683A1 (en) 2009-05-28 2010-12-02 Joseph Collard Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene
ES2620960T3 (es) 2009-06-16 2017-06-30 Curna, Inc. Tratamiento de enfermedades relacionadas con un gen de colágeno mediante la inhibición de un transcrito antisentido natural a un gen de colágeno
JP6128846B2 (ja) 2009-06-16 2017-05-17 クルナ・インコーポレーテッド パラオキソナーゼ（ｐｏｎ１）に対する天然アンチセンス転写物の抑制によるｐｏｎ１遺伝子関連疾患の治療
JP6073133B2 (ja) 2009-06-24 2017-02-01 クルナ・インコーポレーテッド 腫瘍壊死因子受容体２（ｔｎｆｒ２）に対する天然アンチセンス転写物の抑制によるｔｎｆｒ２関連疾患の治療
WO2010151674A2 (en) 2009-06-26 2010-12-29 Curna, Inc. Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene
JP2011024434A (ja) 2009-07-22 2011-02-10 Galaxy Pharma Inc オリゴヌクレオチドのスクリーニング方法及びオリゴヌクレオチドライブラリー
KR101801407B1 (ko) 2009-07-24 2017-11-24 큐알엔에이, 인크. 시르투인 (ｓｉｒｔ)에 대한 천연 안티센스 전사체의 억제에 의한 시르투인 관련된 질환의 치료
WO2011012136A1 (en) 2009-07-28 2011-02-03 Exiqon A/S A method for classifying a human cell sample as cancerous
KR101802536B1 (ko) 2009-08-05 2017-11-28 큐알엔에이, 인크. 인슐린 유전자 (ｉｎｓ)에 대한 자연 안티센스 전사체의 저해에 의한 인슐린 유전자 (ｉｎｓ) 관련된 질환의 치료
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
WO2011019815A2 (en) 2009-08-11 2011-02-17 Curna, Inc. Treatment of adiponectin (adipoq) related diseases by inhibition of natural antisense transcript to an adiponectin (adipoq)
JP5943836B2 (ja) 2009-08-21 2016-07-05 カッパーアールエヌエー，インコーポレイテッド ‘ｈｓｐ７０相互作用タンパク質ｃ末端’（ｃｈｉｐ）に対する天然アンチセンス転写産物の阻害によるｃｈｉｐ関連疾患の治療
JP5964232B2 (ja) 2009-08-25 2016-08-03 カッパーアールエヌエー，インコーポレイテッド ‘ｉｑモチーフ含有ｇｔｐアーゼ活性化タンパク質’（ｉｑｇａｐ）に対する天然アンチセンス転写産物の阻害によるｉｑｇａｐ関連疾患の治療
US20110196141A1 (en) * 2009-09-07 2011-08-11 Council Of Scientific & Industrial Research Locked and unlocked 2'-o phosphoramidite nucleosides, process of preparation thereof and oligomers comprising the nucleosides
JP6175236B2 (ja) 2009-09-25 2017-08-09 カッパーアールエヌエー，インコーポレイテッド フィラグリン（ｆｌｇ）の発現および活性の調整によるｆｌｇ関連疾患の処置
US20150025122A1 (en) 2009-10-12 2015-01-22 Larry J. Smith Methods and Compositions for Modulating Gene Expression Using Oligonucleotide Based Drugs Administered in vivo or in vitro
DK2513310T3 (en) 2009-12-16 2018-02-05 Curna Inc TREATMENT OF DISEASES CONNECTED WITH MEMBRANE-BONDED TRANSCRIPTION FACTOR Peptidase, site 1 (MBTPS1), BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTION TO MBTPS1
WO2011087789A2 (en) 2009-12-22 2011-07-21 Becton, Dickinson And Company Methods for the detection of microorganisms
EP2515947B1 (en) 2009-12-23 2021-10-06 CuRNA, Inc. Treatment of uncoupling protein 2 (ucp2) related diseases by inhibition of natural antisense transcript to ucp2
DK2516648T3 (en) 2009-12-23 2018-02-12 Curna Inc TREATMENT OF HEPATOCYTE GROWTH FACTOR (HGF) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT AGAINST HGF
JP2011130725A (ja) * 2009-12-25 2011-07-07 Contig I:Kk Ｌｎａオリゴヌクレオチドとそれを含有する化粧品
JP5993744B2 (ja) 2009-12-29 2016-09-14 カッパーアールエヌエー，インコーポレイテッド 核呼吸因子１（ｎｒｆ１）に対する天然アンチセンス転写物の阻害による核呼吸因子１関連疾患の治療
EP2519634B1 (en) 2009-12-29 2016-06-01 CuRNA, Inc. TREATMENT OF TUMOR PROTEIN 63 (p63) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO p63
US20120289583A1 (en) 2009-12-31 2012-11-15 Curna, Inc. Treatment of insulin receptor substrate 2 (irs2) related diseases by inhibition of natural antisense transcript to irs2 and transcription factor e3 (tfe3)
EP2521784B1 (en) 2010-01-04 2017-12-06 CuRNA, Inc. Treatment of interferon regulatory factor 8 (irf8) related diseases by inhibition of natural antisense transcript to irf8
EP2521785B1 (en) 2010-01-06 2022-03-09 CuRNA, Inc. Inhibition of natural antisense transcript to a pancreatic developmental gene for use in a treatment of pancreatic developmental gene related diseases
ES2664866T3 (es) 2010-01-11 2018-04-23 Curna, Inc. Tratamiento de enfermedades relacionadas con la globulina fijadora de hormonas sexuales (shbg) mediante inhibición del transcrito antisentido natural a shbg
WO2011085102A1 (en) 2010-01-11 2011-07-14 Isis Pharmaceuticals, Inc. Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2011088148A1 (en) * 2010-01-12 2011-07-21 Isis Pharmaceuticals, Inc. Modulation of transforming growth factor-beta 1 expression
DK2529015T3 (en) 2010-01-25 2018-02-26 Curna Inc TREATMENT OF RNASE H1-RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO RNASE H1
CA2790506A1 (en) 2010-02-22 2011-08-25 Curna, Inc. Treatment of pyrroline-5-carboxylate reductase 1 (pycr1) related diseases by inhibition of natural antisense transcript to pycr1
WO2011106689A1 (en) * 2010-02-26 2011-09-01 Isis Pharmaceuticals, Inc. Modulation of smad3 expression
ES2743600T3 (es) 2010-03-12 2020-02-20 Brigham & Womens Hospital Inc Métodos de tratamiento de los trastornos inflamatorios vasculares
US9193752B2 (en) 2010-03-17 2015-11-24 Isis Pharmaceuticals, Inc. 5′-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2011120023A1 (en) 2010-03-26 2011-09-29 Marina Biotech, Inc. Nucleic acid compounds for inhibiting survivin gene expression uses thereof
CA2795145C (en) 2010-04-02 2019-01-22 Curna, Inc. Treatment of colony-stimulating factor 3 (csf3) related diseases by inhibition of natural antisense transcript to csf3
EP4385568A2 (en) 2010-04-06 2024-06-19 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of cd274/pd-l1 gene
TWI644675B (zh) 2010-04-09 2018-12-21 可娜公司 藉由抑制纖維母細胞生長因子２１（ｆｇｆ２１）之天然反義轉錄物以治療ｆｇｆ２１相關疾病
WO2011133584A2 (en) 2010-04-19 2011-10-27 Marina Biotech, Inc. Nucleic acid compounds for inhibiting hras gene expression and uses thereof
WO2011139710A1 (en) 2010-04-26 2011-11-10 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
US8278049B2 (en) 2010-04-26 2012-10-02 Ann & Robert H. Lurie Children's Hospital of Chicago Selective enrichment of CpG islands
WO2011139842A2 (en) 2010-04-28 2011-11-10 Marina Biotech, Inc. Nucleic acid compounds for inhibiting fgfr3 gene expression and uses thereof
KR20130101442A (ko) 2010-05-03 2013-09-13 큐알엔에이, 인크. 시르투인 (sirt)에 대한 자연 안티센스 전사체의 저해에 의한 시르투인 (sirt) 관련된 질환의 치료
TWI531370B (zh) 2010-05-14 2016-05-01 可娜公司 藉由抑制ｐａｒ４天然反股轉錄本治療ｐａｒ４相關疾病
RU2620978C2 (ru) 2010-05-26 2017-05-30 Курна, Инк. Лечение заболеваний, связанных с метионинсульфоксидредуктазой а (msra), путем ингибирования природного антисмыслового транскрипта гена msra
JP5973996B2 (ja) 2010-05-26 2016-08-23 カッパーアールエヌエー，インコーポレイテッド Ａｔｏｈ１に対する天然アンチセンス転写物の阻害による無調ホモログ１（ａｔｏｈ１）関連疾患の治療
CA2801066C (en) 2010-06-02 2021-02-09 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
EP2582397A4 (en) 2010-06-15 2014-10-29 Isis Pharmaceuticals Inc COMPOUNDS AND METHODS FOR MODULATING THE INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS
RU2016118528A (ru) 2010-06-23 2018-10-31 Курна, Инк. Лечение заболеваний, связанных с альфа-субъединицей потенциалзависимого натриевого канала (scna), путем ингибирования природного антисмыслового транскрипта гена scna
AU2011272868B2 (en) 2010-06-30 2015-09-17 Gen-Probe Incorporated Method and apparatus for identifying analyte-containing samples using single-read determination of analyte and process control signals
WO2012006551A2 (en) 2010-07-08 2012-01-12 The Brigham And Women's Hospital, Inc. Neuroprotective molecules and methods of treating neurological disorders and inducing stress granules
RU2611190C2 (ru) 2010-07-14 2017-02-21 Курна, Инк. Лечение заболеваний, связанных с геном dlg, путем ингибирования природного антисмыслового транскрипта гена dlg
US9081737B2 (en) 2010-08-02 2015-07-14 Integrated Dna Technologies, Inc. Methods for predicting stability and melting temperatures of nucleic acid duplexes
US8993533B2 (en) 2010-10-06 2015-03-31 Curna, Inc. Treatment of sialidase 4 (NEU4) related diseases by inhibition of natural antisense transcript to NEU4
WO2012048113A2 (en) 2010-10-07 2012-04-12 The General Hospital Corporation Biomarkers of cancer
US8648053B2 (en) 2010-10-20 2014-02-11 Rosalind Franklin University Of Medicine And Science Antisense oligonucleotides that target a cryptic splice site in Ush1c as a therapeutic for Usher syndrome
US9222088B2 (en) 2010-10-22 2015-12-29 Curna, Inc. Treatment of alpha-L-iduronidase (IDUA) related diseases by inhibition of natural antisense transcript to IDUA
WO2012064758A2 (en) 2010-11-08 2012-05-18 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
JP6336755B2 (ja) 2010-11-12 2018-06-06 ザ ジェネラル ホスピタル コーポレイション ポリコームに関連する非コードｒｎａ
US10000752B2 (en) 2010-11-18 2018-06-19 Curna, Inc. Antagonat compositions and methods of use
WO2012068519A2 (en) 2010-11-19 2012-05-24 Sirius Genomics Inc. Markers associated with response to activated protein c administration, and uses thereof
KR102010598B1 (ko) 2010-11-23 2019-08-13 큐알엔에이, 인크. Nanog에 대한 자연 안티센스 전사체의 저해에 의한 nanog 관련된 질환의 치료
US9193973B2 (en) 2010-12-10 2015-11-24 Alynylam Pharmaceuticals, Inc. Compositions and methods for increasing erythropoietin (EPO) production
EP2648763A4 (en) 2010-12-10 2014-05-14 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR EXPRESSION INHIBITION OF GENES KLF-1 AND BCL11A
AR084319A1 (es) 2010-12-15 2013-05-08 Miragen Therapeutics INHIBIDORES DE microARN (miARN O miR) QUE COMPRENDEN NUCLEOTIDOS BLOQUEADOS
US9045749B2 (en) 2011-01-14 2015-06-02 The General Hospital Corporation Methods targeting miR-128 for regulating cholesterol/lipid metabolism
KR102481317B1 (ko) 2011-03-29 2022-12-26 알닐람 파마슈티칼스 인코포레이티드 Tmprss6 유전자의 발현을 억제하기 위한 조성물 및 방법
CN103547588B (zh) 2011-04-13 2016-06-29 Isis制药公司 Ptp1b表达的反义调节
US9353371B2 (en) 2011-05-02 2016-05-31 Ionis Pharmaceuticals, Inc. Antisense compounds targeting genes associated with usher syndrome
CN103620036B (zh) 2011-06-09 2016-12-21 库尔纳公司 通过抑制共济蛋白(fxn)的天然反义转录物而治疗fxn 相关疾病
US9187749B2 (en) 2011-06-10 2015-11-17 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
ES2923573T3 (es) 2011-06-21 2022-09-28 Alnylam Pharmaceuticals Inc Composiciones de ARNi de proteína 3 de tipo angiopoyetina (ANGPTL3) y métodos de uso de las mismas
WO2012178033A2 (en) 2011-06-23 2012-12-27 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
KR20140147797A (ko) 2011-06-27 2014-12-30 더 잭슨 래보라토리 암 및 자가면역 질환의 치료 방법 및 조성물
EP2739735A2 (en) 2011-08-01 2014-06-11 Alnylam Pharmaceuticals, Inc. Method for improving the success rate of hematopoietic stem cell transplants
EP3640332A1 (en) 2011-08-29 2020-04-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
WO2013033223A1 (en) 2011-08-29 2013-03-07 Isis Pharmaceuticals, Inc. Methods and compounds useful in conditions related to repeat expansion
EA029151B1 (ru) 2011-09-06 2018-02-28 Курна, Инк. ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С АЛЬФА-СУБЪЕДИНИЦАМИ ПОТЕНЦИАЛЗАВИСИМЫХ НАТРИЕВЫХ КАНАЛОВ (SCNxA), С ПОМОЩЬЮ МАЛЫХ МОЛЕКУЛ
US9175337B2 (en) 2011-09-21 2015-11-03 Gen-Probe Incorporated Methods for amplifying nucleic acid using tag-mediated displacement
CA2851280C (en) 2011-10-11 2021-05-18 The Brigham And Women's Hospital, Inc. Micrornas in neurodegenerative disorders
WO2013067050A1 (en) 2011-10-31 2013-05-10 University Of Utah Research Foundation Genetic alterations in glioblastoma
US9243291B1 (en) 2011-12-01 2016-01-26 Isis Pharmaceuticals, Inc. Methods of predicting toxicity
JP6112569B2 (ja) 2011-12-16 2017-04-12 国立大学法人 東京医科歯科大学 キメラ２重鎖核酸
KR20140102759A (ko) 2011-12-16 2014-08-22 모더나 세라퓨틱스, 인코포레이티드 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물
WO2013106770A1 (en) 2012-01-11 2013-07-18 Isis Pharmaceuticals, Inc. Compositions and methods for modulation of ikbkap splicing
HUE040179T2 (hu) 2012-03-15 2019-02-28 Curna Inc Agyi eredetû neutrotróf faktorral (Brain-derived neurotrophic factor, BDNF) összefüggõ betegségek kezelése a BDNF-fel kapcsolatos természetes antiszensz transzkriptumok gátlása révén
JP6124986B2 (ja) 2012-03-19 2017-05-10 ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドＴｈｅ Ｂｒｉｇｈａｍ ａｎｄ Ｗｏｍｅｎ’ｓ Ｈｏｓｐｉｔａｌ， Ｉｎｃ． 拡張期心不全を処置するための増殖分化因子（ｇｄｆ）
EP2833892A4 (en) 2012-04-02 2016-07-20 Moderna Therapeutics Inc MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF PROTEINS AND PEPTIDES ASSOCIATED WITH ONCOLOGY
WO2013151666A2 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of biologics and proteins associated with human disease
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
WO2013181666A2 (en) 2012-06-01 2013-12-05 Isis Pharmaceuticals, Inc. Antisense compounds targeting genes associated with fibronectin
US9828602B2 (en) 2012-06-01 2017-11-28 Ionis Pharmaceuticals, Inc. Antisense compounds targeting genes associated with fibronectin
WO2013184209A1 (en) 2012-06-04 2013-12-12 Ludwig Institute For Cancer Research Ltd. Mif for use in methods of treating subjects with a neurodegenerative disorder
CA2876180C (en) 2012-06-21 2019-11-19 MiRagen Therapeutics, Inc. Oligonucleotide-based inhibitors comprising locked nucleic acid motif
AU2013202793B2 (en) 2012-07-31 2014-09-18 Gen-Probe Incorporated System, method and apparatus for automated incubation
WO2014051076A1 (ja) 2012-09-28 2014-04-03 株式会社Ｂｎａ Ｂｎａクランプ法
CA2887884A1 (en) 2012-10-12 2014-04-17 Isis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
WO2014059341A2 (en) 2012-10-12 2014-04-17 Isis Pharmaceuticals, Inc. Antisense compounds and uses thereof
US10723754B2 (en) 2012-10-22 2020-07-28 Idenix Pharmaceuticals Llc 2′,4′-bridged nucleosides for HCV infection
WO2014071358A2 (en) 2012-11-05 2014-05-08 Foundation Medicine, Inc. Novel ntrk1 fusion molecules and uses thereof
US20150299803A1 (en) 2012-11-05 2015-10-22 Pronai Therapeutics, Inc. Methods of Using Biomarkers for the Treatment of Cancer by Modulation of BCL2 Expression
JP6144355B2 (ja) 2012-11-26 2017-06-07 モデルナティエックス インコーポレイテッドＭｏｄｅｒｎａＴＸ，Ｉｎｃ． 化学修飾ｍＲＮＡ
WO2014093537A1 (en) 2012-12-11 2014-06-19 Isis Pharmaceuticals, Inc. Competitive modulation of micrornas
JP2016504050A (ja) 2013-01-17 2016-02-12 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 細胞表現型の改変のためのシグナルセンサーポリヌクレオチド
CA2898326C (en) 2013-01-18 2022-05-17 Foundation Medicine, Inc. Methods of treating cholangiocarcinoma
EP3778618A1 (en) 2013-02-04 2021-02-17 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
WO2014130922A1 (en) 2013-02-25 2014-08-28 Trustees Of Boston University Compositions and methods for treating fungal infections
US20160108395A1 (en) 2013-03-01 2016-04-21 National University Corporation Tokyo Medical And Dental University Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent
WO2014159813A1 (en) 2013-03-13 2014-10-02 Moderna Therapeutics, Inc. Long-lived polynucleotide molecules
US9273349B2 (en) 2013-03-14 2016-03-01 Affymetrix, Inc. Detection of nucleic acids
WO2014152211A1 (en) 2013-03-14 2014-09-25 Moderna Therapeutics, Inc. Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions
SI2970974T1 (sl) 2013-03-14 2017-12-29 Alnylam Pharmaceuticals, Inc. Komplementarna komponenta C5 sestavkov IRNA in postopki njene uporabe
EP2971160B1 (en) 2013-03-15 2018-05-30 Bio-Rad Laboratories, Inc. Digital assays for mutation detection
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
KR20150131365A (ko) 2013-03-15 2015-11-24 미라젠 세러퓨틱스 인코포레이티드 브리지드 바이사이클릭 뉴클레오시드
US9752143B2 (en) 2013-03-15 2017-09-05 MiRagen Therapeutics, Inc. Locked nucleic acid inhibitor of miR-145 and uses thereof
US10092627B2 (en) 2013-04-08 2018-10-09 President And Fellows Of Harvard College Methods and compositions for rejuvenating skeletal muscle stem cells
US10590412B2 (en) 2013-04-19 2020-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation nucleic acids through nonsense mediated decay
IL293657A (en) 2013-05-22 2022-08-01 Alnylam Pharmaceuticals Inc Preparations of tmprss6 irna and methods of using them
CN113018307A (zh) 2013-05-22 2021-06-25 阿尔尼拉姆医药品有限公司 SERPINA1 iRNA组合物及其使用方法
AU2014272526A1 (en) 2013-05-30 2015-12-10 National University Corporation Tokyo Medical And Dental University Double-stranded agents for delivering therapeutic oligonucleotides
EP3004396B1 (en) 2013-06-06 2019-10-16 The General Hospital Corporation Compositions for the treatment of cancer
US20160220640A1 (en) 2013-06-11 2016-08-04 The Brigham And Women's Hospital, Inc. Methods and compositions for increasing neurogenesis and angiogenesis
CA2915443A1 (en) 2013-06-16 2014-12-24 National University Corporation Tokyo Medical And Dental University Double-stranded antisense nucleic acid with exon-skipping effect
AU2014284152B2 (en) 2013-06-21 2020-01-23 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
EP3971287A1 (en) 2013-07-11 2022-03-23 ModernaTX, Inc. Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use
WO2015009731A2 (en) 2013-07-15 2015-01-22 The Regents Of The University Of California Azacyclic constrained analogs of fty720
US10435430B2 (en) 2013-07-31 2019-10-08 Ionis Pharmaceuticals, Inc. Methods and compounds useful in conditions related to repeat expansion
PL3041854T3 (pl) 2013-08-08 2020-06-29 The Scripps Research Institute Sposób miejscowo specyficznego oznakowania enzymatycznego kwasów nukleinowych in vitro przez inkorporację niewystępujących naturalnie nukleotydów
WO2015023503A2 (en) 2013-08-14 2015-02-19 Primeradx, Inc. Compositions and methods for multimodal analysis of cmet nucleic acids
KR20160106041A (ko) 2013-08-14 2016-09-09 퀴아젠 맨스필드, 인코퍼레이티드 Ｎｒａｓ 및 ｂｒａｆ 핵산의 멀티플렉스 분석을 위한 조성물 및 방법
AU2014315287A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Chimeric polynucleotides
US20160194368A1 (en) 2013-09-03 2016-07-07 Moderna Therapeutics, Inc. Circular polynucleotides
WO2015042447A1 (en) 2013-09-20 2015-03-26 Isis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
EP3052626A1 (en) 2013-10-02 2016-08-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
PL3052628T3 (pl) 2013-10-04 2020-08-24 Alnylam Pharmaceuticals, Inc. Kompozycje i sposoby hamowania ekspresji genu ALAS1
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
US9758546B2 (en) 2013-10-21 2017-09-12 Ionis Pharmaceuticals, Inc. Method for solution phase detritylation of oligomeric compounds
EP3967770B1 (en) 2013-10-21 2023-12-06 The General Hospital Corporation Methods relating to circulating tumor cell clusters and the treatment of cancer
WO2015075166A1 (en) 2013-11-22 2015-05-28 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for treatment of a bacterial infection
EP3077510B1 (en) 2013-12-02 2020-05-06 Ionis Pharmaceuticals, Inc. Antisense compounds and uses thereof
WO2015089368A2 (en) 2013-12-12 2015-06-18 Alnylam Pharmaceuticals, Inc. Complement component irna compositions and methods of use thereof
EP3082840B1 (en) 2013-12-20 2021-03-24 The General Hospital Corporation Methods and assays relating to circulating tumor cells
EP3099798B1 (en) 2014-01-29 2018-06-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Oligonucleotides and methods for inhibiting or reducing bacterial biofilms
JP6594902B2 (ja) 2014-02-11 2019-10-23 アルナイラム ファーマシューティカルズ， インコーポレイテッド ケトヘキソキナーゼ（ＫＨＫ）ｉＲＮＡ組成物及びその使用方法
TWI638047B (zh) 2014-04-09 2018-10-11 史基普研究協會 藉由核酸三磷酸酯轉運子將非天然或經修飾的核苷三磷酸酯輸入至細胞中
WO2015168172A1 (en) 2014-04-28 2015-11-05 Isis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
EP4223315A3 (en) 2014-05-01 2023-08-23 Ionis Pharmaceuticals, Inc. Method for synthesis of reactive conjugate clusters
WO2015175510A1 (en) 2014-05-12 2015-11-19 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a serpinc1-associated disorder
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
MX2016015126A (es) 2014-05-22 2017-02-23 Alnylam Pharmaceuticals Inc Composiciones de angiotensinogeno (agt) arni y metodos de uso de las mismas.
JP2017518307A (ja) 2014-06-02 2017-07-06 チルドレンズ メディカル センター コーポレーション 免疫調節のための方法および組成物
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
TW201620526A (zh) 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
WO2015200697A1 (en) 2014-06-25 2015-12-30 The General Hospital Corporation Targeting human satellite ii (hsatii)
CA2955250A1 (en) 2014-07-16 2016-01-21 Moderna Therapeutics, Inc. Chimeric polynucleotides
US20170210788A1 (en) 2014-07-23 2017-07-27 Modernatx, Inc. Modified polynucleotides for the production of intrabodies
CA2959386C (en) 2014-08-29 2024-06-04 Lee Adam Wheeler Methods and compositions for the treatment of cancer
WO2016040589A1 (en) 2014-09-12 2016-03-17 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting complement component c5 and methods of use thereof
WO2016040748A1 (en) 2014-09-12 2016-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for detection of smn protein in a subject and treatment of a subject
KR20170058979A (ko) 2014-09-18 2017-05-29 더 유니버시티 오브 브리티쉬 콜롬비아 헌팅턴병 일배체형에 대한 대립 유전자-특이적 치료
JP6867945B2 (ja) 2014-10-03 2021-05-12 コールド スプリング ハーバー ラボラトリー 核内遺伝子出力の標的とされた増強
JOP20200115A1 (ar) 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات))
WO2016061487A1 (en) 2014-10-17 2016-04-21 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
WO2016069694A2 (en) 2014-10-30 2016-05-06 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof
JOP20200092A1 (ar) 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
US10364433B2 (en) 2014-11-14 2019-07-30 The Regents Of The University Of California Modulation of AGPAT5 expression
EP3221451A1 (en) 2014-11-17 2017-09-27 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
US9517270B2 (en) 2014-12-08 2016-12-13 The Board Of Regents Of The University Of Texas System Lipocationic polymers and uses thereof
US10793855B2 (en) 2015-01-06 2020-10-06 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
SG10201906716QA (en) 2015-01-20 2019-08-27 Miragen Therapeutics Inc Mir-92 inhibitors and uses thereof
JP2018503685A (ja) 2015-01-20 2018-02-08 ザ・チルドレンズ・メディカル・センター・コーポレーション 線維化を処置および予防するためのならびに創傷治癒を促進するための抗ｎｅｔ化合物
US10676726B2 (en) 2015-02-09 2020-06-09 Duke University Compositions and methods for epigenome editing
EP3256587A2 (en) 2015-02-13 2017-12-20 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
US10961532B2 (en) 2015-04-07 2021-03-30 The General Hospital Corporation Methods for reactivating genes on the inactive X chromosome
US10745702B2 (en) 2015-04-08 2020-08-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the LECT2 gene
US10407678B2 (en) 2015-04-16 2019-09-10 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
CA2983819A1 (en) 2015-04-24 2016-10-27 Atila Biosystems Incorporated Amplification with primers of limited nucleotide composition
EP3307316A1 (en) 2015-06-12 2018-04-18 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
WO2016205323A1 (en) 2015-06-18 2016-12-22 Alnylam Pharmaceuticals, Inc. Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
US20180161429A1 (en) 2015-06-26 2018-06-14 Beth Israel Deaconess Medical Center Inc. Cancer therapy targeting tetraspanin 33 (tspan33) in myeloid derived suppressor cells
WO2017004261A1 (en) 2015-06-29 2017-01-05 Ionis Pharmaceuticals, Inc. Modified crispr rna and modified single crispr rna and uses thereof
WO2017011286A1 (en) 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
AU2016294347B2 (en) 2015-07-10 2022-07-28 Ionis Pharmaceuticals, Inc. Modulators of diacyglycerol acyltransferase 2 (DGAT2)
JP7028764B2 (ja) 2015-09-02 2022-03-02 アルナイラム ファーマシューティカルズ， インコーポレイテッド プログラム細胞死１リガンド１（ＰＤ－Ｌ１）ｉＲＮＡ組成物およびその使用方法
KR20240027890A (ko) 2015-09-14 2024-03-04 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 지질양이온성 덴드리머 및 이의 용도
EP3353328A4 (en) 2015-09-24 2019-06-12 Ionis Pharmaceuticals, Inc. MODULATORS OF KRAS EXPRESSION
JP6853539B2 (ja) 2015-09-24 2021-03-31 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアＴｈｅ Ｒｅｇｅｎｔｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃａｌｉｆｏｒｎｉａ 合成スフィンゴ脂質様分子、薬物、これらの合成方法、および処置方法
WO2017060731A1 (en) 2015-10-09 2017-04-13 University Of Southampton Modulation of gene expression and screening for deregulated protein expression
US11970710B2 (en) 2015-10-13 2024-04-30 Duke University Genome engineering with Type I CRISPR systems in eukaryotic cells
US20190046555A1 (en) 2015-11-06 2019-02-14 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
WO2017096395A1 (en) 2015-12-04 2017-06-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
EP3933041B1 (en) 2015-12-14 2024-01-31 Cold Spring Harbor Laboratory Antisense oligomers for treatment of autosomal dominant retardation
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
US11761007B2 (en) 2015-12-18 2023-09-19 The Scripps Research Institute Production of unnatural nucleotides using a CRISPR/Cas9 system
WO2017120365A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
EP3418289A4 (en) 2016-02-17 2019-10-30 Tokyo Institute of Technology ARTIFICIAL NUCLEOSIDE AND ARTIFICIAL NUCLEOTIDE AND ARTIFICIAL OLIGONUCLEOTIDE
WO2017147087A1 (en) 2016-02-25 2017-08-31 The Brigham And Women's Hospital, Inc. Treatment methods for fibrosis targeting smoc2
EP3426349A4 (en) 2016-03-09 2020-01-01 Ionis Pharmaceuticals, Inc. METHODS AND COMPOSITIONS FOR INHIBITING PMP22 EXPRESSION
US10577607B2 (en) 2016-03-16 2020-03-03 Ionis Pharmaceuticals, Inc. Modulation of DYRK1B expression
AU2017234678A1 (en) 2016-03-16 2018-08-16 Ionis Pharmaceuticals, Inc. Methods of modulating KEAP1
US20190142856A1 (en) 2016-04-13 2019-05-16 Ionis Pharmaceuticals, Inc. Methods for reducing c9orf72 expression
MA45295A (fr) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser
AU2017260003B2 (en) 2016-05-06 2019-12-05 Astrazeneca Ab GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof
US10562849B2 (en) 2016-05-16 2020-02-18 The Board Of Regents Of The University Of Texas System Cationic sulfonamide amino lipids and amphiphilic zwitterionic amino lipids
WO2017214518A1 (en) 2016-06-10 2017-12-14 Alnylam Pharmaceuticals, Inc. COMPLETMENT COMPONENT C5 iRNA COMPOSTIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
AU2017286811A1 (en) 2016-06-17 2018-11-22 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
ES2929047T3 (es) 2016-06-24 2022-11-24 Scripps Research Inst Transportador de nucleósido trifosfato novedoso y usos del mismo
KR102556825B1 (ko) 2016-07-15 2023-07-17 아이오니스 파마수티컬즈, 인코포레이티드 Smn2 조정을 위한 조성물 및 방법
CA3037042A1 (en) 2016-09-14 2018-03-22 Janssen Biopharma, Inc. Modified oligonucleotides and methods of use
KR102468174B1 (ko) 2016-09-15 2022-11-17 에프. 호프만-라 로슈 아게 멀티플렉스 pcr 수행 방법
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
EP3532638A4 (en) 2016-10-31 2020-07-29 University of Massachusetts TARGETING MICROARN-101-3 P IN CARCINOTHERAPY
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
US11033570B2 (en) 2016-12-02 2021-06-15 Cold Spring Harbor Laboratory Modulation of Lnc05 expression
WO2018112320A1 (en) 2016-12-16 2018-06-21 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
JOP20180003B1 (ar) 2017-01-10 2022-09-15 Arrowhead Pharmaceuticals Inc عوامل RNAi ألفا-1 مضادة للتريبسين (AAT)، وتركيبات تتضمن عوامل AAT RNAi، وطرق الاستخدام
US11180756B2 (en) 2017-03-09 2021-11-23 Ionis Pharmaceuticals Morpholino modified oligomeric compounds
WO2018169063A1 (ja) 2017-03-17 2018-09-20 国立大学法人千葉大学 構造強化されたＳ－ＴｕＤを用いた新規がん治療法
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
KR20200015895A (ko) 2017-04-18 2020-02-13 알닐람 파마슈티칼스 인코포레이티드 B형 간염 바이러스 (hbv)에 감염된 대상체의 치료 방법
SG11202000167SA (en) 2017-07-11 2020-02-27 Synthorx Inc Incorporation of unnatural nucleotides and methods thereof
MA49770A (fr) 2017-08-03 2021-05-26 Synthorx Inc Conjugués de cytokine destinés au traitement de maladies prolifératives et infectieuses
EP3668984A4 (en) 2017-08-18 2021-09-08 Ionis Pharmaceuticals, Inc. MODULATION OF THE NOTCH SIGNALING PATH FOR THE TREATMENT OF RESPIRATORY DISORDERS
PL3673080T3 (pl) 2017-08-25 2024-03-11 Stoke Therapeutics, Inc. Oligomery antysensowne do leczenia stanów i chorób
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. MODULATORS OF SMAD7 EXPRESSION
AU2018332216B2 (en) 2017-09-14 2024-05-02 Janssen Biopharma, Inc. Galnac derivatives
US11261445B2 (en) 2017-10-17 2022-03-01 Inserm (Institut National De La Sante Et De La Recherche Medicale) Combination treatment for cystic fibrosis
AU2018360697A1 (en) 2017-11-01 2020-05-14 Alnylam Pharmaceuticals, Inc. Complement component C3 iRNA compositions and methods of use thereof
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
US20200385719A1 (en) 2017-11-16 2020-12-10 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
EP3714054A1 (en) 2017-11-20 2020-09-30 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
US11725208B2 (en) 2017-12-14 2023-08-15 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
BR112020012088A2 (pt) 2017-12-18 2020-11-17 Alnylam Pharmaceuticals, Inc. composições de irna do grupo de elevada mobilidade box-1 (hmgb1) e métodos de uso dos mesmos
EP3740575A1 (en) 2018-01-15 2020-11-25 Ionis Pharmaceuticals, Inc. Modulators of dnm2 expression
EP3752612A4 (en) 2018-02-12 2021-11-10 Ionis Pharmaceuticals, Inc. MODIFIED COMPOUNDS AND USES THEREOF
AU2019224159A1 (en) 2018-02-26 2020-10-01 Synthorx, Inc. IL-15 conjugates and uses thereof
BR112020018365A2 (pt) 2018-03-13 2020-12-29 Janssen Pharmaceutica Nv Oligonucleotídeos modificados e métodos para uso em tauopatias
EP3799604A4 (en) 2018-05-09 2022-09-07 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING FXI EXPRESSION
TW202016304A (zh) 2018-05-14 2020-05-01 美商阿尼拉製藥公司 血管收縮素原（ＡＧＴ）ｉＲＮＡ組成物及其使用方法
WO2019226952A1 (en) 2018-05-24 2019-11-28 Valkyrie Pharmaceutics, Inc. Methods and formulations for the treatment of obesity and obesity-related metabolic diseases
AU2019310097A1 (en) 2018-07-25 2021-02-04 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ATXN2 expression
US20210308170A1 (en) 2018-07-27 2021-10-07 Osaka University Composition for suppression of aging, prevention, amelioration, or treatment of an age-related disease or symptom, or extension of lifespan
EP3833762A4 (en) 2018-08-09 2022-09-28 Verseau Therapeutics, Inc. OLIGONUCLEOTIDE COMPOSITIONS FOR TARGETING CCR2 AND CSF1R AND THEIR USES
MX2021001056A (es) 2018-08-13 2021-04-12 Alnylam Pharmaceuticals Inc Composiciones de agente de acido ribonucleico bicatenario (arnbc) de virus de la hepatitis b (vhb) y metodos de uso de las mismas.
TW202020157A (zh) 2018-08-16 2020-06-01 美商艾爾妮蘭製藥公司 用於抑制lect2基因表現之組合物及方法
BR112021003224A2 (pt) 2018-08-20 2021-07-20 Rogcon, Inc. oligonucleotídeos antissentido direcionados a scn2a para o tratamento de encefalopatias por scn1a
CA3110661A1 (en) 2018-08-29 2020-03-05 University Of Massachusetts Inhibition of protein kinases to treat friedreich ataxia
EP3620520A1 (en) 2018-09-10 2020-03-11 Universidad del Pais Vasco Novel target to treat a metabolic disease in an individual
JP2022500003A (ja) 2018-09-18 2022-01-04 アルナイラム ファーマシューティカルズ, インコーポレイテッドAlnylam Pharmaceuticals, Inc. ケトヘキソキナーゼ（ＫＨＫ）ｉＲＮＡ組成物およびその使用方法
TW202023573A (zh) 2018-09-19 2020-07-01 美商Ionis製藥公司 Pnpla3表現之調節劑
US10913951B2 (en) 2018-10-31 2021-02-09 University of Pittsburgh—of the Commonwealth System of Higher Education Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
EP3880821A4 (en) 2018-11-15 2023-01-25 Ionis Pharmaceuticals, Inc. IRF5 EXPRESSION MODULATORS
CN113286886A (zh) 2018-11-21 2021-08-20 Ionis制药公司 用于减少朊病毒表达的化合物和方法
SG11202012758WA (en) 2018-12-17 2021-01-28 Illumina Cambridge Ltd Primer oligonucleotide for sequencing
CN113195734A (zh) 2018-12-20 2021-07-30 豪夫迈·罗氏有限公司 通过固相分子成像检测靶核酸
LT3897672T (lt) 2018-12-20 2023-11-10 Vir Biotechnology, Inc. Kombinuota hbv terapija
WO2020132521A1 (en) 2018-12-20 2020-06-25 Praxis Precision Medicines, Inc. Compositions and methods for the treatment of kcnt1 related disorders
MX2021008628A (es) 2019-01-16 2021-11-17 Genzyme Corp Composiciones de arni para serpinc1 y metodos de uso de las mismas.
CA3128093A1 (en) 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulators of yap1 expression
EP3923974A4 (en) 2019-02-06 2023-02-08 Synthorx, Inc. IL-2 CONJUGATES AND METHODS OF USE THEREOF
JPWO2020184700A1 (ja) 2019-03-14 2020-09-17
WO2020191177A1 (en) 2019-03-21 2020-09-24 Sudhir Agrawal Antisense oligonucleotides for allele specificity
JP2022530678A (ja) 2019-05-03 2022-06-30 ディセルナ ファーマシューティカルズ インコーポレイテッド 短縮センス鎖を有する二本鎖核酸阻害剤分子
BR112021022806A2 (pt) 2019-05-13 2022-01-25 Vir Biotechnology Inc Método para tratar a infecção crônica por hbv, sirna, usos de um sirna, e de um sirna e peg-ifna e de um sirna, peg-ifna e um nrti, método, composição para uso ou uso e kit
TW202111123A (zh) 2019-05-28 2021-03-16 美商Ionis製藥公司 用於減少fus 表現之化合物及方法
CN114207129A (zh) 2019-06-14 2022-03-18 斯克利普斯研究所 用于在半合成生物体中复制、转录和翻译的试剂和方法
WO2020256084A1 (ja) 2019-06-19 2020-12-24 ヤマサ醤油株式会社 架橋型ヌクレオシド中間体の結晶及びその製造方法、並びに架橋型ヌクレオシドアミダイトの製造方法
US20220251567A1 (en) 2019-07-10 2022-08-11 Inserm (Institut National De La Santè Et De La Recherche Médicale) Methods for the treatment of epilepsy
EP3956450A4 (en) 2019-07-26 2022-11-16 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATION OF GFAP
EP4007811A2 (en) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Carboxypeptidase b2 (cpb2) irna compositions and methods of use thereof
WO2021022109A1 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4013870A1 (en) 2019-08-13 2022-06-22 Alnylam Pharmaceuticals, Inc. Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof
WO2021030778A1 (en) 2019-08-15 2021-02-18 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
KR20220047598A (ko) 2019-08-15 2022-04-18 신톡스, 인크. Il-2 콘쥬게이트를 사용한 면역 종양학 병용 요법
JP2022544817A (ja) 2019-08-23 2022-10-21 シンソークス， インコーポレイテッド Ｉｌ－１５コンジュゲートおよびその使用
EP4025694A1 (en) 2019-09-03 2022-07-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
WO2021050554A1 (en) 2019-09-10 2021-03-18 Synthorx, Inc. Il-2 conjugates and methods of use to treat autoimmune diseases
EP4038189A1 (en) 2019-10-04 2022-08-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing ugt1a1 gene expression
CN114728017A (zh) 2019-10-14 2022-07-08 阿斯利康(瑞典)有限公司 Pnpla3表达的调节剂
WO2021074657A1 (en) 2019-10-17 2021-04-22 INSERM (Institut National de la Santé et de la Recherche Médicale) Combination treatment for cystic fibrosis
EP4045652A1 (en) 2019-10-18 2022-08-24 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
WO2021081026A1 (en) 2019-10-22 2021-04-29 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
EP4051796A1 (en) 2019-11-01 2022-09-07 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajb1-prkaca fusion gene expression
AU2020376840A1 (en) 2019-11-01 2022-04-07 Alnylam Pharmaceuticals, Inc. Huntingtin (HTT) iRNA agent compositions and methods of use thereof
TW202131952A (zh) 2019-11-04 2021-09-01 美商欣爍克斯公司 介白素10接合物及其用途
KR20220115946A (ko) 2019-11-13 2022-08-19 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물
WO2021099394A1 (en) 2019-11-19 2021-05-27 INSERM (Institut National de la Santé et de la Recherche Médicale) Antisense oligonucleotides and their use for the treatment of cancer
US20230056569A1 (en) 2019-11-22 2023-02-23 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
EP3831843A1 (en) 2019-12-08 2021-06-09 Royal College Of Surgeons In Ireland A hemostatic agent and uses thereof
MX2022006433A (es) 2019-12-13 2022-06-23 Alnylam Pharmaceuticals Inc Composiciones de agentes de acido ribonucleico de interferencia (arni) del marco de lectura abierto 72 del cromosoma 9 humano (c9orf72) y metodos de uso de los mismos.
WO2021126734A1 (en) 2019-12-16 2021-06-24 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
WO2021153747A1 (ja) 2020-01-31 2021-08-05 株式会社三和化学研究所 Ａｔｎ１のアンチセンスオリゴヌクレオチド
WO2021154941A1 (en) 2020-01-31 2021-08-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als)
IL295445A (en) 2020-02-10 2022-10-01 Alnylam Pharmaceuticals Inc Preparations and methods for silencing vegf-a expression
IL295496A (en) 2020-02-18 2022-10-01 Alnylam Pharmaceuticals Inc Apolipoprotein c3 (apoc3) irna preparations and methods of using them
CA3173034A1 (en) 2020-02-28 2021-09-02 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating smn2
JPWO2021177418A1 (ja) 2020-03-04 2021-09-10
WO2021178607A1 (en) 2020-03-05 2021-09-10 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
CN115461460A (zh) 2020-03-06 2022-12-09 阿尔尼拉姆医药品有限公司 用于抑制转甲状腺素蛋白(ttr)的表达的组合物和方法
CN115485383A (zh) 2020-03-06 2022-12-16 阿尔尼拉姆医药品有限公司 己酮糖激酶(KHK)iRNA组合物及其使用方法
WO2021188611A1 (en) 2020-03-18 2021-09-23 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
WO2021195307A1 (en) 2020-03-26 2021-09-30 Alnylam Pharmaceuticals, Inc. Coronavirus irna compositions and methods of use thereof
EP4127171A2 (en) 2020-03-30 2023-02-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajc15 gene expression
BR112022020145A2 (pt) 2020-04-06 2023-01-03 Alnylam Pharmaceuticals Inc Composições e métodos para silenciamento da expressão de myoc
EP4133076A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof
EP4133079A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing scn9a expression
WO2021206922A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
AU2021263554A1 (en) 2020-04-27 2022-12-08 Alnylam Pharmaceuticals, Inc. Apolipoprotein E (APOE) iRNA agent compositions and methods of use thereof
BR112022021136A2 (pt) 2020-04-30 2022-11-29 Alnylam Pharmaceuticals Inc Composições de irna de fator b de complemento (cfb) e métodos de uso das mesmas
KR20230022409A (ko) 2020-05-11 2023-02-15 스톡 테라퓨틱스, 인크. 병태 및 질환의 치료를 위한 opa1 안티센스 올리고머
EP4150077A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
WO2021231692A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
WO2021231675A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
WO2021231679A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
WO2021231698A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
WO2021231673A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2)
EP4150089A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rs1)
EP4150076A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
EP4153746A1 (en) 2020-05-21 2023-03-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting marc1 gene expression
AR122534A1 (es) 2020-06-03 2022-09-21 Triplet Therapeutics Inc Métodos para el tratamiento de los trastornos de expansión por repetición de nucleótidos asociados con la actividad de msh3
EP4162050A1 (en) 2020-06-09 2023-04-12 Alnylam Pharmaceuticals, Inc. Rnai compositions and methods of use thereof for delivery by inhalation
EP4168546A1 (en) 2020-06-18 2023-04-26 Alnylam Pharmaceuticals, Inc. Xanthine dehydrogenase (xdh) irna compositions and methods of use thereof
BR112022026316A2 (pt) 2020-06-24 2023-03-07 Vir Biotechnology Inc Anticorpos neutralizantes do vírus da hepatite b engenheirados e usos dos mesmos
WO2021263026A1 (en) 2020-06-25 2021-12-30 Synthorx, Inc. Immuno oncology combination therapy with il-2 conjugates and anti-egfr antibodies
WO2022011262A1 (en) 2020-07-10 2022-01-13 Inserm (Institut National De La Sante Et De La Recherche Medicale) Methods and compositions for treating epilepsy
TW202227102A (zh) 2020-09-22 2022-07-16 瑞典商阿斯特捷利康公司 治療脂肪肝病之方法
WO2022066847A1 (en) 2020-09-24 2022-03-31 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
EP4225917A1 (en) 2020-10-05 2023-08-16 Alnylam Pharmaceuticals, Inc. G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof
EP4225375A1 (en) 2020-10-09 2023-08-16 Synthorx, Inc. Immuno oncology therapies with il-2 conjugates
MX2023004029A (es) 2020-10-09 2023-04-27 Synthorx Inc Terapia de combinacion de inmunoncologia con conjugados de il-2 y pembrolizumab.
AU2021365822A1 (en) 2020-10-21 2023-06-08 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating primary hyperoxaluria
WO2022087329A1 (en) 2020-10-23 2022-04-28 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
IL302709A (en) 2020-11-13 2023-07-01 Alnylam Pharmaceuticals Inc Coagulation factor iRNA compositions (F5) and methods of using them
EP4247949A1 (en) 2020-11-23 2023-09-27 Alpha Anomeric SAS Nucleic acid duplexes
TW202237150A (zh) 2020-12-01 2022-10-01 美商艾拉倫製藥股份有限公司 用於抑制ｈａｏ１（羥基酸氧化酶１（乙醇酸氧化酶））基因表現的方法及組成物
EP4259795A1 (en) 2020-12-08 2023-10-18 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
EP4265627A1 (en) 2020-12-11 2023-10-25 Yamasa Corporation Cytosine-type crosslinked nucleoside amidite crystals and method for producing same
MX2023007257A (es) 2020-12-18 2023-07-03 Ionis Pharmaceuticals Inc Compuestos y metodos para modular el factor xii.
US20240035077A1 (en) 2020-12-22 2024-02-01 Roche Molecular Systems, Inc. Methods for performing multiplexed real-time pcr with the use of large stokes shift fluorescent dyes
WO2022150260A1 (en) 2021-01-05 2022-07-14 Alnylam Pharmaceuticals, Inc. COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2022174102A1 (en) 2021-02-12 2022-08-18 Synthorx, Inc. Lung cancer combination therapy with il-2 conjugates and an anti-pd-1 antibody or antigen-binding fragment thereof
TW202245843A (zh) 2021-02-12 2022-12-01 美商欣爍克斯公司 Ｉｌ－２接合物及西米普利單抗（ｃｅｍｉｐｌｉｍａｂ）之皮膚癌組合療法
IL304880A (en) 2021-02-12 2023-10-01 Alnylam Pharmaceuticals Inc Superoxide dismutase 1 (SOD1) IRNA compositions and methods of using them to treat or prevent superoxide dismutase 1- (SOD1-) associated neurodegenerative diseases
EP4298220A1 (en) 2021-02-25 2024-01-03 Alnylam Pharmaceuticals, Inc. Prion protein (prnp) irna compositions and methods of use thereof
IL305153A (en) 2021-02-26 2023-10-01 Alnylam Pharmaceuticals Inc Ketohexokinase (KHK) iRNA compositions and methods of using them
WO2022187435A1 (en) 2021-03-04 2022-09-09 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
WO2022192519A1 (en) 2021-03-12 2022-09-15 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
US20220290221A1 (en) 2021-03-15 2022-09-15 Roche Molecular Systems, Inc. Compositions and methods for detecting severe acute respiratory syndrome coronavirus 2 (sars-cov-2) variants having spike protein mutations
IL307239A (en) 2021-03-29 2023-11-01 Alnylam Pharmaceuticals Inc Preparations containing Huntingtin IRNA factor (HTT) and methods of using them
WO2022212153A1 (en) 2021-04-01 2022-10-06 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
JP2024517686A (ja) 2021-04-26 2024-04-23 アルナイラム ファーマシューティカルズ， インコーポレイテッド 膜貫通プロテアーゼ、セリン６（ＴＭＰＲＳＳ６）ｉＲＮＡ組成物およびその使用方法
JP2024519293A (ja) 2021-04-29 2024-05-10 アルナイラム ファーマシューティカルズ， インコーポレイテッド シグナル伝達兼転写活性化因子６（ＳＴＡＴ６）ｉＲＮＡ組成物およびその使用方法
JP2024522068A (ja) 2021-05-18 2024-06-11 アルナイラム ファーマシューティカルズ， インコーポレイテッド ナトリウム－グルコース共輸送体２（ｓｇｌｔ２）ｉｒｎａ組成物およびその使用方法
EP4341405A1 (en) 2021-05-20 2024-03-27 Korro Bio, Inc. Methods and compositions for adar-mediated editing
CA3222167A1 (en) 2021-05-31 2022-12-08 Rena Therapeutics Inc. Ligand-binding nucleic acid complex
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
EP4347823A1 (en) 2021-06-02 2024-04-10 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
EP4346904A1 (en) 2021-06-03 2024-04-10 Synthorx, Inc. Head and neck cancer combination therapy comprising an il-2 conjugate and cetuximab
BR112023025224A2 (pt) 2021-06-04 2024-02-27 Alnylam Pharmaceuticals Inc Quadro de leitura aberto 72 do cromossomo humano 9 (c9orf72) composições de agente de irna e métodos de uso dos mesmos
WO2022260939A2 (en) 2021-06-08 2022-12-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
KR20240037226A (ko) 2021-06-22 2024-03-21 아큐라스템 인코포레이티드 Pikfyve 안티센스 올리고뉴클레오티드
WO2023278410A1 (en) 2021-06-29 2023-01-05 Korro Bio, Inc. Methods and compositions for adar-mediated editing
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
KR20240026203A (ko) 2021-06-30 2024-02-27 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐(agt)-관련 장애를 치료하는 방법 및 조성물
WO2023003805A1 (en) 2021-07-19 2023-01-26 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder
EP4373935A1 (en) 2021-07-21 2024-05-29 Acurastem, Inc. Unc13a antisense oligonucleotides
AU2022316139A1 (en) 2021-07-23 2024-01-18 Alnylam Pharmaceuticals, Inc. Beta-catenin (ctnnb1) irna compositions and methods of use thereof
WO2023009687A1 (en) 2021-07-29 2023-02-02 Alnylam Pharmaceuticals, Inc. 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof
CN117795074A (zh) 2021-08-03 2024-03-29 阿尔尼拉姆医药品有限公司 转甲状腺素蛋白（TTR）iRNA组合物和其使用方法
IL310295A (en) 2021-08-04 2024-03-01 Alnylam Pharmaceuticals Inc iRNA compositions and methods for silencing angiotensinogen (AGT)
IL310407A (en) 2021-08-13 2024-03-01 Alnylam Pharmaceuticals Inc Factor XII (F12) IRNA compositions and methods of using them
US11833221B2 (en) 2021-09-01 2023-12-05 Ionis Pharmaceuticals, Inc. Oligomeric compounds for reducing DMPK expression
WO2023044370A2 (en) 2021-09-17 2023-03-23 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
AU2022345881A1 (en) 2021-09-20 2024-03-21 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
CA3234835A1 (en) 2021-10-22 2023-04-27 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
TW202334418A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 杭丁頓（ＨＴＴ）ｉＲＮＡ劑組成物及其使用方法
CA3234636A1 (en) 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. Complement factor b (cfb) irna compositions and methods of use thereof
CA3237769A1 (en) 2021-11-10 2023-05-19 University Of Rochester Gata4-targeted therapeutics for treatment of cardiac hypertrophy
WO2023086295A2 (en) 2021-11-10 2023-05-19 University Of Rochester Antisense oligonucleotides for modifying protein expression
GB202117758D0 (en) 2021-12-09 2022-01-26 Ucl Business Ltd Therapeutics for the treatment of neurodegenerative disorders
WO2023122573A1 (en) 2021-12-20 2023-06-29 Synthorx, Inc. Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab
WO2023118150A1 (en) 2021-12-22 2023-06-29 Royal College Of Surgeons In Ireland A conjugate for use in localising a molecule to the vascular endothelium.
WO2023122750A1 (en) 2021-12-23 2023-06-29 Synthorx, Inc. Cancer combination therapy with il-2 conjugates and cetuximab
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
WO2023152369A1 (en) 2022-02-14 2023-08-17 INSERM (Institut National de la Santé et de la Recherche Médicale) Nucleic acid mir-9 inhibitor for the treatment of cystic fibrosis
WO2023212625A1 (en) 2022-04-28 2023-11-02 AcuraStem Incorporated Syf2 antisense oligonucleotides
WO2024017990A1 (en) 2022-07-21 2024-01-25 Institut National de la Santé et de la Recherche Médicale Methods and compositions for treating chronic pain disorders
WO2024040041A1 (en) 2022-08-15 2024-02-22 Dicerna Pharmaceuticals, Inc. Regulation of activity of rnai molecules
WO2024050261A1 (en) 2022-08-29 2024-03-07 University Of Rochester Antisense oligonucleotide-based anti-fibrotic therapeutics
WO2024059165A1 (en) 2022-09-15 2024-03-21 Alnylam Pharmaceuticals, Inc. 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5859221A (en) * 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
JPH0953409A (ja) 1995-08-15 1997-02-25 Mitsubishi Heavy Ind Ltd ガスタービン用セラミック静翼
GB9612600D0 (en) * 1996-06-13 1996-08-21 Ciba Geigy Ag Chemical compounds
JP3756313B2 (ja) † 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
EP2341058A3 (en) † 1997-09-12 2011-11-23 Exiqon A/S Oligonucleotide Analogues

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ALTMANN K.-H., KESSELRING R., PIELES U.: "6'-CARBON-SUBSTITUTED CARBOCYCLIC ANALOGS OF 2'-DEOXYRIBONUCLEOSIDES - SYNTHESIS AND EFFECT ON DNA/RNA DUPLEX STABILITY.", TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 52., no. 39., 1 January 1996 (1996-01-01), AMSTERDAM, NL, pages 12699 - 12722., XP002916465, ISSN: 0040-4020, DOI: 10.1016/0040-4020(96)00755-7 *
OBIKA ET AL.: "Properties of Novel oligonucleotide Analogues Containing an Acyclic Nucleoside and a Carbamate Linkage", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 6, no. 12, 1996, pages 1357 - 1360
OBIKA S., ET AL.: "PROPERTIES OF NOVEL OLIGONUCLEOTIDE ANALOGUES CONTAINING AN ACYCLIC NUCLEOSIDE AND A CARBAMATE LINKAGE.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, AMSTERDAM, NL, vol. 06., no. 12., 1 January 1996 (1996-01-01), AMSTERDAM, NL, pages 1357 - 1360., XP002916466, ISSN: 0960-894X, DOI: 10.1016/0960-894X(96)00223-5 *
OBIKA S., ET AL.: "SYNTHESIS OF 2'-O,4'-C-METHYLENEURIDINE AND -CYTIDINE. NOVEL BICYCLIC NUCLEOSIDES HAVING A FIXED C3,-ENDO SUGAR PUCKERING.", TETRAHEDRON LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 38., no. 50., 15 December 1997 (1997-12-15), AMSTERDAM, NL, pages 8735 - 8738., XP002916464, ISSN: 0040-4039, DOI: 10.1016/S0040-4039(97)10322-7 *

Cited By (877)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
US7695902B2 (en) 1996-06-06 2010-04-13 Isis Pharmaceuticals, Inc. Oligoribonucleotides and ribonucleases for cleaving RNA
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US8153365B2 (en) 1997-09-12 2012-04-10 Exiqon A/S Oligonucleotide analogues
US8034909B2 (en) 1997-09-12 2011-10-11 Exiqon A/S Oligonucleotide analogues
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US8080644B2 (en) 1997-09-12 2011-12-20 Exiqon A/S Oligonucleotide analogues
US7034133B2 (en) 1997-09-12 2006-04-25 Exiqon A/S Oligonucleotide analogues
US6670461B1 (en) 1997-09-12 2003-12-30 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7816333B2 (en) 1999-02-12 2010-10-19 Daiichi Sankyo Company, Limited Oligonucleotide analogues and methods utilizing the same
US8957201B2 (en) 1999-02-12 2015-02-17 Daiichi Sankyo Company, Limited Oligonucleotide analogues and methods utilizing the same
US7335765B2 (en) 1999-02-12 2008-02-26 Daiichi Sankyo Company, Limited Nucleoside and oligonucleotide analogues
AU758956B2 (en) * 1999-02-12 2003-04-03 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
US7314923B2 (en) 1999-02-12 2008-01-01 Daiichi Sankyo Company, Limited Nucleoside and oligonucleotide analogues
WO2000047599A1 (fr) * 1999-02-12 2000-08-17 Sankyo Company, Limited Nouveaux analogues de nucleosides et d'oligonucleotides
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US6303315B1 (en) 1999-03-18 2001-10-16 Exiqon A/S One step sample preparation and detection of nucleic acids in complex biological samples
WO2000056748A1 (en) * 1999-03-18 2000-09-28 Exiqon A/S Xylo-lna analogues
US6316198B1 (en) 1999-03-18 2001-11-13 Exiqon A/S Detection of mutations in genes by specific LNA primers
AU777049B2 (en) * 1999-03-18 2004-09-30 Qiagen Gmbh Xylo-LNA analogues
US6639059B1 (en) 1999-03-24 2003-10-28 Exiqon A/S Synthesis of [2.2.1]bicyclo nucleosides
US6734291B2 (en) 1999-03-24 2004-05-11 Exiqon A/S Synthesis of [2.2.1]bicyclo nucleosides
WO2000066604A3 (en) * 1999-05-04 2001-01-11 Exiqon As L-ribo-lna analogues
WO2000066604A2 (en) * 1999-05-04 2000-11-09 Exiqon A/S L-ribo-lna analogues
US7053207B2 (en) 1999-05-04 2006-05-30 Exiqon A/S L-ribo-LNA analogues
WO2001007455A1 (fr) * 1999-07-22 2001-02-01 Sankyo Company, Limited Analogues de bicyclonucléosides
US7994145B2 (en) 1999-07-22 2011-08-09 Takeshi Imanishi Bicyclonucleoside analogues
US7217805B2 (en) 1999-07-22 2007-05-15 Sankyo Company, Limited Bicyclonucleoside analogues
AU766656B2 (en) * 1999-07-22 2003-10-23 Takeshi Imanishi Novel bicyclonucleoside analogues
WO2001048190A2 (en) * 1999-12-23 2001-07-05 Exiqon A/S Therapeutic uses of lna-modified oligonucleotides
WO2001048190A3 (en) * 1999-12-23 2002-05-10 Exiqon As Therapeutic uses of lna-modified oligonucleotides
EP2316975A1 (en) 2000-06-06 2011-05-04 Applied Biosystems, LLC Asynchronous primed PCR
EP2256213A1 (en) 2000-06-06 2010-12-01 Applied Biosystems, LLC Asynchronous primed PCR
WO2002018388A1 (fr) * 2000-08-29 2002-03-07 Takeshi Imanishi Analogues de nucleosides et derives d'oligonucleotides renfermant ces analogues
EP2179996A1 (en) 2000-11-28 2010-04-28 Applera Corporation Sulfonated diarylrhodamine dyes
EP2221347A1 (en) 2000-11-28 2010-08-25 Applera Corporation Sulfonated diarylrhodamine dyes
US7229767B2 (en) 2001-03-27 2007-06-12 University Of Delaware Genomics applications for modified OLIGO nucleotides
EP1992643A2 (en) 2001-06-20 2008-11-19 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2000545A1 (en) 2001-06-20 2008-12-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2000148A1 (en) 2001-06-20 2008-12-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of prostate cancer
EP2000482A1 (en) 2001-06-20 2008-12-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2221376A2 (en) 2001-06-21 2010-08-25 Isis Pharmaceuticals, Inc. Antisense modulation of superoxide dismutase 1, soluble expression
EP2270024A1 (en) 2001-06-21 2011-01-05 ISIS Pharmaceuticals, Inc. Antisense modulation of superoxide dismutase 1, soluble expression
US6822088B2 (en) 2001-07-17 2004-11-23 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides on solid support
US7829275B2 (en) 2001-07-20 2010-11-09 North Carolina State University Light addressable electrochemical detection of duplex structures
EP2280019A1 (en) 2001-07-25 2011-02-02 ISIS Pharmaceuticals, Inc. Antisense modulation of C-reactive protein expression
EP2332955A2 (en) 2001-07-30 2011-06-15 ISIS Pharmaceuticals, Inc. Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression
EP2174945A1 (en) 2001-08-01 2010-04-14 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2336145A1 (en) 2001-08-01 2011-06-22 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2272985A1 (en) 2001-08-07 2011-01-12 ISIS Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (A) expression
EP2316968A1 (en) 2001-08-07 2011-05-04 ISIS Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (A) expression
EP2151244A1 (en) 2001-09-18 2010-02-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2153843A1 (en) 2001-09-18 2010-02-17 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2143437A1 (en) 2001-09-18 2010-01-13 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2143438A1 (en) 2001-09-18 2010-01-13 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP2270231A2 (en) 2001-10-09 2011-01-05 ISIS Pharmaceuticals, Inc. Antisense modulation of insulin-like growth factor binding protein 5 expression
EP2270230A2 (en) 2001-10-09 2011-01-05 ISIS Pharmaceuticals, Inc. Antisense modulation of insulin-like growth factor binding protein 5 expression
WO2003033696A1 (fr) * 2001-10-18 2003-04-24 Sankyo Company, Limited Compose antisens vegf
EP2196544A1 (en) 2001-11-21 2010-06-16 Applied Biosystems, LLC Kit for ligation detection assays using codeable labels
EP2388318A1 (en) 2001-12-10 2011-11-23 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
EP2067472A1 (en) 2002-01-02 2009-06-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7566535B2 (en) 2002-03-07 2009-07-28 University Of Delaware Enhanced oligonucleotide-mediated nucleic acid sequence alteration
EP2011886A2 (en) 2002-04-16 2009-01-07 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
US8492390B2 (en) 2002-05-08 2013-07-23 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
US7005265B1 (en) 2002-06-20 2006-02-28 Wenhong Fan Nonenzymatic catalytic signal amplification for nucleic acid hybridization assays
EP2330194A2 (en) 2002-09-13 2011-06-08 Replicor, Inc. Non-sequence complementary antiviral oligonucleotides
US8008270B2 (en) 2002-09-13 2011-08-30 Replicor Inc. Antiviral oligonucleotides targeting viral families
US8067385B2 (en) 2002-09-13 2011-11-29 Replicor, Inc. Antiviral oligonucleotides targeting HBV
US8008269B2 (en) 2002-09-13 2011-08-30 Replicor Inc. Antiviral oligonucleotides
US7358068B2 (en) 2002-09-13 2008-04-15 Replicor, Inc. Antiviral oligonucleotides
EP2272958A1 (en) 2002-09-26 2011-01-12 ISIS Pharmaceuticals, Inc. Modulation of forkhead box O1A expression
US9464106B2 (en) 2002-10-21 2016-10-11 Exiqon A/S Oligonucleotides useful for detecting and analyzing nucleic acids of interest
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
US7696345B2 (en) 2002-11-05 2010-04-13 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP2336318A1 (en) 2002-11-13 2011-06-22 Genzyme Corporation Antisense modulation of apolipoprotein B expression
EP2336319A1 (en) 2002-11-13 2011-06-22 Genzyme Corporation Antisense modulation of apolipoprotein B expression
US9994850B2 (en) 2002-11-18 2018-06-12 Roche Innovation Center Copenhagen A/S Antisense design
US9428534B2 (en) 2002-11-18 2016-08-30 Roche Innovation Center Copenhagen A/S Antisense design
EP2752488A2 (en) 2002-11-18 2014-07-09 Santaris Pharma A/S Antisense design
US9708614B2 (en) 2002-11-18 2017-07-18 Roche Innovation Center Copenhagen A/S Antisense design
US9045518B2 (en) 2002-11-18 2015-06-02 Santaris Pharma A/S Amino-LNA, thio-LNA and alpha-L-oxy-LN
US7687617B2 (en) 2002-11-18 2010-03-30 Santaris Pharma A/S Oligonucleotides with alternating segments of locked and non-locked nucleotides
EP3222722A1 (en) 2002-11-18 2017-09-27 Roche Innovation Center Copenhagen A/S Antisense design
US9890383B2 (en) 2002-11-18 2018-02-13 Roche Innovation Center Copenhagen A/S Antisense design
US9951333B2 (en) 2002-11-18 2018-04-24 Roche Innovation Center Copenhagen A/S Antisense design
EP2284269A2 (en) 2002-11-18 2011-02-16 Santaris Pharma A/S Antisense design
EP2363503A1 (en) 2002-11-23 2011-09-07 ISIS Pharmaceuticals, Inc. Modulation of HIF1A and HIF2A expression
WO2004072284A1 (en) 2003-02-11 2004-08-26 Antisense Therapeutics Ltd Modulation of insulin like growth factor i receptor expression
WO2004078922A2 (en) 2003-02-28 2004-09-16 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
EP2492282A1 (en) 2003-02-28 2012-08-29 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
EP2281869A2 (en) 2003-03-21 2011-02-09 ISIS Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 1 expression
WO2004096124A2 (en) 2003-04-01 2004-11-11 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP3002007A1 (en) 2003-04-16 2016-04-06 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein c-iii expression
EP3412284A1 (en) 2003-04-16 2018-12-12 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein c-iii expression
EP2441449A1 (en) 2003-04-16 2012-04-18 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein C-III expression
EP2272857A1 (en) 2003-04-28 2011-01-12 ISIS Pharmaceuticals, Inc. Modulation of glucagon receptor expression
EP2327709A2 (en) 2003-04-28 2011-06-01 ISIS Pharmaceuticals, Inc. Modulation of glucagon receptor expression
EP2266997A1 (en) 2003-06-02 2010-12-29 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
EP2218727A1 (en) 2003-06-02 2010-08-18 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
EP2241572A2 (en) 2003-06-03 2010-10-20 Eli Lilly And Company Modulation of survivin expression
US11111535B2 (en) 2003-06-20 2021-09-07 Qiagen Gmbh Probes, libraries and kits for analysis of mixtures of nucleic acids and methods for constructing the same
EP2530157A2 (en) 2003-07-31 2012-12-05 Regulus Therapeutics, Inc Oligomeric compounds and compositions for use in modulation of small non-coding rnas
EP2284267A2 (en) 2003-08-18 2011-02-16 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
WO2005019418A2 (en) 2003-08-18 2005-03-03 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 2 expression
EP2256200A2 (en) 2003-09-18 2010-12-01 ISIS Pharmaceuticals, Inc. Modulation of eIF4E expression
EP2256201A2 (en) 2003-09-18 2010-12-01 ISIS Pharmaceuticals, Inc. Modulation of eIF4E expression
EP2444482A1 (en) 2003-11-03 2012-04-25 Isis Pharmaceuticals, Inc. Modulation of SGLT2 expression
WO2005049630A2 (en) 2003-11-17 2005-06-02 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
EP2295073A1 (en) 2003-11-17 2011-03-16 Genentech, Inc. Antibody against CD22 for the treatment of tumour of hematopoietic origin
EP2301568A1 (en) 2003-11-17 2011-03-30 Genentech, Inc. Antibody against IRTA2 for the treatment of tumour of hematopoietic origin
EP2253706A2 (en) 2003-11-17 2010-11-24 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
EP2161283A1 (en) 2003-11-17 2010-03-10 Genentech, Inc. Compositions comprising antibodies against CD79b conjugated to a growth inhibitory agent or cytotoxic agent and methods for the treatment of tumor of hematopoietic origin
US7504495B2 (en) 2003-11-20 2009-03-17 Exiqon A/S Quencher compositions comprising anthraquinone moieties
EP2363480A2 (en) 2004-01-20 2011-09-07 Isis Pharmaceuticals, Inc. Modulation of glucocorticoid receptor expression
EP2468865A1 (en) 2004-02-06 2012-06-27 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of stat3 expression
EP2527444A2 (en) 2004-02-06 2012-11-28 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of stat3 expression
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
EP2700720A2 (en) 2004-03-15 2014-02-26 Isis Pharmaceuticals, Inc. Compositions and methods for optimizing cleavage of RNA by RNASE H
US8383344B2 (en) 2004-04-07 2013-02-26 Exiqon A/S Methods for quantification of microRNAs and small interfering RNAs
US8192937B2 (en) 2004-04-07 2012-06-05 Exiqon A/S Methods for quantification of microRNAs and small interfering RNAs
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
EP1959012A2 (en) 2004-12-29 2008-08-20 Exiqon A/S Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAs and their target mRNAs
EP2813581A1 (en) 2005-01-06 2014-12-17 Applied Biosystems, LLC Polypeptides having nucleic acid binding activity and compositions and methods for nucleic acid amplification
US9267130B2 (en) 2005-01-06 2016-02-23 Applied Biosystems, Llc Polypeptides having nucleic acid binding activity and compositions and methods for nucleic acid amplification
EP2208796A2 (en) 2005-01-06 2010-07-21 Applied Biosystems, LLC Polypeptides having nucleic acid binding activity and compositions and methods for nucleic acid amplification
EP2050763A2 (en) 2005-03-10 2009-04-22 Genentech, Inc. Methods and compositions for modulating vascular integrity
US9719089B2 (en) 2005-06-14 2017-08-01 Northwestern University Nucleic acid functionalized nonoparticles for therapeutic applications
US8999947B2 (en) 2005-06-14 2015-04-07 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
US10370661B2 (en) 2005-06-14 2019-08-06 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
US8962254B2 (en) 2005-07-15 2015-02-24 Applied Biosystems, Llc Analyzing messenger RNA and micro RNA in the same reaction mixture
EP2405024A1 (en) 2005-07-15 2012-01-11 Life Technologies Corporation Hot start reverse transcription by primer design
US9422603B2 (en) 2005-07-15 2016-08-23 Applied Biosystems, Llc Analyzing messenger RNA and micro RNA in the same reaction mixture
US7745122B2 (en) 2005-07-15 2010-06-29 Applied Biosystems, Llc Analyzing messenger RNA and micro RNA in the same reaction mixture
EP2308990A1 (en) 2005-07-15 2011-04-13 Life Technologies Corporation Analyzing messenger RNA and micro RNA in the same reaction mixture
US9593374B2 (en) 2005-08-17 2017-03-14 Lianidou Evriklia Composition and method for determination of CK19 expression
WO2007027894A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Antisense compounds having enhanced anti-microrna activity
EP2338991A2 (en) 2005-08-29 2011-06-29 Regulus Therapeutics, Inc Methods for use in modulating MIR-122a
EP2338992A2 (en) 2005-08-29 2011-06-29 Regulus Therapeutics, Inc Antisense compounds having enhanced anti-microRNA activity
US9580743B2 (en) 2005-09-09 2017-02-28 Life Technologies Corporation SSB-polymerase fusion proteins
EP2458011A1 (en) 2005-10-03 2012-05-30 Life Technologies Corporation Compositions, methods, and kits for amplifying nucleic acids
EP2333115A1 (en) 2005-12-22 2011-06-15 Keygene N.V. Alternative nucleotides for improved targeted nucleotide exchange
US9127272B2 (en) 2006-01-27 2015-09-08 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of target nucleic acids
US9598693B2 (en) 2006-01-27 2017-03-21 Ionis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
EP2388328A1 (en) 2006-01-27 2011-11-23 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
EP2388327A1 (en) 2006-01-27 2011-11-23 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
WO2007106690A2 (en) 2006-03-15 2007-09-20 Siemens Healthcare Diagnostics Inc. Degenerate nucleobase analogs
EP2360277A1 (en) 2006-05-03 2011-08-24 Geisinger Clinic Methods for diagnosing and predicting non-alcoholic steatohepatitis (NASH)
EP2505648A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PTP1B
EP2505646A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of CRP
EP2505647A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of DGAT2
US8143230B2 (en) 2006-05-05 2012-03-27 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PCSK9
US8969316B2 (en) 2006-05-05 2015-03-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of DGAT2
US9045754B2 (en) 2006-05-05 2015-06-02 Isis Pharmaceuticals, Inc. Short antisense compounds with gapmer configuration
EP2505649A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of GCGR
EP2505650A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PCSK9
EP2458006A1 (en) 2006-05-05 2012-05-30 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression APOB
EP2363481A1 (en) 2006-05-05 2011-09-07 Isis Pharmaceuticals, Inc. Compounds and methods for modulating gene expression
EP2363482A1 (en) 2006-05-05 2011-09-07 Isis Pharmaceuticals, Inc. Compounds and methods for modulating gene expression
EP2397551A1 (en) 2006-05-05 2011-12-21 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PCSK9
US10370656B2 (en) 2006-06-08 2019-08-06 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
EP2484781A2 (en) 2006-08-01 2012-08-08 Applied Biosystems, LLC Detection of analytes and nucleic acids
EP3305915A1 (en) 2006-08-01 2018-04-11 Applied Biosystems, LLC Detection of analytes and nucleic acids
US9310361B2 (en) 2006-10-05 2016-04-12 Massachusetts Institute Of Technology Multifunctional encoded particles for high-throughput analysis
EP3916095A1 (en) 2006-10-18 2021-12-01 Ionis Pharmaceuticals, Inc. Antisense compounds
EP3202905A1 (en) 2006-10-18 2017-08-09 Ionis Pharmaceuticals, Inc. Antisense compounds
EP2410053A1 (en) 2006-10-18 2012-01-25 Isis Pharmaceuticals, Inc. Antisense compounds
EP2410054A1 (en) 2006-10-18 2012-01-25 Isis Pharmaceuticals, Inc. Antisense compounds
US9550988B2 (en) 2006-10-18 2017-01-24 Ionis Pharmaceuticals, Inc. Antisense compounds
US8188255B2 (en) 2006-10-20 2012-05-29 Exiqon A/S Human microRNAs associated with cancer
EP2090665A2 (en) 2006-10-20 2009-08-19 Exiqon A/S Novel human microRNAs associated with cancer
US9650636B2 (en) 2006-11-27 2017-05-16 Ionis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US11530410B2 (en) 2006-11-27 2022-12-20 Ionis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8912160B2 (en) 2006-11-27 2014-12-16 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8084437B2 (en) 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8664190B2 (en) 2006-11-27 2014-03-04 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8293684B2 (en) 2006-11-29 2012-10-23 Exiqon Locked nucleic acid reagents for labelling nucleic acids
US8048998B2 (en) 2007-01-19 2011-11-01 Exiqon A/S Mediated cellular delivery of LNA oligonucleotides
US9890427B2 (en) 2007-02-09 2018-02-13 Northwestern University Particles for detecting intracellular targets
US11155877B2 (en) 2007-04-27 2021-10-26 Quest Diagnostics Investments Llc Nucleic acid detection combining amplification with fragmentation
US9783854B2 (en) 2007-04-27 2017-10-10 Quest Diagnostics Investments Incorporated Nucleic acid detection combining amplification with fragmentation
US8999634B2 (en) 2007-04-27 2015-04-07 Quest Diagnostics Investments Incorporated Nucleic acid detection combining amplification with fragmentation
US10106857B2 (en) 2007-04-27 2018-10-23 Quest Diagnostics Investments Incorporated Nucleic acid detection combining amplification with fragmentation
US11965212B2 (en) 2007-04-27 2024-04-23 Quest Diagnostics Investments Llc Nucleic acid detection combining amplification with fragmentation
EP2826863A1 (en) 2007-05-30 2015-01-21 Northwestern University Nucleic acid functionalized nanoparticles for therapeutic applications
US9598724B2 (en) 2007-06-01 2017-03-21 Ibis Biosciences, Inc. Methods and compositions for multiple displacement amplification of nucleic acids
US7807372B2 (en) 2007-06-04 2010-10-05 Northwestern University Screening sequence selectivity of oligonucleotide-binding molecules using nanoparticle based colorimetric assay
WO2009045469A2 (en) 2007-10-02 2009-04-09 Amgen Inc. Increasing erythropoietin using nucleic acids hybridizable to micro-rna and precursors thereof
WO2009044392A2 (en) 2007-10-03 2009-04-09 Quark Pharmaceuticals, Inc. Novel sirna structures
US8017338B2 (en) 2007-11-20 2011-09-13 Life Technologies Corporation Reversible di-nucleotide terminator sequencing
US8715938B2 (en) 2007-11-20 2014-05-06 Life Technologies Corporation Reversible di-nucleotide terminator sequencing
US10365224B2 (en) 2007-12-06 2019-07-30 Genalyte, Inc. Label-free optical sensors
JPWO2009093384A1 (ja) * 2008-01-24 2011-05-26 独立行政法人産業技術総合研究所 ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法
WO2009093384A1 (ja) * 2008-01-24 2009-07-30 National Institute Of Advanced Industrial Science And Technology ポリヌクレオチド及びポリヌクレオチド類似体並びにこれらを用いた遺伝子発現制御方法
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
EP2982753A1 (en) 2008-04-18 2016-02-10 Baxter International Inc Microsphere-based composition for preventing and/or reversing new-onset autoimmune diabetes
WO2009149182A1 (en) 2008-06-04 2009-12-10 The Board Of Regents Of The University Of Texas System Modulation of gene expression through endogenous small rna targeting of gene promoters
WO2009147684A2 (en) 2008-06-06 2009-12-10 Quark Pharmaceuticals, Inc. Compositions and methods for treatment of ear disorders
WO2010014592A1 (en) 2008-07-29 2010-02-04 The Board Of Regents Of The University Of Texas Sytem Selective inhibition of polyglutamine protein expression
EP3375451A1 (en) 2008-08-25 2018-09-19 Excaliard Pharmaceuticals, Inc. Method for reducing scarring during wound healing using antisense compounds directed to ctgf
WO2010042281A2 (en) 2008-08-25 2010-04-15 Excaliard Pharmaceuticals Antisense oligonucleotides directed against connective tissue growth factor and uses thereof
WO2010027831A1 (en) 2008-08-25 2010-03-11 Excaliard Pharmaceuticals, Inc. Method for reducing scarring during wound healing using antisense compounds directed to ctgf
EP3081648A1 (en) 2008-08-25 2016-10-19 Excaliard Pharmaceuticals, Inc. Antisense oligonucleotides directed against connective tissue growth factor and uses thereof
WO2010024231A1 (ja) * 2008-08-26 2010-03-04 株式会社日立ハイテクノロジーズ 高発現遺伝子由来のcDNAクローンの含有率を低減させたcDNAライブラリーの作製方法
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
US10612086B2 (en) 2008-09-16 2020-04-07 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
US10738358B2 (en) 2008-09-16 2020-08-11 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
EP2447274A2 (en) 2008-10-24 2012-05-02 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
US11041811B2 (en) 2008-10-27 2021-06-22 Genalyte, Inc. Biosensors based on optical probing and sensing
US9846126B2 (en) 2008-10-27 2017-12-19 Genalyte, Inc. Biosensors based on optical probing and sensing
US9844562B2 (en) 2008-11-24 2017-12-19 Northwestern University Polyvalent RNA-nanoparticle compositions
US10391116B2 (en) 2008-11-24 2019-08-27 Northwestern University Polyvalent RNA-nanoparticle compositions
EP3335705A1 (en) 2008-11-24 2018-06-20 Northwestern University Polyvalent rna-nanoparticle compositions
US9139827B2 (en) 2008-11-24 2015-09-22 Northwestern University Polyvalent RNA-nanoparticle compositions
WO2010080452A2 (en) 2008-12-18 2010-07-15 Quark Pharmaceuticals, Inc. siRNA COMPOUNDS AND METHODS OF USE THEREOF
WO2010074562A1 (en) 2008-12-22 2010-07-01 Keygene N.V. Use of double stranded rna to increase the efficiency of targeted gene alteration in plant protoplasts
US11633503B2 (en) 2009-01-08 2023-04-25 Northwestern University Delivery of oligonucleotide-functionalized nanoparticles
US10098958B2 (en) 2009-01-08 2018-10-16 Northwestern University Delivery of oligonucleotide functionalized nanoparticles
US10041075B2 (en) 2009-01-14 2018-08-07 Drexel University Modulation of pre-mRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
US9885049B2 (en) 2009-01-14 2018-02-06 Drexel University Modulation of pre-MRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
US8680254B2 (en) 2009-01-14 2014-03-25 Philadelphia Health & Education Corporation Modulation of pre-mRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
US10337015B2 (en) 2009-01-14 2019-07-02 Drexel University Modulation of pre-MRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
US9359603B2 (en) 2009-01-14 2016-06-07 Drexel University Modulation of pre-mRNA using splice modulating oligonucleotides as therapeutic agents in the treatment of disease
US9096895B2 (en) 2009-02-02 2015-08-04 Exiqon A/S Method for quantification of small RNA species
WO2010091308A2 (en) 2009-02-06 2010-08-12 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010120420A1 (en) 2009-04-15 2010-10-21 Northwestern University Delivery of oligonucleotide-functionalized nanoparticles
EP3248618A1 (en) 2009-04-22 2017-11-29 Massachusetts Institute Of Technology Innate immune suppression enables repeated delivery of long rna molecules
EP3524275A1 (en) 2009-04-22 2019-08-14 Massachusetts Institute Of Technology Innate immune supression enables repeated delivery of long rna molecules
WO2010124231A2 (en) 2009-04-24 2010-10-28 The Board Of Regents Of The University Of Texas System Modulation of gene expression using oligomers that target gene regions downstream of 3' untranslated regions
WO2010135384A2 (en) 2009-05-21 2010-11-25 Siemens Healthcare Diagnostics Inc. Universal tags with non-natural nucleobases
EP3150619A1 (en) 2009-05-21 2017-04-05 Siemens Healthcare Diagnostics Inc. Universal tags with non-natural nucleobases
EP3597657A1 (en) 2009-05-21 2020-01-22 Siemens Healthcare Diagnostics Inc. Universal tags with non-natural nucleobases
EP3276004A2 (en) 2009-06-08 2018-01-31 Quark Pharmaceuticals, Inc. Methods for treating chronic kidney disease
WO2011028950A1 (en) 2009-09-02 2011-03-10 Genentech, Inc. Mutant smoothened and methods of using the same
EP3225695A1 (en) 2009-10-15 2017-10-04 Ibis Biosciences, Inc. Multiple displacement amplification
US9890408B2 (en) 2009-10-15 2018-02-13 Ibis Biosciences, Inc. Multiple displacement amplification
EP2957641A1 (en) 2009-10-15 2015-12-23 Ibis Biosciences, Inc. Multiple displacement amplification
WO2011047307A1 (en) 2009-10-15 2011-04-21 Ibis Biosciences, Inc. Multiple displacement amplification
WO2011050194A1 (en) 2009-10-22 2011-04-28 Genentech, Inc. Methods and compositions for modulating hepsin activation of macrophage-stimulating protein
WO2011056687A2 (en) 2009-10-27 2011-05-12 Swift Biosciences, Inc. Polynucleotide primers and probes
US10480030B2 (en) 2009-10-27 2019-11-19 Swift Biosciences, Inc. Polynucleotide primers and probes
WO2011052436A1 (ja) 2009-10-29 2011-05-05 国立大学法人大阪大学 架橋型人工ヌクレオシドおよびヌクレオチド
US8541562B2 (en) 2009-10-29 2013-09-24 Osaka University Bridged artificial nucleoside and nucleotide
US9376690B2 (en) 2009-10-30 2016-06-28 Northwestern University Templated nanoconjugates
US9757475B2 (en) 2009-10-30 2017-09-12 Northwestern University Templated nanoconjugates
WO2011053994A1 (en) 2009-11-02 2011-05-05 Alnylam Pharmaceuticals, Inc. Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter
WO2011056215A1 (en) 2009-11-03 2011-05-12 Landers James P Versatile, visible method for detecting polymeric analytes
WO2011063403A1 (en) 2009-11-23 2011-05-26 Swift Biosciences, Inc. Devices to extend single stranded target molecules
WO2011066503A2 (en) 2009-11-30 2011-06-03 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
EP3002297A2 (en) 2009-11-30 2016-04-06 F. Hoffmann-La Roche AG Antibodies for treating and diagnosing tumors expressing slc34a2 (tat211)
WO2011072091A1 (en) 2009-12-09 2011-06-16 Quark Pharmaceuticals, Inc. Methods and compositions for treating diseases, disorders or injury of the cns
EP2862929A1 (en) 2009-12-09 2015-04-22 Quark Pharmaceuticals, Inc. Compositions and methods for treating diseases, disorders or injury of the CNS
US9206424B2 (en) 2009-12-09 2015-12-08 Nitto Denko Corporation Modulation of HSP47 expression
EP3012324A2 (en) 2009-12-09 2016-04-27 Nitto Denko Corporation Modulation of hsp47 expression
EP3434773A2 (en) 2009-12-09 2019-01-30 Nitto Denko Corporation Modulation of hsp47 expression
US10093923B2 (en) 2009-12-09 2018-10-09 Nitto Denko Corporation Modulation of HSP47 expression
US8710209B2 (en) 2009-12-09 2014-04-29 Nitto Denko Corporation Modulation of HSP47 expression
US9926593B2 (en) 2009-12-22 2018-03-27 Sequenom, Inc. Processes and kits for identifying aneuploidy
US11180799B2 (en) 2009-12-22 2021-11-23 Sequenom, Inc. Processes and kits for identifying aneuploidy
WO2011084193A1 (en) 2010-01-07 2011-07-14 Quark Pharmaceuticals, Inc. Oligonucleotide compounds comprising non-nucleotide overhangs
WO2011085056A1 (en) 2010-01-07 2011-07-14 Quark Pharmaceuticals, Inc. Oligonucleotide compounds comprising non-nucleotide overhangs
EP3421040A1 (en) 2010-01-08 2019-01-02 Ionis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2011085271A2 (en) 2010-01-08 2011-07-14 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2011097388A1 (en) 2010-02-03 2011-08-11 Alnylam Pharmaceuticals, Inc. Selective inhibition of polyglutamine protein expression
EP3321361A1 (en) 2010-02-08 2018-05-16 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
EP3561060A1 (en) 2010-02-08 2019-10-30 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
EP3628750A1 (en) 2010-02-08 2020-04-01 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
EP3208347A1 (en) 2010-02-08 2017-08-23 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2011106297A2 (en) 2010-02-23 2011-09-01 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2011105902A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-beta (c8-beta) and uses thereof
WO2011105900A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 8-alpha (c8-alpha) and uses thereof
WO2011105901A2 (en) 2010-02-23 2011-09-01 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Antagonists of complement component 9 (c9) and uses thereof
WO2011108930A1 (en) 2010-03-04 2011-09-09 Interna Technologies Bv A MiRNA MOLECULE DEFINED BY ITS SOURCE AND ITS DIAGNOSTIC AND THERAPEUTIC USES IN DISEASES OR CONDITIONS ASSOCIATED WITH EMT
EP3214174A1 (en) 2010-03-04 2017-09-06 InteRNA Technologies B.V. A mirna molecule defined by its source and its diagnostic and therapeutic uses in diseases or conditions associated with emt
WO2011113054A2 (en) 2010-03-12 2011-09-15 Aurasense Llc Crosslinked polynucleotide structure
US8889350B2 (en) 2010-03-26 2014-11-18 Swift Biosciences, Inc. Methods and compositions for isolating polynucleotides
WO2011133695A2 (en) 2010-04-20 2011-10-27 Swift Biosciences, Inc. Materials and methods for nucleic acid fractionation by solid phase entrapment and enzyme-mediated detachment
WO2011139699A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
WO2011139695A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. Modified 5' diphosphate nucleosides and oligomeric compounds prepared therefrom
WO2011139702A2 (en) 2010-04-28 2011-11-10 Isis Pharmaceuticals, Inc. Modified nucleosides and oligomeric compounds prepared therefrom
EP3091027A1 (en) 2010-04-28 2016-11-09 Ionis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
EP3173419A1 (en) 2010-04-28 2017-05-31 Ionis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
US9061044B2 (en) 2010-04-29 2015-06-23 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression
WO2011139911A2 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Lipid formulated single stranded rna
US11535849B2 (en) 2010-04-29 2022-12-27 Ionis Pharmaceuticals, Inc. Modulation of transthyretin expression
WO2011139917A1 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression
US9399774B2 (en) 2010-04-29 2016-07-26 Ionis Pharmaceuticals, Inc. Modulation of transthyretin expression
WO2011134474A1 (en) 2010-04-30 2011-11-03 Exiqon A/S In situ hybridization method and buffer
US9212390B2 (en) 2010-04-30 2015-12-15 Exiqon A/S In situ hybridization method and buffer
US10023912B2 (en) 2010-04-30 2018-07-17 Exiqon A/S In situ hybridization method and buffer
WO2011139985A1 (en) 2010-05-03 2011-11-10 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
WO2011150226A1 (en) 2010-05-26 2011-12-01 Landers James P Method for detecting nucleic acids based on aggregate formation
US9476101B2 (en) 2010-06-07 2016-10-25 Firefly Bioworks, Inc. Scanning multifunctional particles
WO2011156278A1 (en) 2010-06-07 2011-12-15 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
US9290816B2 (en) 2010-06-07 2016-03-22 Firefly Bioworks Inc. Nucleic acid detection and quantification by post-hybridization labeling and universal encoding
WO2011156202A1 (en) 2010-06-08 2011-12-15 Isis Pharmaceuticals, Inc. Substituted 2 '-amino and 2 '-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2012005572A1 (en) 2010-07-06 2012-01-12 Interna Technologies Bv Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma, or in diseases or conditions associated with activated braf pathway
EP3369817A1 (en) 2010-07-06 2018-09-05 InteRNA Technologies B.V. Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma , or in diseases or conditions with activated braf pathway
EP2913402A1 (en) 2010-07-16 2015-09-02 Tocagen Inc. Retrovirus detection
EP3633038A2 (en) 2010-07-19 2020-04-08 Ionis Pharmaceuticals, Inc. Modulation of dystrophia myotonica-protein kinase (dmpk) expression
EP3489360A2 (en) 2010-07-19 2019-05-29 Ionis Pharmaceuticals, Inc. Modulation of nuclear-retained rna
EP3031920A1 (en) 2010-07-19 2016-06-15 Ionis Pharmaceuticals, Inc. Modulation of dystrophia myotonica-protein kinase (dmpk) expression
EP2412724A1 (en) 2010-07-29 2012-02-01 Centre National de la Recherche Scientifique (C.N.R.S) Regulation of Glypican 4 activity to modulate the fate of stem cells and uses thereof
WO2012013784A1 (en) 2010-07-29 2012-02-02 Centre National De La Recherche Scientifique (C.N.R.S) Regulation of glypican 4 activity to modulate the fate of stem cells and uses thereof
WO2012047968A2 (en) 2010-10-05 2012-04-12 Genentech, Inc. Mutant smoothened and methods of using the same
EP3266881A1 (en) 2010-11-05 2018-01-10 Genalyte, Inc. Optical analyte detection systems and methods of use
WO2012061778A2 (en) 2010-11-05 2012-05-10 Genalyte, Inc. Optical analyte detection systems and methods of use
US9921165B2 (en) 2010-11-05 2018-03-20 Genalyte, Inc. Optical analyte detection systems and methods of use
EP3733866A1 (en) 2010-11-05 2020-11-04 Genalyte, Inc. Optical analyte detection systems and methods of use
US9416360B2 (en) 2010-11-05 2016-08-16 MiRagen Therapeutics, Inc. Base modified oligonucleotides
EP3521451A1 (en) 2010-11-17 2019-08-07 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
WO2012068405A2 (en) 2010-11-17 2012-05-24 Isis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
US9150854B2 (en) 2010-12-02 2015-10-06 Keygene N.V. Targeted alteration of DNA
WO2012074385A1 (en) 2010-12-02 2012-06-07 Keygene N.V. Targeted alteration of dna
US9518258B2 (en) 2010-12-02 2016-12-13 Keygene N.V. Targeted alteration of DNA with oligonucleotides
EP2857512A1 (en) 2010-12-02 2015-04-08 Keygene N.V. Targeted alteration of DNA
WO2012074386A1 (en) 2010-12-02 2012-06-07 Keygene N.V. Targeted alteration of dna with oligonucleotides
EP2474617A1 (en) 2011-01-11 2012-07-11 InteRNA Technologies BV Mir for treating neo-angiogenesis
WO2012096523A2 (en) 2011-01-11 2012-07-19 Seegene, Inc. Detection of target nucleic acid sequences by pto cleavage and extension assay
WO2012096573A1 (en) 2011-01-11 2012-07-19 Interna Technologies B.V. Mirna for treating diseases and conditions associated with neo-angiogenesis
EP2708608A1 (en) 2011-01-11 2014-03-19 Seegene, Inc. Detection of target nucleic acid sequences by pto cleavage and extension assay
EP3543352A1 (en) 2011-01-11 2019-09-25 Seegene, Inc. Detection of target nucleic acid sequences by pto cleavage and extension assay
EP2826868A1 (en) 2011-01-11 2015-01-21 Seegene, Inc. Detection of target nucleic acid sequences by pto cleavage and extension assay
WO2012106508A1 (en) 2011-02-02 2012-08-09 Pfizer Inc. Method of treating keloids or hypertrophic scars using antisense compounds targeting connective tissue growth factor (ctgf)
US10813934B2 (en) 2011-02-02 2020-10-27 The Trustees Of Princeton University Sirtuin modulators as inhibitors of cytomegalovirus
WO2012106509A1 (en) 2011-02-02 2012-08-09 The Trustees Of Princeton University Sirtuin modulators as virus production modulators
US10017764B2 (en) 2011-02-08 2018-07-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2012109495A1 (en) 2011-02-09 2012-08-16 Metabolic Solutions Development Company, Llc Cellular targets of thiazolidinediones
US9487778B2 (en) 2011-03-03 2016-11-08 Quark Pharmaceuticals, Inc. Oligonucleotide modulators of the toll-like receptor pathway
US9796979B2 (en) 2011-03-03 2017-10-24 Quark Pharmaceuticals Inc. Oligonucleotide modulators of the toll-like receptor pathway
WO2012118911A1 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Oligonucleotide modulators of the toll-like receptor pathway
WO2012118910A2 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Compositions and methods for treating lung disease and injury
WO2012134195A2 (en) 2011-03-29 2012-10-04 Seegene, Inc. Detection of target nucleic acid sequence by pto cleavage and extension-dependent cleavage
EP3466960A2 (en) 2011-04-01 2019-04-10 Ionis Pharmaceuticals, Inc. Modulation of signal transducer and activator of transcription 3 (stat3) expression
US10188682B2 (en) 2011-04-07 2019-01-29 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
WO2012136859A1 (en) 2011-04-07 2012-10-11 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
US11975032B2 (en) 2011-04-07 2024-05-07 Medizinische Hochschule Hannover Medicament for liver regeneration and for treatment of liver failure
US9186381B2 (en) 2011-04-07 2015-11-17 Helmholtz Zentrum Fuer Infektionsforschung Gmbh Medicament for liver regeneration and for treatment of liver failure
EP3192870A1 (en) 2011-04-07 2017-07-19 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
EP2508607A1 (en) 2011-04-07 2012-10-10 Helmholtz-Zentrum für Infektionsforschung GmbH Medicament for liver regeneration and for treatment of liver failure
EP3816288A2 (en) 2011-04-21 2021-05-05 Glaxo Group Limited Modulation of hepatitis b virus (hbv) expression
EP3312189A1 (en) 2011-04-21 2018-04-25 Ionis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
EP3505528A1 (en) 2011-04-21 2019-07-03 Ionis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
WO2012149154A1 (en) 2011-04-26 2012-11-01 Swift Biosciences, Inc. Polynucleotide primers and probes
EP3357497A1 (en) 2011-04-27 2018-08-08 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein ciii (apociii) expression
WO2012149495A1 (en) 2011-04-27 2012-11-01 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein ciii (apociii) expression
EP3378954A1 (en) 2011-04-29 2018-09-26 Sequenom, Inc. Quantification of a minority nucleic acid species
WO2012149339A2 (en) 2011-04-29 2012-11-01 Sequenom, Inc. Quantification of a minority nucleic acid species
WO2012151268A1 (en) 2011-05-02 2012-11-08 University Of Virginia Patent Foundation Method and system for high throughput optical and label free detection of analytes
WO2012151289A2 (en) 2011-05-02 2012-11-08 University Of Virginia Patent Foundation Method and system to detect aggregate formation on a substrate
WO2012150835A2 (en) 2011-05-04 2012-11-08 Seegene, Inc. Detection of target nucleic acid sequences by po cleavage and hybridization
WO2012170957A2 (en) 2011-06-08 2012-12-13 Nitto Denko Corporation Retinoid-liposomes for enhancing modulation of hsp47 expression
US10195145B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Method for treating fibrosis using siRNA and a retinoid-lipid drug carrier
US8741867B2 (en) 2011-06-08 2014-06-03 Nitto Denko Corporation Retinoid-liposomes for treating fibrosis
US9456984B2 (en) 2011-06-08 2016-10-04 Nitto Denko Corporation Method for treating fibrosis using siRNA and a retinoid-lipid drug carrier
EP3075855A1 (en) 2011-06-08 2016-10-05 Nitto Denko Corporation Retinoid-liposomes for enhancing modulation of hsp47 expression
US10196637B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Retinoid-lipid drug carrier
US8664376B2 (en) 2011-06-08 2014-03-04 Nitto Denko Corporation Retinoid-liposomes for enhancing modulation of HSP47 expression
WO2012170347A1 (en) 2011-06-09 2012-12-13 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
EP3320922A1 (en) 2011-06-10 2018-05-16 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (klkb1) expression
US9315811B2 (en) 2011-06-10 2016-04-19 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
WO2012174476A2 (en) 2011-06-16 2012-12-20 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
US9322021B2 (en) 2011-06-29 2016-04-26 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
WO2013003808A1 (en) 2011-06-29 2013-01-03 Isis Pharmaceuticals, Inc. Methods for modulating kallikrein (klkb1) expression
US11732261B2 (en) 2011-08-11 2023-08-22 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
US9650421B2 (en) 2011-09-02 2017-05-16 Northwestern University Self-assembled nanostructures
EP3533873A1 (en) 2011-09-14 2019-09-04 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US10398784B2 (en) 2011-09-14 2019-09-03 Northwestern Univerity Nanoconjugates able to cross the blood-brain barrier
US9889209B2 (en) 2011-09-14 2018-02-13 Northwestern University Nanoconjugates able to cross the blood-brain barrier
WO2013040499A1 (en) 2011-09-14 2013-03-21 Northwestern University Nanoconjugates able to cross the blood-brain barrier
WO2013043817A1 (en) 2011-09-20 2013-03-28 Isis Phamaceuticals, Inc. Antisense modulation of gcgr expression
EP3401401A1 (en) 2011-09-20 2018-11-14 Ionis Pharmaceuticals, Inc. Antisense modulation of gcgr expression
WO2013063313A1 (en) 2011-10-25 2013-05-02 Isis Pharmaceuticals, Inc. Antisense modulation of gccr expression
WO2013067076A2 (en) 2011-11-03 2013-05-10 Quark Pharmaceuticals, Inc. Methods and compositions for neuroprotection
WO2013070786A1 (en) 2011-11-07 2013-05-16 Isis Pharmaceuticals, Inc. Modulation of tmprss6 expression
US9725722B2 (en) 2011-11-07 2017-08-08 Ionis Pharmaceuticals, Inc. Modulation of TMPRSS6 expression
EP3650544A1 (en) 2011-11-07 2020-05-13 Ionis Pharmaceuticals, Inc. Modulation of tmprss6 expression
WO2013090457A2 (en) 2011-12-12 2013-06-20 Oncoimmunin Inc. In vivo delivery of oligonucleotides
WO2013096837A1 (en) 2011-12-22 2013-06-27 Isis Pharmaceuticals, Inc. Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1(malat-1) expression
WO2013095132A1 (en) 2011-12-22 2013-06-27 Interna Technologies B.V. Mirna for treating head and neck cancer
US9546368B2 (en) 2011-12-22 2017-01-17 Ionis Pharmaceuticals, Inc. Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1 (MALAT-1) expression
EP3330278A1 (en) 2012-02-08 2018-06-06 Ionis Pharmaceuticals, Inc. Modulation of rna by repeat targeting
WO2013120003A1 (en) 2012-02-08 2013-08-15 Isis Pharmaceuticals, Inc. Modulation of rna by repeat targeting
US10738359B2 (en) 2012-03-02 2020-08-11 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9605313B2 (en) 2012-03-02 2017-03-28 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US11312997B2 (en) 2012-03-02 2022-04-26 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
WO2013133561A1 (en) 2012-03-05 2013-09-12 Seegene, Inc. Detection of nucleotide variation on target nucleic acid sequence by pto cleavage and extension assay
EP3907506A1 (en) 2012-03-12 2021-11-10 The Board of Trustees of the University of Illinois Optical analyte detection systems with magnetic enhancement and methods of their use
WO2013138251A1 (en) 2012-03-12 2013-09-19 The Board Of Trustes Of The University Of Illinois Optical analyte detection systems with magnetic enhancement and methods of use
WO2013138536A1 (en) 2012-03-13 2013-09-19 Swift Biosciences, Inc. Methods and compositions for size-controlled homopolymer tailing of substrate polynucleotides by a nucleic acid polymerase
US9896709B2 (en) 2012-03-13 2018-02-20 Swift Biosciences, Inc. Methods and compositions for size-controlled homopolymer tailing of substrate polynucleotides by a nucleic acid polymerase
US9610362B2 (en) 2012-03-16 2017-04-04 Valerion Therapeutics, Llc Antisense conjugates for decreasing expression of DMPK
US10238753B2 (en) 2012-03-16 2019-03-26 Valerion Therapeutics, Llc Antisense conjugates for decreasing expression of DMPK
US9340784B2 (en) 2012-03-19 2016-05-17 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
US11781135B2 (en) 2012-03-30 2023-10-10 Washington University Methods for treating Alzheimer's disease
US10273474B2 (en) 2012-03-30 2019-04-30 Washington University Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome
WO2013154798A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013154799A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleosides and oligomeric compounds prepared therefrom
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
US9914922B2 (en) 2012-04-20 2018-03-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US11566245B2 (en) 2012-04-20 2023-01-31 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US11634711B2 (en) 2012-05-17 2023-04-25 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US11859180B2 (en) 2012-05-17 2024-01-02 Ionis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US11306354B2 (en) 2012-05-21 2022-04-19 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
WO2013177248A2 (en) 2012-05-22 2013-11-28 Isis Pharmaceuticals, Inc. Modulation of enhancer rna mediated gene expression
US9518261B2 (en) 2012-05-22 2016-12-13 Ionis Pharmaceuticals, Inc. Modulation of enhancer RNA mediated gene expression
EP3825403A2 (en) 2012-05-24 2021-05-26 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein(a) expression
EP3822352A2 (en) 2012-05-24 2021-05-19 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein(a) expression
WO2013177468A2 (en) 2012-05-24 2013-11-28 Isis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein(a) expression
DE202013012241U1 (de) 2012-05-25 2016-01-18 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
EP3597749A1 (en) 2012-05-25 2020-01-22 The Regents of The University of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
EP4289948A2 (en) 2012-05-25 2023-12-13 The Regents of the University of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
EP3401400A1 (en) 2012-05-25 2018-11-14 The Regents of The University of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
DE202013012242U1 (de) 2012-05-25 2016-02-02 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
DE202013012240U1 (de) 2012-05-25 2016-02-02 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
EP3241902A1 (en) 2012-05-25 2017-11-08 The Regents of The University of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
WO2014004572A2 (en) 2012-06-25 2014-01-03 Isis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
EP3770258A1 (en) 2012-06-25 2021-01-27 Ionis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
US9617539B2 (en) 2012-06-25 2017-04-11 Ionis Pharmaceuticals, Inc. Modulation of UBE3A-ATS expression
EP3461895A1 (en) 2012-06-25 2019-04-03 Ionis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
US11332791B2 (en) 2012-07-13 2022-05-17 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
EP3354750A1 (en) 2012-07-18 2018-08-01 Siemens Healthcare Diagnostics Inc. Kit of normalizing biological samples
WO2014018930A1 (en) 2012-07-27 2014-01-30 Isis Pharmaceuticals. Inc. Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen
EP3693460A1 (en) 2012-07-27 2020-08-12 Ionis Pharmaceuticals, Inc. Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen
US9403865B2 (en) 2012-08-15 2016-08-02 Ionis Pharmaceuticals, Inc. Method of preparing oligomeric compounds using modified capping protocols
EP3421602A1 (en) 2012-09-06 2019-01-02 The University of Chicago Antisense polynucleotides to induce exon skipping and methods of treating dystrophies
US9777271B2 (en) 2012-09-06 2017-10-03 The University Of Chicago Antisense polynucleotides to induce exon skipping and methods of treating dystrophies
WO2014039916A1 (en) 2012-09-06 2014-03-13 The University Of Chicago Antisense polynucleotides to induce exon skipping and methods of treating dystrophies
US9499817B2 (en) 2012-09-06 2016-11-22 The University Of Chicago Antisense polynucleotides to induce exon skipping and methods of treating dystrophies
WO2014045126A2 (en) 2012-09-18 2014-03-27 Uti Limited Partnership Treatment of pain by inhibition of usp5 de-ubiquitinase
WO2014046212A1 (ja) 2012-09-21 2014-03-27 国立大学法人大阪大学 グアニジン架橋を有する人工ヌクレオシドおよびオリゴヌクレオチド
KR20150056647A (ko) 2012-09-21 2015-05-26 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 구아니딘 가교를 갖는 인공 뉴클레오시드 및 올리고뉴클레오티드
US9523094B2 (en) 2012-10-11 2016-12-20 Ionis Pharmaceuticals, Inc. Methods of treating kennedy's disease
US9695418B2 (en) 2012-10-11 2017-07-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
WO2014059238A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals Inc Modulation of androgen receptor expression
EP4052709A1 (en) 2012-10-11 2022-09-07 Ionis Pharmaceuticals, Inc. Methods of treating kennedy's disease
WO2014062686A1 (en) 2012-10-15 2014-04-24 Isis Pharmaceuticals, Inc. Methods for modulating c9orf72 expression
US10443052B2 (en) 2012-10-15 2019-10-15 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
US10577604B2 (en) 2012-10-15 2020-03-03 Ionis Pharmaceuticals, Inc. Methods for monitoring C9ORF72 expression
US9963699B2 (en) 2012-10-15 2018-05-08 Ionis Pharmaceuticals, Inc. Methods for modulating C9ORF72 expression
US9029335B2 (en) 2012-10-16 2015-05-12 Isis Pharmaceuticals, Inc. Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2014070868A1 (en) 2012-10-31 2014-05-08 Isis Pharmaceuticals Inc Cancer treatment
EP3483273A1 (en) 2012-10-31 2019-05-15 Ionis Pharmaceuticals, Inc. Cancer treatment
EP3800256A1 (en) 2012-11-06 2021-04-07 InteRNA Technologies B.V. Combination to be used in therapeutic use against diseases or conditions associated with melanoma, or in diseases or conditions associated with activated b-raf pathway
WO2014072357A1 (en) 2012-11-06 2014-05-15 Interna Technologies B.V. Combination for use in treating diseases or conditions associated with melanoma, or treating diseases or conditions associated with activated b-raf pathway
WO2014076196A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Anti apob antisense conjugate compounds
US10077443B2 (en) 2012-11-15 2018-09-18 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
US11155816B2 (en) 2012-11-15 2021-10-26 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
WO2014076195A1 (en) 2012-11-15 2014-05-22 Santaris Pharma A/S Oligonucleotide conjugates
EP3406718A1 (en) 2012-11-15 2018-11-28 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
WO2014080004A1 (en) 2012-11-26 2014-05-30 Santaris Pharma A/S Compositions and methods for modulation of fgfr3 expression
WO2014113540A1 (en) 2013-01-16 2014-07-24 Iowa State University Research Foundation, Inc. A deep intronic target for splicing correction on spinal muscular atrophy gene
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
WO2014118267A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Lna oligonucleotide carbohydrate conjugates
US9701708B2 (en) 2013-01-31 2017-07-11 Ionis Pharmaceuticals, Inc. Method of preparing oligomeric compounds using modified coupling protocols
EP3400947A1 (en) 2013-02-14 2018-11-14 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein c-iii (apociii) expression in lipoprotein lipase deficient (lpld) populations
WO2014126229A1 (ja) 2013-02-18 2014-08-21 塩野義製薬株式会社 含窒素複素環構造を有するヌクレオシド及びヌクレオチド
US9315535B2 (en) 2013-02-18 2016-04-19 Shionogi & Co., Ltd. Nucleoside and nucleotide having nitrogen-containing heterocycle structure
EP2770065A1 (en) 2013-02-25 2014-08-27 Seegene, Inc. Detection of nucleotide variation on target nucleic acid sequence
WO2014134144A1 (en) 2013-02-28 2014-09-04 The General Hospital Corporation Mirna profiling compositions and methods of use
WO2014134179A1 (en) 2013-02-28 2014-09-04 The Board Of Regents Of The University Of Texas System Methods for classifying a cancer as susceptible to tmepai-directed therapies and treating such cancers
US11060145B2 (en) 2013-03-13 2021-07-13 Sequenom, Inc. Methods and compositions for identifying presence or absence of hypermethylation or hypomethylation locus
WO2014142575A1 (en) 2013-03-13 2014-09-18 Seegene, Inc. Quantification of target nucleic acid using melting peak analysis
WO2014152659A1 (en) 2013-03-14 2014-09-25 Shire Human Genetic Therapies, Inc. Quantitative assessment for cap efficiency of messenger rna
WO2014152673A1 (en) 2013-03-14 2014-09-25 Shire Human Genetic Therapies, Inc. Quantitative assessment for cap efficiency of messenger rna
EP3495505A1 (en) 2013-03-14 2019-06-12 Translate Bio, Inc. Quantitative assessment for cap efficiency of messenger rna
US11155815B2 (en) 2013-03-14 2021-10-26 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Tau expression
US9644207B2 (en) 2013-03-14 2017-05-09 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Tau expression
US9983206B2 (en) 2013-03-15 2018-05-29 The Board Of Trustees Of The University Of Illinois Methods and compositions for enhancing immunoassays
US10739340B2 (en) 2013-03-15 2020-08-11 The Board Of Trustees Of The University Of Illinois Methods and compositions for enhancing immunoassays
WO2014176259A1 (en) 2013-04-22 2014-10-30 Icahn School Of Medicine At Mount Sinai Mutations in pdgfrb and notch3 as causes of autosomal dominant infantile myofibromatosis
WO2014179335A1 (en) 2013-04-29 2014-11-06 Memorial Sloan Kettering Cancer Center Compositions and methods for altering second messenger signaling
US11851655B2 (en) 2013-05-01 2023-12-26 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
US10883104B2 (en) 2013-05-01 2021-01-05 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
US9932581B2 (en) 2013-05-01 2018-04-03 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein C-III expression
US9957504B2 (en) 2013-05-01 2018-05-01 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
WO2014197938A1 (en) 2013-06-13 2014-12-18 Antisense Therapeutics Ltd Combination therapy
WO2014205449A2 (en) 2013-06-21 2014-12-24 Isis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
US9909124B2 (en) 2013-06-21 2018-03-06 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein C-III expression for improving a diabetic profile
EP3656386A1 (en) 2013-06-21 2020-05-27 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
EP3591054A1 (en) 2013-06-27 2020-01-08 Roche Innovation Center Copenhagen A/S Antisense oligomers and conjugates targeting pcsk9
EP3730614A2 (en) 2013-07-02 2020-10-28 Ionis Pharmaceuticals, Inc. Modulators of growth hormone receptor
WO2015002971A2 (en) 2013-07-02 2015-01-08 Isis Pharmaceuticals, Inc. Modulators of growth hormone receptor
WO2015008985A1 (en) 2013-07-15 2015-01-22 Seegene, Inc. Detection of target nucleic acid sequence by pto cleavage and extension-dependent immobilized oligonucleotide hybridization
EP3910060A1 (en) 2013-07-19 2021-11-17 Biogen MA Inc. Compositions for modulating tau expression
US10793856B2 (en) 2013-07-19 2020-10-06 Biogen Ma Inc. Compositions for modulating Tau expression
US11591595B2 (en) 2013-07-19 2023-02-28 Biogen Ma Inc. Compositions for modulating Tau expression
US9683235B2 (en) 2013-07-19 2017-06-20 Ionis Pharmaceuticals, Inc. Compositions for modulating Tau expression
WO2015010135A2 (en) 2013-07-19 2015-01-22 Isis Pharmaceuticals, Inc. Compositions for modulating tau expression
WO2015021457A2 (en) 2013-08-09 2015-02-12 Isis Pharmaceuticals, Inc. Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression
EP3995580A2 (en) 2013-08-09 2022-05-11 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of dystrophia myotonica-protein kinase (dmpk) expression
US9670492B2 (en) 2013-08-28 2017-06-06 Ionis Pharmaceuticals, Inc. Modulation of prekallikrein (PKK) expression
EP3715457A2 (en) 2013-08-28 2020-09-30 Ionis Pharmaceuticals, Inc. Modulation of prekallikrein (pkk) expression
WO2015031679A2 (en) 2013-08-28 2015-03-05 Isis Pharmaceuticals, Inc. Modulation of prekallikrein (pkk) expression
US11053500B2 (en) 2013-08-28 2021-07-06 lonis Pharmaceuticals, Inc. Modulation of prekallikrein (PKK) expression
US11840686B2 (en) 2013-08-28 2023-12-12 Ionis Pharmaceuticals, Inc. Modulation of prekallikrein (PKK) expression
EP3603677A1 (en) 2013-09-13 2020-02-05 Ionis Pharmaceuticals, Inc. Modulators of complement factor b
EP4166667A2 (en) 2013-10-11 2023-04-19 Ionis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
US10221414B2 (en) 2013-10-11 2019-03-05 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
US11339393B2 (en) 2013-10-11 2022-05-24 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
WO2015057998A1 (en) 2013-10-16 2015-04-23 The University Of British Columbia Device for formulating particles at small volumes
WO2015057008A2 (en) 2013-10-18 2015-04-23 Seegene, Inc. Detection of target nucleic acid sequence on solid phase by pto cleavage and extension using hcto assay
US10301622B2 (en) 2013-11-04 2019-05-28 Northwestern University Quantification and spatio-temporal tracking of a target using a spherical nucleic acid (SNA)
EP3760719A1 (en) 2013-11-18 2021-01-06 CRISPR Therapeutics AG Crispr-cas system materials and methods
EP3375877A1 (en) 2013-11-18 2018-09-19 Crispr Therapeutics AG Crispr-cas system materials and methods
US10792251B2 (en) 2013-12-03 2020-10-06 Northwestern University Liposomal particles, methods of making same and uses thereof
US11883535B2 (en) 2013-12-03 2024-01-30 Northwestern University Liposomal particles, methods of making same and uses thereof
US10182988B2 (en) 2013-12-03 2019-01-22 Northwestern University Liposomal particles, methods of making same and uses thereof
US9205102B2 (en) 2013-12-06 2015-12-08 The University Of British Columbia Method for treatment of castration-resistant prostate cancer
US10385388B2 (en) 2013-12-06 2019-08-20 Swift Biosciences, Inc. Cleavable competitor polynucleotides
EP3835419A1 (en) 2013-12-12 2021-06-16 The Regents of The University of California Methods and compositions for modifying a single stranded target nucleic acid
EP3770259A1 (en) 2013-12-24 2021-01-27 Ionis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2015100394A1 (en) 2013-12-24 2015-07-02 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US11118183B2 (en) 2013-12-24 2021-09-14 Ionis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2015120075A2 (en) 2014-02-04 2015-08-13 Genentech, Inc. Mutant smoothened and methods of using the same
WO2015125783A1 (ja) * 2014-02-18 2015-08-27 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
JPWO2015125783A1 (ja) * 2014-02-18 2017-03-30 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
US11365447B2 (en) 2014-03-13 2022-06-21 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US10036019B2 (en) 2014-03-17 2018-07-31 Ionis Pharmaceuticals, Inc. Bicyclic carbocyclic nucleosides and oligomeric compounds prepared therefrom
WO2015143246A1 (en) 2014-03-19 2015-09-24 Isis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
EP3978610A2 (en) 2014-03-19 2022-04-06 Ionis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
EP4137573A2 (en) 2014-04-01 2023-02-22 Biogen MA Inc. Compositions for modulating sod-1 expression
EP3757214A1 (en) 2014-04-01 2020-12-30 Biogen MA Inc. Compositions for modulating sod-1 expression
WO2015153800A2 (en) 2014-04-01 2015-10-08 Isis Pharmaceuticals, Inc. Compositions for modulating sod-1 expression
US10221416B2 (en) 2014-04-24 2019-03-05 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising alpha-beta-constrained nucleic acid
WO2015164693A1 (en) 2014-04-24 2015-10-29 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising alpha-beta-constrained nucleic acid
US10875884B2 (en) 2014-05-01 2020-12-29 Isis Pharmaceuticals, Inc. Compositions and methods for modulating angiopoietin-like 3 expression
EP3608406A1 (en) 2014-05-01 2020-02-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
EP3845547A1 (en) 2014-05-01 2021-07-07 Ionis Pharmaceuticals, Inc. Galnac3 conjugated modified oligonucleotide for modulating angiopoietin-like 3 expression
US9994855B2 (en) 2014-05-01 2018-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
EP3862362A2 (en) 2014-05-01 2021-08-11 Ionis Pharmaceuticals, Inc. Conjugates of modified antisense oligonucleotides and their use for modulating pkk expression
US9382540B2 (en) 2014-05-01 2016-07-05 Isis Pharmaceuticals, Inc Compositions and methods for modulating angiopoietin-like 3 expression
US11312964B2 (en) 2014-05-01 2022-04-26 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
EP3757215A2 (en) 2014-05-01 2020-12-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
EP3974534A1 (en) 2014-05-01 2022-03-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
US10294477B2 (en) 2014-05-01 2019-05-21 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating PKK expression
US10793862B2 (en) 2014-05-01 2020-10-06 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
US11613752B2 (en) 2014-05-01 2023-03-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating PKK expression
EP4219718A2 (en) 2014-05-01 2023-08-02 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating complement factor b expression
US11957788B2 (en) 2014-06-04 2024-04-16 Exicure Operating Company Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
WO2015190922A1 (en) 2014-06-10 2015-12-17 Erasmus University Medical Center Rotterdam Antisense oligonucleotides useful in treatment of pompe disease
EP4039807A1 (en) 2014-06-10 2022-08-10 Erasmus University Rotterdam Medical Center Antisense oligonucleotides useful in treatment of pompe disease
WO2016006697A1 (ja) * 2014-07-10 2016-01-14 賢二 中野 アンチセンス抗悪性腫瘍剤
JPWO2016006697A1 (ja) * 2014-07-10 2017-04-27 賢二 中野 アンチセンス抗悪性腫瘍剤
WO2016017422A1 (ja) * 2014-07-31 2016-02-04 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
JPWO2016017422A1 (ja) * 2014-07-31 2017-05-25 国立大学法人大阪大学 架橋型ヌクレオシドおよびヌクレオチド
WO2016028940A1 (en) 2014-08-19 2016-02-25 Northwestern University Protein/oligonucleotide core-shell nanoparticle therapeutics
WO2016027168A2 (en) 2014-08-20 2016-02-25 Lifesplice Pharma Llc Splice modulating oligonucleotides and methods of use thereof
US10159719B2 (en) 2014-08-21 2018-12-25 Omrix Biopharmaceuticals Ltd. Kit with stabilized thrombin
WO2016027263A2 (en) 2014-08-21 2016-02-25 Omrix Biopharmaceuticals Ltd. Stabilized thrombin
US11229688B2 (en) 2014-08-21 2022-01-25 Omrix Biopharmaceuticals Ltd. Stabilized thrombin
EP3754017A2 (en) 2014-08-21 2020-12-23 Omrix Biopharmaceuticals Ltd. Stabilized thrombin
WO2016033424A1 (en) 2014-08-29 2016-03-03 Genzyme Corporation Methods for the prevention and treatment of major adverse cardiovascular events using compounds that modulate apolipoprotein b
WO2016034611A1 (en) 2014-09-02 2016-03-10 Max-Delbrück-Centrum für Molekulare Medizin Antisense oligonucleotides targeting 3'utr region of a20
WO2016054032A1 (en) 2014-09-29 2016-04-07 The Jackson Laboratory High efficiency, high throughput generation of genetically modified mammals by electroporation
US11098309B2 (en) 2014-10-14 2021-08-24 The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone Compositions and methods for reactivating latent immunodeficiency virus
US10351853B2 (en) 2014-10-14 2019-07-16 The J. David Gladstone Institutes Compositions and methods for reactivating latent immunodeficiency virus
US11807852B2 (en) 2014-10-14 2023-11-07 The J. David Gladstone Institutes Compositions and methods for reactivating latent immunodeficiency virus
WO2016075584A1 (en) 2014-11-10 2016-05-19 Glaxosmithkline Intellectual Property (No.2) Limited Combination long acting compositions and methods for hepatitis c
WO2016075583A1 (en) 2014-11-10 2016-05-19 Glaxosmithkline Intelle Ctual Property (No.2) Limited Long acting pharmaceutical compositions for hepatitis c
WO2016081911A2 (en) 2014-11-21 2016-05-26 Northwestern University The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates
US11213593B2 (en) 2014-11-21 2022-01-04 Northwestern University Sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates
US10400243B2 (en) 2014-11-25 2019-09-03 Ionis Pharmaceuticals, Inc. Modulation of UBE3A-ATS expression
WO2016100716A1 (en) 2014-12-18 2016-06-23 Vasant Jadhav Reversirtm compounds
US9688707B2 (en) 2014-12-30 2017-06-27 Ionis Pharmaceuticals, Inc. Bicyclic morpholino compounds and oligomeric compounds prepared therefrom
WO2016126972A1 (en) 2015-02-04 2016-08-11 Genentech, Inc. Mutant smoothened and methods of using the same
WO2016138353A1 (en) 2015-02-26 2016-09-01 Ionis Pharmaceuticals, Inc. Allele specific modulators of p23h rhodopsin
EP4056703A1 (en) 2015-03-03 2022-09-14 Ionis Pharmaceuticals, Inc. Methods for modulating mecp2 expression
WO2016141236A1 (en) 2015-03-03 2016-09-09 Ionis Pharmaceuticals, Inc. Compositions for modulating mecp2 expression
US10415038B2 (en) 2015-04-03 2019-09-17 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating TMPRSS6 expression
US10801029B2 (en) 2015-04-08 2020-10-13 The University Of Chicago Compositions and methods for correcting limb girdle muscular dystrophy type 2C using exon skipping
US10273483B2 (en) 2015-04-08 2019-04-30 The University Of Chicago Compositions and methods for correcting limb girdle muscular dystrophy type 2C using exon skipping
WO2016164602A1 (en) 2015-04-08 2016-10-13 The University Of Chicago Compositions and methods for correcting limb girdle muscular dystrophy type 2c using exon skipping
US9605263B2 (en) 2015-04-16 2017-03-28 Ionis Pharmaceuticals, Inc. Compositions for modulating C9ORF72 expression
EP3722424A1 (en) 2015-04-16 2020-10-14 Ionis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
WO2016168592A2 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
WO2016196655A1 (en) 2015-06-03 2016-12-08 The Regents Of The University Of California Cas9 variants and methods of use thereof
WO2017015109A1 (en) 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
EP3919619A1 (en) 2015-07-17 2021-12-08 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
WO2017018360A1 (ja) * 2015-07-24 2017-02-02 日産化学工業株式会社 人工ヌクレオシド及び人工ヌクレオチド並びに人工オリゴヌクレオチド
WO2017023861A1 (en) 2015-08-03 2017-02-09 The Regents Of The University Of California Compositions and methods for modulating abhd2 activity
WO2017032726A1 (en) 2015-08-24 2017-03-02 Roche Innovation Center Copenhagen A/S Lna-g process
US11591594B2 (en) 2015-08-24 2023-02-28 Roche Innovation Center Copenhagen A/S LNA-G process
US10961269B2 (en) 2015-09-18 2021-03-30 Mitsubishi Tanabe Pharma Corporation Bridged nucleic acid GuNA, method for producing same, and intermediate compound
JPWO2017047816A1 (ja) * 2015-09-18 2018-07-05 田辺三菱製薬株式会社 架橋型核酸ＧｕＮＡ、その製造方法および中間体化合物
WO2017047816A1 (ja) * 2015-09-18 2017-03-23 田辺三菱製薬株式会社 架橋型核酸ＧｕＮＡ、その製造方法および中間体化合物
JP2022033869A (ja) * 2015-09-18 2022-03-02 田辺三菱製薬株式会社 架橋型核酸ＧｕＮＡ、その製造方法および中間体化合物
EP3974436A1 (en) 2015-09-18 2022-03-30 Mitsubishi Tanabe Pharma Corporation Crosslinked nucleic acid guna method for producing same, and intermediate compound
WO2017064546A1 (en) 2015-09-24 2017-04-20 Crispr Therapeutics Ag Novel family of rna-programmable endonucleases and their uses in genome editing and other applications
US10912792B2 (en) 2015-10-08 2021-02-09 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
WO2017075421A1 (en) 2015-10-29 2017-05-04 Temple University-Of The Commonwealth System Of Higher Education Modification of 3' terminal ends of nucleic acids by dna polymerase theta
US11260073B2 (en) 2015-11-02 2022-03-01 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating C90RF72
WO2017079442A1 (en) 2015-11-04 2017-05-11 Icahn School Of Medicine At Mount Sinai Methods of treating tumors and cancer, and identifying candidate subjects for such treatment
US11319536B2 (en) 2015-11-06 2022-05-03 Ionis Pharmacueticals, Inc. Modulating apolipoprotein (a) expression
US10557137B2 (en) 2015-11-06 2020-02-11 Ionis Pharmaceuticals, Inc. Modulating apolipoprotein (a) expression
US10739332B2 (en) 2015-11-12 2020-08-11 Hoffmann-La Roche Inc. Oligonucleotides for inducing paternal UBE3A expression
EP4220360A2 (en) 2015-11-12 2023-08-02 F. Hoffmann-La Roche AG Oligonucleotides for inducing paternal ube3a expression
US11852627B2 (en) 2015-11-12 2023-12-26 Hoffmann-La Roche Inc. Oligonucleotides for inducing paternal UBE3A expression
US10718753B2 (en) 2015-11-12 2020-07-21 Hoffman-La Roche Inc. Oligonucleotides for inducing paternal UBE3A expression
EP3798307A1 (en) 2015-11-12 2021-03-31 F. Hoffmann-La Roche AG Oligonucleotides for inducing paternal ube3a expression
US10494633B2 (en) 2015-11-12 2019-12-03 Roche Innovation Center Copenhagen A/S Oligonucleotides for inducing paternal UBE3A expression
US11320421B2 (en) 2015-11-12 2022-05-03 Hoffmann-La Roche Inc. Oligonucleotides for inducing paternal UBE3A expression
US11667903B2 (en) 2015-11-23 2023-06-06 The Regents Of The University Of California Tracking and manipulating cellular RNA via nuclear delivery of CRISPR/CAS9
WO2017099579A1 (en) 2015-12-07 2017-06-15 Erasmus University Medical Center Rotterdam Enzymatic replacement therapy and antisense therapy for pompe disease
EP3656872A1 (en) 2015-12-09 2020-05-27 Novartis AG Label-free analysis of rna capping efficiency using rnase h, probes and liquid chromatography/mass spectrometry
WO2017098468A1 (en) 2015-12-09 2017-06-15 Novartis Ag Label-free analysis of rna capping efficiency using rnase h, probes and liquid chromatography/mass spectrometry
WO2017109679A1 (en) 2015-12-21 2017-06-29 Novartis Ag Compositions and methods for decreasing tau expression
EP3797860A1 (en) 2016-01-06 2021-03-31 The University of British Columbia Bifurcating mixers and methods of their use and manufacture
WO2017124086A1 (en) 2016-01-15 2017-07-20 The Jackson Laboratory Genetically modified non-human mammals by multi-cycle electroporation of cas9 protein
US11530409B2 (en) 2016-01-26 2022-12-20 Nissan Chemical Corporation Single-stranded oligonucleotide
WO2017136558A1 (en) 2016-02-04 2017-08-10 Curis, Inc. Mutant smoothened and methods of using the same
EP4015647A1 (en) 2016-02-26 2022-06-22 The Board of Trustees of the Leland Stanford Junior University Multiplexed single molecule rna visualization with a two-probe proximity ligation system
EP4354140A2 (en) 2016-02-26 2024-04-17 The Board of Trustees of the Leland Stanford Junior University Multiplexed single molecule rna visualization with a two-probe proximity ligation system
WO2017147483A1 (en) 2016-02-26 2017-08-31 The Board Of Trustees Of The Leland Stanford Junior University Multiplexed single molecule rna visualization with a two-probe proximity ligation system
WO2017157899A1 (en) 2016-03-14 2017-09-21 F. Hoffmann-La Roche Ag Oligonucleotides for reduction of pd-l1 expression
US10745480B2 (en) 2016-03-14 2020-08-18 Hoffmann-La Roche, Inc. Oligonucleotides for reduction of PD-L1 expression
US11466081B2 (en) 2016-03-14 2022-10-11 Hoffmann-La Roche Inc. Oligonucleotides for reduction of PD-L1 expression
EP3786297A1 (en) 2016-03-14 2021-03-03 F. Hoffmann-La Roche AG Oligonucleotides for reduction of pd-l1 expression
US10829555B2 (en) 2016-03-14 2020-11-10 Hoffman-La Roche Inc. Oligonucleotides for reduction of PD-L1 expression
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
US11248019B2 (en) 2016-04-14 2022-02-15 Hoffmann-La Roche Inc. Trityl-mono-GalNAc compounds and their use
WO2017189730A1 (en) 2016-04-26 2017-11-02 Icahn School Of Medicine At Mount Sinai Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment
US11708614B2 (en) 2016-06-15 2023-07-25 Streck Llc Assays and methods for determining microbial resistance
DE212017000056U1 (de) 2016-06-16 2018-11-21 The Regents Of The University Of California Kits zum Nachweisen einer Target-RNA in einer Probe
DE212017000061U1 (de) 2016-06-16 2018-12-04 The Regents Of The University Of California Zusammensetzung zum Nachweis einer einzelsträngigen Target-RNA
DE212017000062U1 (de) 2016-06-16 2018-11-29 The Regents Of The University Of California Verwendung zum Nachweis einer einzelsträngigen Target-RNA
EP4036249A1 (en) 2016-06-16 2022-08-03 The Regents of the University of California Methods and compositions for detecting a target rna
WO2017218573A1 (en) 2016-06-16 2017-12-21 The Regents Of The University Of California Methods and compositions for detecting a target rna
US11191775B2 (en) 2016-06-17 2021-12-07 Hoffmann-La Roche Inc. PAPD5 and PAPD7 inhibitors for treating a hepatitis B infection
US11534452B2 (en) 2016-06-17 2022-12-27 Hoffmann-La Roche Inc. Nucleic acid molecules for reduction of PAPD5 or PAPD7 mRNA for treating hepatitis B infection
WO2017216390A1 (en) 2016-06-17 2017-12-21 F. Hoffmann-La Roche Ag Nucleic acid molecules for reduction of papd5 or papd7 mrna for treating hepatitis b infection
US10519450B2 (en) 2016-07-01 2019-12-31 Hoffmann-La Roche Inc. Antisense oligonucleotides for modulating HTRA1 expression
WO2018002105A1 (en) 2016-07-01 2018-01-04 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
WO2018026282A1 (en) 2016-08-05 2018-02-08 Erasmus University Medical Center Rotterdam (Erasmus Mc) Antisense oligomeric compound for pompe disease
WO2018026284A1 (en) 2016-08-05 2018-02-08 Erasmus University Medical Center Rotterdam (Erasmus Mc) Natural cryptic exon removal by pairs of antisense oligonucleotides
WO2018231060A1 (en) 2016-08-05 2018-12-20 Erasmus University Medical Center Rotterdam Enzymatic replacement therapy and antisense therapy for pompe disease
US11364304B2 (en) 2016-08-25 2022-06-21 Northwestern University Crosslinked micellar spherical nucleic acids
WO2018044239A1 (en) 2016-09-01 2018-03-08 Agency For Science, Technology And Research Method of treating cancer by antisense oligonucleotides targeting prdm15
US11053498B2 (en) 2016-09-29 2021-07-06 Biogen Ma Inc. Compounds and methods for reducing Tau expression
US10407680B2 (en) 2016-09-29 2019-09-10 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing Tau expression
WO2018080393A1 (en) 2016-10-28 2018-05-03 Agency For Science, Technology And Research Antisense oligonucleotides
WO2018087200A1 (en) 2016-11-11 2018-05-17 Roche Innovation Center Copenhagen A/S Therapeutic oligonucleotides capture and detection
WO2018130583A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
WO2018130582A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
WO2018130584A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
WO2018130585A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
WO2018130581A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
WO2018143475A1 (ja) 2017-02-06 2018-08-09 日産化学工業株式会社 一本鎖オリゴヌクレオチド
US11572558B2 (en) 2017-02-06 2023-02-07 Nissan Chemical Corporation Single-stranded oligonucleotide
WO2018181428A1 (ja) 2017-03-29 2018-10-04 塩野義製薬株式会社 核酸医薬及び多分岐脂質の複合体
US11453891B2 (en) 2017-05-10 2022-09-27 The Regents Of The University Of California Directed editing of cellular RNA via nuclear delivery of CRISPR/CAS9
WO2018220034A1 (en) 2017-06-01 2018-12-06 F. Hoffmann-La Roche Ag Antisense oligonucleotides for modulating htra1 expression
US11690920B2 (en) 2017-07-13 2023-07-04 Northwestern University General and direct method for preparing oligonucleotide-functionalized metal-organic framework nanoparticles
US11555188B2 (en) 2017-07-26 2023-01-17 Nissan Chemical Corporation Single-stranded oligonucleotide
WO2019022196A1 (ja) 2017-07-26 2019-01-31 日産化学株式会社 一本鎖オリゴヌクレオチド
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
US11591645B2 (en) 2017-08-31 2023-02-28 Seegene, Inc. Evaluation of performance of components using a pair of dimer-forming primers
WO2019045075A1 (ja) 2017-08-31 2019-03-07 田辺三菱製薬株式会社 Ｉｌ－３３アンタゴニストを含む子宮内膜症治療剤
WO2019066461A2 (en) 2017-09-29 2019-04-04 Seegene, Inc. DETECTION OF TARGET NUCLEIC ACID SEQUENCES BY CLEAVAGE ANALYSIS AND EXTENSION OF PTO
WO2019073018A1 (en) 2017-10-13 2019-04-18 Roche Innovation Center Copenhagen A/S METHODS OF IDENTIFYING ANTISENSE OLIGONUCLEOTIDE IMPROVED OLIGONUCLEOTIDE PHOSPHOROTHIOATE STEREODEFINIS VARIANTS USING PARTIALLY STEREODEFINIS OLIGONUCLEOTIDE SUB LIBRARIES
WO2019076842A1 (en) 2017-10-16 2019-04-25 F. Hoffmann-La Roche Ag NUCLEIC ACID MOLECULE FOR THE REDUCTION OF PAPD5 AND PAPD7 MRNA FOR THE TREATMENT OF HEPATITIS B INFECTION
US11484546B2 (en) 2017-10-16 2022-11-01 Hoffman-La Roche Inc. Nucleic acid molecule for reduction of PAPD5 and PAPD7 mRNA for treating hepatitis B infection
US10953034B2 (en) 2017-10-16 2021-03-23 Hoffmann-La Roche Inc. Nucleic acid molecule for reduction of PAPD5 and PAPD7 mRNA for treating hepatitis B infection
WO2019086603A1 (en) 2017-11-03 2019-05-09 Interna Technologies B.V. Mirna molecule, equivalent, antagomir, or source thereof for treating and/or diagnosing a condition and/or a disease associated with neuronal deficiency or for neuronal (re)generation
WO2019115416A2 (en) 2017-12-11 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
WO2019118935A1 (en) 2017-12-14 2019-06-20 Casebia Therapeutics Limited Liability Partnership Novel rna-programmable endonuclease systems and their use in genome editing and other applications
WO2019116346A1 (en) 2017-12-15 2019-06-20 Novartis Ag Polya tail length analysis of rna by mass spectrometry
WO2019121838A1 (en) 2017-12-21 2019-06-27 F. Hoffmann-La Roche Ag Companion diagnostic for htra1 rna antagonists
EP4092117A1 (en) 2017-12-22 2022-11-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
US11597926B2 (en) 2017-12-22 2023-03-07 Roche Innovation Center Copenhagen A/S Thiophosphoramidites
WO2019122277A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
WO2019122279A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorodithioate internucleoside linkage
WO2019122282A1 (en) 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
WO2019137883A1 (en) 2018-01-10 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
WO2019137974A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating gsk3b expression
WO2019140236A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
US11447775B2 (en) 2018-01-12 2022-09-20 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2019138057A1 (en) 2018-01-12 2019-07-18 Roche Innovation Center Copenhagen A/S Alpha-synuclein antisense oligonucleotides and uses thereof
WO2019140231A1 (en) 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
US11359197B2 (en) 2018-01-12 2022-06-14 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2019141656A1 (en) 2018-01-17 2019-07-25 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
WO2019141723A1 (en) 2018-01-18 2019-07-25 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting srebp1
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
WO2019154979A1 (en) 2018-02-09 2019-08-15 Genentech, Inc. Oligonucleotides for modulating tmem106b expression
WO2019155094A1 (en) 2018-02-12 2019-08-15 Interna Technologies B.V. Anticancer microrna and lipid formulations thereof
US11058767B2 (en) 2018-02-21 2021-07-13 Bristol-Myers Squibb Company CAMK2D antisense oligonucleotides and uses thereof
WO2019165067A1 (en) 2018-02-21 2019-08-29 Bristol-Myers Squibb Company Camk2d antisense oligonucleotides and uses thereof
WO2019183150A1 (en) 2018-03-19 2019-09-26 Casebia Therapeutics Limited Liability Partnership Novel rna-programmable endonuclease systems and uses thereof
WO2019182037A1 (ja) 2018-03-20 2019-09-26 国立大学法人東京工業大学 毒性が低減されたアンチセンスオリゴヌクレオチド
WO2019193165A1 (en) 2018-04-05 2019-10-10 F. Hoffmann-La Roche Ag Use of fubp1 inhibitors for treating hepatitis b virus infection
US11732262B2 (en) 2018-04-05 2023-08-22 Hoffmann—La Roche, Inc. Use of FUBP1 inhibitors for treating hepatitis B virus infection
WO2019215065A1 (en) 2018-05-07 2019-11-14 Roche Innovation Center Copenhagen A/S Massively parallel discovery methods for oligonucleotide therapeutics
WO2019217459A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
WO2019215067A1 (en) 2018-05-07 2019-11-14 Roche Innovation Center Copenhagen A/S Massively parallel discovery methods for oligonucleotide therapeutics
WO2019215066A1 (en) 2018-05-07 2019-11-14 Roche Innovation Center Copenhagen A/S Quality control of lna oligonucleotide therapeutics using massively parallel sequencing
WO2019215175A1 (en) 2018-05-08 2019-11-14 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating myh7 expression
WO2019219723A1 (en) 2018-05-18 2019-11-21 F. Hoffmann-La Roche Ag Pharmaceutical compositions for treatment of microrna related diseases
WO2019224172A1 (en) 2018-05-25 2019-11-28 Roche Innovation Center Copenhagen A/S Novel process for making allofuranose from glucofuranose
WO2019233922A1 (en) 2018-06-05 2019-12-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
WO2019233921A1 (en) 2018-06-05 2019-12-12 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
US11066669B2 (en) 2018-06-05 2021-07-20 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
WO2019246112A1 (en) 2018-06-18 2019-12-26 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
WO2019243391A1 (en) 2018-06-21 2019-12-26 F. Hoffmann-La Roche Ag Hybridizing all-lna oligonucleotides
WO2019246262A2 (en) 2018-06-21 2019-12-26 University Of Rochester Methods of treating or inhibiting onset of huntington's disease
WO2020007772A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
WO2020007700A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting spi1
WO2020007702A1 (en) 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting bcl2l11
US11279929B2 (en) 2018-07-03 2022-03-22 Hoffmann-La Roche, Inc. Oligonucleotides for modulating Tau expression
WO2020007892A1 (en) 2018-07-03 2020-01-09 F. Hoffmann-La Roche Ag Oligonucleotides for modulating tau expression
US11753640B2 (en) 2018-07-03 2023-09-12 Hoffmann-La Roche Inc. Oligonucleotides for modulating Tau expression
WO2020007889A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting stat1
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011653A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011743A1 (en) 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mafb
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
WO2020011869A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting tlr2
WO2020011902A1 (en) 2018-07-13 2020-01-16 F. Hoffmann-La Roche Ag Oligonucleotides for modulating rtel1 expression
WO2020025563A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
WO2020025527A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
US11273442B1 (en) 2018-08-01 2022-03-15 Mammoth Biosciences, Inc. Programmable nuclease compositions and methods of use thereof
US11761029B2 (en) 2018-08-01 2023-09-19 Mammoth Biosciences, Inc. Programmable nuclease compositions and methods of use thereof
WO2020038976A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting usp8
WO2020038971A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting vcan
WO2020038973A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting sptlc1
WO2020038968A1 (en) 2018-08-23 2020-02-27 Roche Innovation Center Copenhagen A/S Microrna-134 biomarker
WO2020043750A1 (en) 2018-08-28 2020-03-05 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
EP3620519A1 (en) 2018-09-04 2020-03-11 F. Hoffmann-La Roche AG Use of isolated milk extracellular vesicles for delivering oligonucleotides orally
WO2020056341A2 (en) 2018-09-14 2020-03-19 Northwestern University Programming protein polymerization with dna
WO2020069055A1 (en) 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2020086701A1 (en) 2018-10-24 2020-04-30 Codiak Biosciences, Inc. Methods to improve potency of electroporation
WO2020089260A1 (en) 2018-11-01 2020-05-07 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting tia1
WO2020099533A1 (en) 2018-11-16 2020-05-22 F. Hoffmann-La Roche Ag Streptavidin-coated solid phases with a member of a binding pair
WO2020104492A1 (en) 2018-11-22 2020-05-28 Roche Innovation Center Copenhagen A/S Pyridinium salts as activators in the synthesis of stereodefined oligonucleotides
WO2020109344A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Occular administration device for antisense oligonucleotides
WO2020109343A1 (en) 2018-11-29 2020-06-04 F. Hoffmann-La Roche Ag Combination therapy for treatment of macular degeneration
WO2020118259A1 (en) 2018-12-06 2020-06-11 Northwestern University Protein crystal engineering through dna hybridization interactions
WO2020123663A1 (en) 2018-12-11 2020-06-18 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
WO2020136125A2 (en) 2018-12-21 2020-07-02 Boehringer Ingelheim International Gmbh Antisense oligonucleotides targeting card9
US11174470B2 (en) 2019-01-04 2021-11-16 Mammoth Biosciences, Inc. Programmable nuclease improvements and compositions and methods for nucleic acid amplification and detection
WO2020152303A1 (en) 2019-01-25 2020-07-30 F. Hoffmann-La Roche Ag Lipid vesicle for oral drug delivery
WO2020167822A2 (en) 2019-02-13 2020-08-20 University Of Rochester Gene networks that mediate remyelination of the human brain
WO2020169695A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Phosphonoacetate gapmer oligonucleotides
WO2020169696A1 (en) 2019-02-20 2020-08-27 Roche Innovation Center Copenhagen A/S Novel phosphoramidites
WO2020173845A1 (en) 2019-02-26 2020-09-03 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
US11279932B2 (en) 2019-02-27 2022-03-22 Ionis Pharmaceuticals, Inc. Modulators of MALAT1 expression
WO2020178258A1 (en) 2019-03-05 2020-09-10 F. Hoffmann-La Roche Ag Intracellular targeting of molecules
EP4219700A1 (en) 2019-03-07 2023-08-02 The Regents of the University of California Crispr-cas effector polypeptides and methods of use thereof
DE212020000516U1 (de) 2019-03-07 2022-01-17 The Regents of the University of California CRISPR-CAS-Effektorpolypeptide
WO2020186059A2 (en) 2019-03-12 2020-09-17 Crispr Therapeutics Ag Novel high fidelity rna-programmable endonuclease systems and uses thereof
WO2020191377A1 (en) 2019-03-21 2020-09-24 Codiak Biosciences, Inc. Extracellular vesicle conjugates and uses thereof
WO2020203880A1 (ja) 2019-03-29 2020-10-08 田辺三菱製薬株式会社 Ｄｕｘ４の発現を調節するための化合物、方法及び医薬組成物
US11261446B2 (en) 2019-03-29 2022-03-01 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating UBE3A-ATS
WO2020206115A2 (en) 2019-04-03 2020-10-08 Bristol-Myers Squibb Company Angptl2 antisense oligonucleotides and uses thereof
WO2020201339A1 (en) 2019-04-04 2020-10-08 F. Hoffmann-La Roche Ag Oligonucleotides for modulating atxn2 expression
US11286485B2 (en) 2019-04-04 2022-03-29 Hoffmann-La Roche Inc. Oligonucleotides for modulating ATXN2 expression
WO2020212301A1 (en) 2019-04-16 2020-10-22 Roche Innovation Center Copenhagen A/S Novel process for preparing nucleotide p(v) monomers
WO2020221705A1 (en) 2019-04-30 2020-11-05 Roche Innovation Center Copenhagen A/S Novel process for preparing rhenium chelated mag3 oligonucleotides
WO2020236600A1 (en) 2019-05-17 2020-11-26 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
WO2020243644A1 (en) 2019-05-31 2020-12-03 Streck, Inc. Detection of antibiotic resistance genes
WO2020245233A1 (en) 2019-06-06 2020-12-10 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2020245377A1 (en) 2019-06-07 2020-12-10 F. Hoffmann-La Roche Ag Hybridizing all-lna oligonucleotides
WO2021011936A2 (en) 2019-07-18 2021-01-21 University Of Rochester Cell-type selective immunoprotection of cells
WO2021020412A1 (ja) 2019-07-30 2021-02-04 塩野義製薬株式会社 Ｍｕｒｆ１を標的とする核酸医薬
WO2021030769A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with nras antisense oligonucleotides
WO2021030777A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle linked to molecules and uses thereof
WO2021030780A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting cebp/beta
WO2021030776A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting stat6
WO2021030773A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
WO2021030781A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with antisense oligonucleotides targeting kras
WO2021030768A1 (en) 2019-08-14 2021-02-18 Codiak Biosciences, Inc. Extracellular vesicles with stat3-antisense oligonucleotides
WO2021062058A1 (en) 2019-09-25 2021-04-01 Codiak Biosciences, Inc. Sting agonist comprising exosomes for treating neuroimmunological disorders
WO2021075538A1 (ja) 2019-10-18 2021-04-22 第一三共株式会社 二環性ホスホロアミダイトの製造方法
KR20220083707A (ko) 2019-10-18 2022-06-20 다이이찌 산쿄 가부시키가이샤 2 고리성 포스포르아미다이트의 제조 방법
WO2021092371A2 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
WO2021092145A1 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2021108647A1 (en) 2019-11-27 2021-06-03 Crispr Therapeutics Ag Methods of synthesizing rna molecules
WO2021119275A1 (en) 2019-12-11 2021-06-17 Intellia Therapeutics, Inc. Modified guide rnas for gene editing
WO2021123074A1 (en) 2019-12-18 2021-06-24 F. Hoffmann-La Roche Ag Methods of sequencing by synthesis using a consecutive labeling scheme
WO2021122993A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of saraf inhibitors for treating hepatitis b virus infection
WO2021122869A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of scamp3 inhibitors for treating hepatitis b virus infection
WO2021122735A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sept9 inhibitors for treating hepatitis b virus infection
WO2021122921A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of cops3 inhibitors for treating hepatitis b virus infection
WO2021122910A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of sbds inhibitors for treating hepatitis b virus infection
WO2021123086A1 (en) 2019-12-20 2021-06-24 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for inhibiting scn9a expression
WO2021130266A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of a therapeutic oligonucleotide targeting hbv and a tlr7 agonist for treatment of hbv
WO2021130270A1 (en) 2019-12-24 2021-07-01 F. Hoffmann-La Roche Ag Pharmaceutical combination of antiviral agents targeting hbv and/or an immune modulator for treatment of hbv
WO2021158810A1 (en) 2020-02-05 2021-08-12 Bristol-Myers Squibb Company Oligonucleotides for splice modulation of camk2d
WO2021170697A1 (en) 2020-02-28 2021-09-02 F. Hoffmann-La Roche Ag Oligonucleotides for modulating cd73 exon 7 splicing
WO2021184021A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting pmp22
WO2021184020A1 (en) 2020-03-13 2021-09-16 Codiak Biosciences, Inc. Methods of treating neuroinflammation
WO2021198883A1 (en) 2020-03-31 2021-10-07 Janssen Biopharma, Inc. Synthesis of oligonucleotides and related compounds
WO2021231204A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component 4 inhibitors for treating neurological diseases, and related compositons, systems and methods of using same
WO2021231210A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1r inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021231211A1 (en) 2020-05-11 2021-11-18 Genentech, Inc. Complement component c1s inhibitors for treating a neurological disease, and related compositions, systems and methods of using same
WO2021230286A1 (ja) 2020-05-12 2021-11-18 田辺三菱製薬株式会社 Ａｔａｘｉｎ ３発現を調節するための化合物、方法及び医薬組成物
WO2021229036A1 (en) 2020-05-13 2021-11-18 F. Hoffmann-La Roche Ag Oligonucleotide agonists targeting progranulin
WO2021233551A1 (en) 2020-05-22 2021-11-25 F.Hoffmann-La Roche Ag Oligonucleotides for splice modulation of card9
WO2021249993A1 (en) 2020-06-09 2021-12-16 Roche Innovation Center Copenhagen A/S Guanosine analogues for use in therapeutic polynucleotides
WO2021260197A1 (en) 2020-06-26 2021-12-30 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for modulating fubp1 expression
WO2022011214A1 (en) 2020-07-10 2022-01-13 Alnylam Pharmaceuticals, Inc. Circular sirnas
WO2022008935A1 (en) 2020-07-10 2022-01-13 Horizon Discovery Limited Method for producing genetically modified cells
WO2022018155A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Lna oligonucleotides for splice modulation of stmn2
WO2022018187A1 (en) 2020-07-23 2022-01-27 F. Hoffmann-La Roche Ag Oligonucleotides targeting rna binding protein sites
WO2022038211A2 (en) 2020-08-21 2022-02-24 F. Hoffmann-La Roche Ag Use of a1cf inhibitors for treating hepatitis b virus infection
WO2022076596A1 (en) 2020-10-06 2022-04-14 Codiak Biosciences, Inc. Extracellular vesicle-aso constructs targeting stat6
US11447521B2 (en) 2020-11-18 2022-09-20 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
WO2022107025A1 (en) 2020-11-18 2022-05-27 Lemba Bv Umlilo antisense transcription inhibitors
WO2022117747A2 (en) 2020-12-03 2022-06-09 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2022117745A1 (en) 2020-12-03 2022-06-09 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting atxn3
WO2022122613A1 (en) 2020-12-08 2022-06-16 F. Hoffmann-La Roche Ag Novel synthesis of phosphorodithioate oligonucleotides
WO2022129320A1 (en) 2020-12-18 2022-06-23 F. Hoffmann-La Roche Ag Antisense oligonucleotides for targeting progranulin
WO2022136140A1 (en) 2020-12-22 2022-06-30 F. Hoffmann-La Roche Ag Oligonucleotides targeting xbp1
WO2022147214A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2022147223A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
WO2022167456A1 (en) 2021-02-02 2022-08-11 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for inhibiting rtel1 expression
US11898145B2 (en) 2021-02-02 2024-02-13 Hoffmann-La Roche Inc. Enhanced oligonucleotides for inhibiting RTEL1 expression
WO2022178180A1 (en) 2021-02-17 2022-08-25 Codiak Biosciences, Inc. Extracellular vesicle linked to a biologically active molecule via an optimized linker and an anchoring moiety
WO2022178149A2 (en) 2021-02-17 2022-08-25 Codiak Biosciences, Inc. Extracellular vesicle-nlrp3 antagonist
WO2022192038A1 (en) 2021-03-12 2022-09-15 Northwestern University Antiviral vaccines using spherical nucleic acids
WO2022213118A1 (en) 2021-03-31 2022-10-06 Entrada Therapeutics, Inc. Cyclic cell penetrating peptides
WO2022212884A1 (en) 2021-04-01 2022-10-06 Codiak Biosciences, Inc. Extracellular vesicle compositions
WO2022240760A2 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING
WO2022241408A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating tissue distribution of intracellular therapeutics
WO2022240721A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity
WO2022256597A1 (en) 2021-06-04 2022-12-08 Translate Bio, Inc. Assay for quantitative assessment of mrna capping efficiency
WO2022258555A1 (en) 2021-06-08 2022-12-15 F. Hoffmann-La Roche Ag Oligonucleotide progranulin agonists
WO2022261292A1 (en) 2021-06-10 2022-12-15 Intellia Therapeutics, Inc. Modified guide rnas comprising an internal linker for gene editing
WO2022258753A1 (en) 2021-06-11 2022-12-15 Bayer Aktiengesellschaft Type v rna programmable endonuclease systems
EP4101928A1 (en) 2021-06-11 2022-12-14 Bayer AG Type v rna programmable endonuclease systems
WO2022271818A1 (en) 2021-06-23 2022-12-29 Entrada Therapeutics, Inc. Antisense compounds and methods for targeting cug repeats
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
WO2023003922A1 (en) 2021-07-21 2023-01-26 Alnylam Pharmaceuticals, Inc. Metabolic disorder-associated target gene irna compositions and methods of use thereof
WO2023021046A1 (en) 2021-08-16 2023-02-23 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
WO2023034817A1 (en) 2021-09-01 2023-03-09 Entrada Therapeutics, Inc. Compounds and methods for skipping exon 44 in duchenne muscular dystrophy
EP4144841A1 (en) 2021-09-07 2023-03-08 Bayer AG Novel small rna programmable endonuclease systems with impoved pam specificity and uses thereof
WO2023036669A1 (en) 2021-09-07 2023-03-16 Bayer Aktiengesellschaft Novel small rna programmable endonuclease systems with impoved pam specificity and uses thereof
WO2023043280A1 (ko) 2021-09-17 2023-03-23 주식회사 씨젠 합성 비자연 염기를 포함하는 태그 올리고뉴클레오타이드를 이용한 타겟 핵산 서열의 검출
WO2023052317A1 (en) 2021-09-29 2023-04-06 F. Hoffmann-La Roche Ag Rna editing
WO2023064530A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
WO2023078883A1 (en) 2021-11-03 2023-05-11 F. Hoffmann-La Roche Ag Oligonucleotides for modulating apolipoprotein e4 expression
WO2023083906A2 (en) 2021-11-11 2023-05-19 F. Hoffmann-La Roche Ag Pharmaceutical combinations for treatment of hbv
WO2023104693A1 (en) 2021-12-07 2023-06-15 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b
WO2023111336A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Oligonucleotide gba agonists
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
WO2023117738A1 (en) 2021-12-20 2023-06-29 F. Hoffmann-La Roche Ag Threose nucleic acid antisense oligonucleotides and methods thereof
WO2023122762A1 (en) 2021-12-22 2023-06-29 Camp4 Therapeutics Corporation Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2023118068A1 (en) 2021-12-23 2023-06-29 Bayer Aktiengesellschaft Novel small type v rna programmable endonuclease systems
WO2023141507A1 (en) 2022-01-20 2023-07-27 Genentech, Inc. Antisense oligonucleotides for modulating tmem106b expression
WO2023150553A1 (en) 2022-02-01 2023-08-10 University Of Rochester Gpr17 promoter-based targeting and transduction of glial progenitor cells
WO2023156652A1 (en) 2022-02-21 2023-08-24 F. Hoffmann-La Roche Ag Antisense oligonucleotide
WO2023217890A1 (en) 2022-05-10 2023-11-16 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting cfp-elk1 intergene region
WO2023220744A2 (en) 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2023222858A1 (en) 2022-05-18 2023-11-23 F. Hoffmann-La Roche Ag Improved oligonucleotides targeting rna binding protein sites
WO2023237587A1 (en) 2022-06-10 2023-12-14 Bayer Aktiengesellschaft Novel small type v rna programmable endonuclease systems
WO2023240277A2 (en) 2022-06-10 2023-12-14 Camp4 Therapeutics Corporation Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas
WO2023242324A1 (en) 2022-06-17 2023-12-21 F. Hoffmann-La Roche Ag Antisense oligonucleotides for targeting progranulin
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
WO2024046937A1 (en) 2022-08-29 2024-03-07 F. Hoffmann-La Roche Ag Threose nucleic acid antisense oligonucleotides and methods thereof
EP4332221A1 (en) 2022-08-29 2024-03-06 Roche Innovation Center Copenhagen A/S Threose nucleic acid antisense oligonucleotides and methods thereof
WO2024052403A1 (en) 2022-09-06 2024-03-14 F. Hoffmann-La Roche Ag Double-stranded rna molecule for administration to the eye
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
WO2024073042A1 (en) 2022-09-30 2024-04-04 Entrada Therapeutics, Inc. Ocular delivery of therapeutic agents
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
WO2024104914A1 (en) 2022-11-14 2024-05-23 BioNTech SE Rna capping efficiency assay
WO2024119145A1 (en) 2022-12-01 2024-06-06 Camp4 Therapeutics Corporation Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas
WO2024126654A1 (en) 2022-12-14 2024-06-20 F. Hoffmann-La Roche Ag Antisense oligonucleotides targeting actl6b

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