JP6026482B2 - 腫瘍抑制遺伝子に対する天然アンチセンス転写物の抑制による腫瘍抑制遺伝子関連疾患の治療 - Google Patents
腫瘍抑制遺伝子に対する天然アンチセンス転写物の抑制による腫瘍抑制遺伝子関連疾患の治療 Download PDFInfo
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Description
本出願は、その出願が参照によりその全体が本明細書に組み込まれる2008年12月4日出願米国仮特許出願第61/119,973号、2009年3月4日出願米国仮特許出願第61/157,249号、2009年4月3日出願米国仮特許出願第61/166,381号および2009年2月23日出願米国仮特許出願第61/154,594号の優先権を主張する。
本明細書において使用される専門用語は、特定の実施形態を記載する目的のためだけであり、本発明の限定となることを意図しない。本明細書において使用される単数形「a」、「an」および「the」は、文脈がそうでないと明確に示さなければ複数形を同様に含んで意味する。さらに用語「含んでいる(including)」、「含む(include)」、「有している(having)」、「有する(has)」、「有する(with)」またはそれらの変形は、詳細な記載および/または特許請求の範囲のいずれにおいても使用され、そのような用語は用語「含む(comprising)」と同様の様式で包括的であることを意図する。
標的:一実施形態において標的は、限定することなく、腫瘍抑制遺伝子に関連するセンスおよび/またはアンチセンスの非コードおよび/またはコード配列を含めた、腫瘍抑制遺伝子の核酸配列を含む。
重鎖形成領域)は、ワトソン-クリック様に塩基対形成する相補的RNA鎖である。
飾は、De Mesmaekerら、(1995) Acc. Chem. Res.、28:366〜374に見出すことができる。
外来性核酸の宿主細胞または生体への輸送は、細胞中または生体中の核酸を直接検出するステップによって評価されうる。そのような検出は、当技術分野において周知のいくつかの方法によって達成されうる。例えば、外来性核酸の存在は、サザンブロットまたは核酸に関連するヌクレオチド配列を特異的に増幅するプライマーを使用するポリメラーゼ連鎖反応(PCR)技術によって検出されうる。外来性核酸の発現も遺伝子発現分析を含む従来法を使用して測定されうる。例えば外来性核酸から産生されるmRNAはノーザンブロットおよび逆転写PCR(RT-PCR)を使用して検出および定量されうる。
本発明の化合物は、診断、治療および予防のためにならびに研究用試薬およびキットの構成要素として利用されうる。さらに、精緻な特異性を有して遺伝子発現を抑制できるアンチセンスオリゴヌクレオチドは、当業者によって特定の遺伝子の機能を解明するため、または生物学的経路の種々のメンバー間の機能を区別するためにしばしば使用される。
本発明のオリゴヌクレオチドの他の修飾は、オリゴヌクレオチドの活性、細胞分布または細胞への取り込みを増強する1つまたは複数の成分または複合体のオリゴヌクレオチドへの化学的連結を含む。これらの成分または複合体は、1級または2級ヒドロキシル基などの官能基に共有結合した複合基を含みうる。本発明の複合基は、干渉物質、腫瘍抑制分子、ポリアミン、ポリアミド、ポリエチレングリコール、ポリエーテル、オリゴマーの薬力学特性を増強する基、およびオリゴマーの薬物動態特性を増強する基を含む。典型的な複合基は、コレステロール、脂質、リン脂質、ビオチン、フェナジン、葉酸、フェナントリジン、アントラキノン、アクリジン、フルオレセイン、ローダミン、クマリン、および色素を含む。本発明の文脈において薬力学特性を増強する基は、取り込みを改善し、分解への耐性を増強し、および/または標的核酸との配列特異的ハイブリダイゼーションを強化する基を含む。本発明の文脈において薬物動態特性を増強する基は、本発明の化合物の取り込み、分布、代謝または排出を改善する基を含む。代表的複合基は、参照により本明細書に組み込まれる1992年10月23日出願の国際特許出願PCT/US92/09196および米国特許第6,287,860号において開示されている。複合体成分は、これだけに限らないがコレステロール成分、コール酸、チオエーテル、例えばヘキシル-S-トリチルチオール、チオコレステロール、脂肪族鎖、例えばドデカンジオールまたはウンデシル残基、リン脂質、例えばジ-ヘキサデシル-rac-グリセロールまたはトリエチルアンモニウム1,2-ジ-O-ヘキサデシル-rac-グリセロ-3-H-ホスホネート、ポリアミンまたはポリエチレングリコール鎖、あるいはアダマンタン酢酸、パルミチル成分、またはオクタデシルアミンもしくはヘキシルアミノ-カルボニル-オキシコレステロール成分などの脂質成分を含む。本発明のオリゴヌクレオチドは、活性原薬、例えばアスピリン、ワルファリン、フェニルブタゾン、イブプロフェン、スプロフェン、フェンブフェン、ケトプロフェン、(S)-(+)-プラノプロフェン、カプロフェン、ダンシルサルコシン、2,3,5-トリヨード安息香酸、フルフェナム酸、フォリン酸、ベンゾチアジアジド、クロロチアジド、ジアセピン、インドメチシン、バルビツール酸、セ
ファロスポリン、サルファ剤、抗糖尿病薬、抗菌剤または抗生物質とも複合体化されうる。
本発明の化合物は、取り込み、分布および/または吸収の補助ために、例えばリポソーム、受容体-標的分子、経口、直腸、局所または他の製剤として、他の分子、分子構造または化合物と、混合物と混合、封入、複合体化または他の方法で付随されうる。そのような取り込み、分布および/または吸収を補助する製剤の調製を説明する代表的米国特許は、これだけに限らないが、それぞれが本明細書に参照として組み込まれる米国特許5,108,921;5,354,844;5,416,016;5,459,127;5,521,291;5,543,165;5,547,932;5,583,020;5,591,721;4,426,330;4,534,899;5,013,556;5,108,921;5,213,804;5,227,170;5,264,221;5,356,633;5,395,619;5,416,016;5,417,978;5,462,854;5,469,854;5,512,295;5,527,528;5,534,259;5,543,152;5,556,948;5,580,575;および5,595,756を含む。
は、一緒にまたは連続的に使用されうる。
治療用組成物の処方およびそれらの続く投与(投薬)は、当業者の技能の範囲内であると考えられる。投薬は、数日間から数カ月間続くまたは治療が効果的になるもしくは病態の減退が達成されるまでの治療過程において、治療される病態の重症度および応答性に依存する。最適な投薬計画は、患者身体での薬剤蓄積の測定から算出されうる。当業者は、最適投与量、投薬方法および繰り返し率(repetition rate)を容易に決定できる。最適な投与量は、個々のオリゴヌクレオチドの相対的効力に応じて変動する場合があり、一般にin vitroおよびin vivo動物モデルにおいて効果的であると見出されたEC50に基づいて概算されうる。一般に投与量は、体重1kgあたり0.01μg〜100gであり、1日に、1週間に、1カ月にもしくは1年に1回もしくは複数回またはさらに4〜30年ごとに1回である場合がある。当業者は、測定された滞留時間および体液または組織における薬剤の濃度に基づいて投薬についての繰り返し率を容易に概算できる。治療の成功に続いて、病態の再発を予防するために患者に維持療法を受けさせることが望ましい場合があり、ここでオリゴヌクレオチドは維持投与において体重1kgあたり0.01μg〜100g、1日1回または複数回から20年ごとに1回の範囲で投与される。
以下の非限定的実施例は、本発明の選択された実施形態を例示するために利用できる。示される構成要素の割合における変動および構成要素における代替は当業者に明らかであり、本発明の実施形態の範囲内であることは理解される。
腫瘍抑制遺伝子ポリヌクレオチドのアンチセンス鎖および/またはセンス鎖核酸分子に特異的なアンチセンスオリゴヌクレオチドの設計
上に示すとおり用語「に特異的なオリゴヌクレオチド」または「オリゴヌクレオチド標的」は、(i)標的遺伝子の一部分と安定な複合体を形成できる配列、または(ii)標的遺伝子のmRNA転写物の一部分と安定な2重鎖を形成できる配列を有するオリゴヌクレオチドを意味する。
腫瘍抑制遺伝子オリゴヌクレオチド遺伝子発現の調節
アンチセンスオリゴヌクレオチドでのHepG2細胞の処置
ATCC (cat# HB-8065)由来のHepG2細胞を増殖培地(MEM/EBSS (Hyclone cat #SH30024またはMediatech cat # MT-10-010-CV) +10% FBS (Mediatech cat# MT35-011-CV)+ペニシリン/ストレプトマイシン(Mediatech cat# MT30-002-CI))中、37℃、5% CO2で増殖させた。実験前日に、細胞を1mlあたり1.5×105個の密度で6ウエルプレートに再播種し、37℃、5% CO2でインキュベートした。実験当日に6ウエルプレートの培地を新鮮増殖培地に交換した。全てのアンチセンスオリゴヌクレオチドを濃度20μMに希釈した。この溶液2μlをOpti-MEM培地(Gibco cat#31985-070) 400μlおよびLipofectamine 2000 (Invitrogen cat# 11668019) 4μlと室温で20分間インキュベートし、HepG2細胞を含む6ウエルプレートの各ウエルに添加した。オリゴヌクレオチド溶液の代わりに水2μlを含む同様の混合物を偽形質移入対照用に使用した。37℃、5% CO2での3〜18時間のインキュベーション後、培地を新鮮増殖培地に交換した。アンチセンスオリゴヌクレオチドの添加の48時間後、培地を除去し、RNAを細胞からPromegaからのSV Total RNA Isolation System (cat # Z3105)またはQiagenからのRNeasy Total RNA Isolation kit (cat# 74181)を製造者の手順書に従って使用して抽出した。RNA 600ngをThermo ScientificからのVerso cDNAキット(cat#AB1453B)またはHigh Capacity cDNA Reverse Transcriptionキット(cat#4368813)を製造者の手順書に記載のとおり使用して実施した逆転写反応に加えた。この逆転写反応からのcDNAをABI Taqman gene Expression Mix (cat#4369510)およびABIによって設計されたプライマー/プローブを使用するリアルタイムPCRによって遺伝子発現をモニターするために使用した。以下のPCRサイクルを使用した: 50℃で2分間、95℃で10分間、(95℃で15秒間、60℃で1分間)を40サイクル、StepOne Plus Real Time PCR Machine (Applied Biosystems Inc.またはMx4000 thermal cycler (Stratagene)を使用。
使用したp73 Expression Assays(ABI cat#)、全てのプローブはMGBを伴う。
p73:Hs00232088_m1(標的配列ACCTCTGGAGCTCTCTGGAAC、エクソン2、配列番号41)。
p73as:Hs00215135_m1(標的配列TATGATGGAAAGGTGCGCATCCTTA、エクソン7、配列番号42)およびHs00892470_g1
リアルタイムPCR結果は、HepG2細胞中の腫瘍抑制遺伝子mRNAのレベルが、腫瘍抑制遺伝子に対して設計されたsiRNAのうちの2つ(腫瘍抑制遺伝子_1、P=0.02および腫瘍抑制遺伝子_2、P=0.04、図1A)での処置の48時間後に有意に増大することを示す。同じ試料において腫瘍抑制遺伝子RNAのレベルは腫瘍抑制遺伝子へのsiRNAでの処置後に低下している可能性がある(図1B)。
ATCC(cat#CRL-1715)由来のTM4細胞を増殖培地(MEM/EBSS (Hyclone cat#SH30024またはMediatech cat#MT-10-010-CV) +10% FBS (Mediatech cat#MT35-OH-CV)+ペニシリン/ストレプトマイシン(Mediatech cat#MT30-002-CI))中、37℃、5% CO2で増殖させた。実験前日に、細胞を1mlあたり1.5×105個の密度で6ウエルプレートに再播種し、37℃、5% CO2でインキュベートした。実験当日に6ウエルプレートの培地を新鮮増殖培地に交換した。全てのアンチセンスオリゴヌクレオチドを濃度20μMに希釈した。この溶液2μlをOpti-MEM培地(Gibco cat#31985-070)400μlおよびLipofectamine 2000(Invitrogen cat#11668019)4μlと室温で20分間インキュベートし、TM4細胞を含む6ウエルプレートの各ウエルに添加した。オリゴヌクレオチド溶液の代わりに水2μlを含む同様の混合物を偽形質移入対照用に使用した。37℃、5% CO2での3〜18時間のインキュベーション後、培地を新鮮増殖培地に交換した。アンチセンスオリゴヌクレオチドの添加の48時間後、培地を除去し、RNAを細胞からPromegaからのSV Total RNA Isolation System(cat#Z3105)またはQiagenからのRNeasy Total RNA Isolation kit(cat#74181)を製造者の手順書に従って使用して抽出した。RNA 600ngをThermo ScientificからのVerso cDNAキット(cat#AB1453B)またはHigh Capacity cDNA Reverse Transcription Kit(cat#4368813)を製造者の手順書に記載のとおり使用して実施した逆転写反応に加えた。この逆転写反応からのcDNAをABI Taqman gene Expression Mix (cat#4369510)およびABI (Applied Biosystems Taqman gene Expression Assay:Mm00660220_m1、Applied Biosystems Inc.、Foster City CA)によって設計されたプライマー/プローブを使用するリアルタイムPCRによって遺伝子発現をモニターするために使用した。以下のPCRサイクルを使用した:50℃で2分間、95℃で10分間、(95℃で15秒間、60℃で1分間)を40サイクル、StepOne Plus Real Time PCR Machine (Applied Biosystems)を使用。
リアルタイムPCR結果は、マウスTM4細胞中の腫瘍抑制遺伝子mRNAのレベルが、腫瘍抑制遺伝子アンチセンスHs.668503に対して設計されたオリゴの1つ、および腫瘍抑制遺伝子アンチセンスWDR8に対して設計されたオリゴの1つでの処置の48時間後に有意に増大することを示す(図1D)。
ATCC由来のHUVEC細胞(Promo Cell cat#C-12253)をEpithelial Growth Media(Promo Cell cat#C-22010)中、37℃、5% CO2で増殖させた。実験前日に、Promo Cell Detach Kit(cat#C-41200)を使用して細胞を1mlあたり1.5×105個の密度で6ウエルプレートに再播種し、37℃、5% CO2でインキュベートした。実験当日に6ウエルプレートの培地を新鮮Epithelial Growth Mediaに交換した。全てのアンチセンスオリゴヌクレオチドを濃度20μMに希釈した。この溶液2μlをOpti-MEM培地(Gibco cat#31985-070)400μlおよびLipofectamine 2000(Invitrogen cat#11668019)4μlと室温で20分間インキュベートし、HUVEC細胞を含む6ウエルプレートの各ウエルに添加した。オリゴヌクレオチド溶液の代わりに水2μlを含む同様の混合物を偽形質移入対照用に使用した。37℃、5% CO2での3〜18時間のインキュベーション後、培地を新鮮増殖培地に交換した。アンチセンスオリゴヌクレオチドの添加の48時間後、培地を除去し、RNAを細胞からPromegaからのSV Total RNA Isolation System(cat# Z3105)またはQiagenからのRNeasy Total RNA Isolation kit(cat#74181)を製造者の手順書に従って使用して抽出した。RNA 600ngをThermo ScientificからのVerso cDNAキット(cat#AB1453B)を製造者の手順書に記載のとおり使用して実施した逆転写反応に加えた。この逆転写反応からのcDNAをABI Taqman gene Expression Mix(cat#4369510)およびABI(Applied Biosystems Taqman Gene Expression Assays: Hs00153340_m1およびHs00216360_m1、Applied Biosystems Inc.、Foster City CA)によって設計されたプライマー/プローブを使用するリアルタイムPCRによって遺伝子発現をモニターするために使用した。以下のPCRサイクルを使用した:50℃で2分間、95℃で10分間、(95℃で15秒間、60℃で1分間)を40サイクル、StepOne Plus Real Time PCR Machine (Applied Biosystems Inc.)またはMx4000 thermal cycler(Stratagene)を使用。
使用したP53Expression Assays(ABI cat#)、全てのプローブはFAM/MGB:18S:4319413Eを伴う。
P53:Hs00153340_m1(標的配列CTTCCCTGGATTGGCAGCCAGACTG、配列番号43)
P53as:Hs00216360_m1(標的配列ATATGCAGAAATGGTCCCTGTCCTT、配列番号44)
リアルタイムPCR結果は、HUVEC細胞中のp53 mRNAのレベルが、p53asに対して設計された全てのsiRNAでの処置の48時間後に有意に増大することを示す(図2)。
Claims (30)
- in vivoまたはin vitroで患者の細胞または組織におけるPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御するための組成物であって、
PTENポリヌクレオチドの天然アンチセンスポリヌクレオチドに特異的にハイブリダイズし、配列番号36に少なくとも90%の配列同一性を有し、かつPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する活性を有する長さ27〜30ヌクレオチドの少なくとも1つのアンチセンスオリゴヌクレオチドを含む組成物。 - in vivoまたはin vitroで患者の細胞または組織における配列番号6を有するPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御するための組成物であって、
配列番号14または15を有するPTEN遺伝子の天然アンチセンスポリヌクレオチドに特異的にハイブリダイズし、配列番号36に少なくとも90%の配列同一性を有し、かつPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する活性を有する長さ27〜30ヌクレオチドのアンチセンスオリゴヌクレオチドを含む組成物。 - in vivoまたはin vitroで患者の細胞または組織における配列番号6を有するPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御するための組成物であって、配列番号14および15から選択されるPTEN腫瘍抑制遺伝子ポリヌクレオチドの天然アンチセンスポリヌクレオチドの領域を標的とし、配列番号36に少なくとも90%の配列同一性を有し、かつ前記天然アンチセンスポリヌクレオチドの領域に特異的にハイブリダイズし、かつPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する活性を有する、長さ27〜30ヌクレオチドの少なくとも1つのアンチセンスオリゴヌクレオチドを含む組成物。
- PTEN腫瘍抑制遺伝子ポリヌクレオチドの発現が対照と比較してin vivoまたはin vitroで増大する、請求項3に記載の組成物。
- 少なくとも1つのアンチセンスオリゴヌクレオチドが配列番号14を有するPTEN腫瘍抑制遺伝子ポリヌクレオチドの天然アンチセンス配列を標的にする、請求項3に記載の組成物。
- 少なくとも1つのアンチセンスオリゴヌクレオチドがPTEN腫瘍抑制遺伝子ポリヌクレオチドのコードおよび/または非コード核酸配列に対する天然アンチセンスポリヌクレオチドを標的にする、請求項3に記載の組成物。
- 少なくとも1つのアンチセンスオリゴヌクレオチドがPTEN腫瘍抑制遺伝子ポリヌクレオチドのオーバーラップおよび/または非オーバーラップ配列を有する天然アンチセンスポリヌクレオチドを標的にする、請求項3に記載の組成物。
- 少なくとも1つのアンチセンスオリゴヌクレオチドが、少なくとも1つの修飾された糖部分、少なくとも1つの修飾されたヌクレオシド間結合、少なくとも1つの修飾されたヌクレオチドおよびそれらの組み合わせから選択される1つまたは複数の修飾を含む、請求項3に記載の組成物。
- 1つまたは複数の修飾が2'-O-メトキシエチル修飾糖部分、2'-メトキシ修飾糖部分、2'-O-アルキル修飾糖部分、二環性糖部分およびそれらの組み合わせから選択される少なくとも1つの修飾された糖部分を含む、請求項8に記載の組成物。
- 1つまたは複数の修飾がホスホロチオエート、アルキルホスホネート、ホスホロジチオエート、アルキルホスホノチオエート、ホスホラミデート、カルバメート、カーボネート、リン酸トリエステル、アセトアミデート、カルボキシメチルエステルおよびそれらの組み合わせから選択される少なくとも1つの修飾されたヌクレオシド間結合を含む、請求項8に記載の組成物。
- 1つまたは複数の修飾が、ペプチド核酸(PNA)、ロックド核酸(LNA)、アラビノ核酸(FANA)、それらの類似体、誘導体および組み合わせから選択される少なくとも1つの修飾されたヌクレオチドを含む、請求項8に記載の組成物。
- 少なくとも1つのオリゴヌクレオチドが配列番号36に記載のオリゴヌクレオチド配列を含む、請求項1に記載の組成物。
- in vivoまたはin vitroで哺乳動物の細胞または組織における配列番号6を有するPTEN腫瘍抑制遺伝子の発現を上方制御するための組成物であって
配列番号14または15を有するPTEN腫瘍抑制遺伝子ポリヌクレオチドの天然アンチセンスポリヌクレオチドに特異的であり、配列番号36に少なくとも90%の配列同一性を有し、前記PTEN腫瘍抑制遺伝子ポリヌクレオチドの天然アンチセンスポリヌクレオチドに特異的にハイブリダイズし、かつin vivoまたはin vitroで哺乳動物の細胞または組織におけるPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する長さ27〜30ヌクレオチドの少なくとも1つの低分子干渉RNA(siRNA)オリゴヌクレオチドを含む組成物。 - 少なくとも1つの修飾を含む長さ27〜30ヌクレオチドの合成修飾オリゴヌクレオチドであって、少なくとも1つの修飾が、少なくとも1つの修飾された糖部分、少なくとも1つの修飾されたヌクレオチド間結合、少なくとも1つの修飾されたヌクレオチド、およびそれらの組み合わせから選択され、さらに、配列番号14または15を有する天然アンチセンスポリヌクレオチドにハイブリダイズし、配列番号36に少なくとも90%の配列同一性を有し、かつ正常対照と比較してin vivoまたはin vitroでPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御するアンチセンス化合物であるオリゴヌクレオチド。
- 少なくとも1つの修飾が、ホスホロチオエート、アルキルホスホネート、ホスホロジチオエート、アルキルホスホノチオエート、ホスホラミデート、カルバメート、カーボネート、リン酸トリエステル、アセトアミデート、カルボキシメチルエステルおよびそれらの組み合わせからなる群から選択されるヌクレオチド間結合を含む、請求項14に記載のオリゴヌクレオチド。
- 少なくとも1つのホスホロチオエートヌクレオチド間結合を含む、請求項14に記載のオリゴヌクレオチド。
- ホスホロチオエートヌクレオチド間結合の骨格を含む、請求項14に記載のオリゴヌクレオチド。
- ペプチド核酸、ロックド核酸(LNA)、それらの類似体、誘導体、および組み合わせから選択される少なくとも1つの修飾されたヌクレオチドを含む、請求項14に記載のオリゴヌクレオチド。
- ホスホロチオエート、アルキルホスホネート、ホスホロジチオエート、アルキルホスホノチオエート、ホスホラミデート、カルバメート、カーボネート、リン酸トリエステル、アセトアミデート、カルボキシメチルエステル、およびそれらの組み合わせから選択されるヌクレオチド間結合を含む複数の修飾を含む、請求項14に記載のオリゴヌクレオチド。
- ペプチド核酸、ロックド核酸(LNA)、それらの類似体、誘導体、および組み合わせから選択される修飾されたヌクレオチドを含む複数の修飾を含む、請求項14に記載のオリゴヌクレオチド。
- 2'-O-メトキシエチル修飾糖部分、2'-メトキシ修飾糖部分、2'-O-アルキル修飾糖部分、二環性糖部分、およびそれらの組み合わせから選択される少なくとも1つの修飾された糖部分を含む、請求項14に記載のオリゴヌクレオチド。
- 2'-O-メトキシエチル修飾糖部分、2'-メトキシ修飾糖部分、2'-O-アルキル修飾糖部分、二環性糖部分、およびそれらの組み合わせから選択される修飾された糖部分を含む複数の修飾を含む、請求項14に記載のオリゴヌクレオチド。
- 少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドにハイブリダイズし、かつ正常対照と比較してin vivoまたはin vitroで少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する、請求項14に記載のオリゴヌクレオチド。
- 配列番号36に記載の配列を含む、請求項14に記載のオリゴヌクレオチド。
- 請求項14に記載の1つまたは複数のオリゴヌクレオチドおよび医薬として許容可能な賦形剤を含む組成物。
- 1つまたは複数のオリゴヌクレオチドが、配列番号36に記載のヌクレオチド配列を含む、請求項25に記載の組成物。
- 配列番号36に記載のオリゴヌクレオチドが、1つまたは複数の修飾またはヌクレオチド置換を含む、請求項26に記載の組成物。
- 1つまたは複数の修飾が、ホスホロチオエート、メチルホスホネート、ペプチド核酸、ロックド核酸(LNA)分子およびそれらの組み合わせから選択される、請求項27に記載の組成物。
- 少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドおよび/または少なくとも1つのそのコード産物に関連する疾患を予防するまたは治療するための組成物であって、
少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドの天然アンチセンス配列に結合し、かつ前記少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドの発現を上方制御する少なくとも1つの請求項14に記載のオリゴヌクレオチドの治療有効量を含む組成物。 - 少なくとも1つのPTEN腫瘍抑制遺伝子ポリヌクレオチドに関連する疾患が、アポトーシスの減少または増加に関連する疾患、組織/細胞の老化、癌(表1に記載のものを含む)、自己免疫疾患、エイズを含めた免疫不全症、老化、神経変性疾患もしくは障害(例えば、アルツハイマー病、毛細血管拡張性運動失調症、パーキンソン病、筋萎縮性側索硬化症、ハンチントン病など)、過形成性疾患(例えば、ケロイド)、関節リウマチ、冠動脈心疾患、虚血性細胞死、リンパ球増殖性障害、アテローム性動脈硬化症、骨粗鬆症、骨髄異形成症候群、毒素による疾患、ウイルス感染症、創傷治癒、カウデン病(CD)、レルミット・デュクロ病(LDD)、バナヤン・ゾナナ症候群(BZS、バナヤン・ライリー・ルバルカバ症候群、ルバルカバ・ミーレ・スミス症候群およびライリー・スミス症候群としても公知である)、移植、アポトーシス関連疾患もしくは障害、代謝性の疾患もしくは状態(例えば、糖尿病)、腎臓の疾患もしくは障害、心筋梗塞/心不全、虚血、敗血症、特定の造血性炎症性細胞が過剰にある炎症性疾患、増殖性疾患、ならびにアポトーシスの増加による炎症性疾患を治療するための治療パラダイムがある疾患もしくは障害から選択される、請求項29に記載の組成物。
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Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2660523C (en) | 2006-08-11 | 2019-03-19 | Prosensa Technologies B.V. | Methods and means for treating dna repeat instability associated genetic disorders |
CA2745811C (en) | 2008-12-04 | 2021-07-13 | Joseph Collard | Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene |
MX2011005910A (es) | 2008-12-04 | 2011-06-17 | Opko Curna Llc | Tratamiento de enfermedades relacionadas con eritropoyetina (epo) mediante inhibicion del transcrito antisentido natural a eritropoyetina. |
DK2519632T3 (en) * | 2009-12-31 | 2018-07-23 | Curna Inc | TREATMENT OF INSULIN RECEPTOR SUBSTRATE 2- (IRS2) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPTION TO IRS2 AND TRANSCRIPTION FACTOR E3 (TFE3) |
DK2593547T3 (en) * | 2010-07-14 | 2018-02-26 | Curna Inc | Treatment of Discs large homolog (DLG) related diseases by inhibition of natural antisense transcript to DLG |
US9920317B2 (en) | 2010-11-12 | 2018-03-20 | The General Hospital Corporation | Polycomb-associated non-coding RNAs |
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 |
US8987225B2 (en) * | 2010-11-23 | 2015-03-24 | Curna, Inc. | Treatment of NANOG related diseases by inhibition of natural antisense transcript to NANOG |
TWI658830B (zh) | 2011-06-08 | 2019-05-11 | 日東電工股份有限公司 | Hsp47表現調控強化用類視色素脂質體 |
US10196637B2 (en) | 2011-06-08 | 2019-02-05 | Nitto Denko Corporation | Retinoid-lipid drug carrier |
ITMI20120275A1 (it) | 2012-02-24 | 2013-08-25 | Biogenera Societa A Responsabilita Limitata | Oligonucleotidi per la modulazione dell'espressione genica e loro usi |
RS56319B1 (sr) * | 2012-04-23 | 2017-12-29 | Biomarin Tech Bv | Oligonukleotidi koji moduliraju rnk sa poboljšanim karakteristikama za lečenje neuromišićnih poremećaja |
EP3511416A1 (en) | 2012-05-16 | 2019-07-17 | Translate Bio MA, Inc. | Compositions and methods for modulating gene expression |
CN104583402A (zh) | 2012-05-16 | 2015-04-29 | Rana医疗有限公司 | 用于调节mecp2表达的组合物和方法 |
US10059941B2 (en) | 2012-05-16 | 2018-08-28 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
SG11201407486PA (en) | 2012-05-16 | 2014-12-30 | Rana Therapeutics Inc | Compositions and methods for modulating utrn expression |
US10837014B2 (en) | 2012-05-16 | 2020-11-17 | Translate Bio Ma, Inc. | Compositions and methods for modulating SMN gene family expression |
US20150159161A1 (en) * | 2012-05-16 | 2015-06-11 | Rana Therapeutics, Inc. | Compositions and methods for modulating pten expression |
EP2850188A4 (en) | 2012-05-16 | 2016-01-20 | Rana Therapeutics Inc | COMPOSITIONS AND METHODS FOR MODULATING THE EXPRESSION OF THE MULTIGENIC FAMILY OF HEMOGLOBIN |
AU2013262699A1 (en) | 2012-05-16 | 2015-01-22 | Rana Therapeutics, Inc. | Compositions and methods for modulating ATP2A2 expression |
CA2921457A1 (en) * | 2013-08-16 | 2015-02-19 | Rana Therapeutics, Inc. | Heterochromatin forming non-coding rnas |
US11162096B2 (en) | 2013-10-14 | 2021-11-02 | Ionis Pharmaceuticals, Inc | Methods for modulating expression of C9ORF72 antisense transcript |
EP3058068B1 (en) * | 2013-10-14 | 2019-04-24 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
EP3212824A4 (en) | 2014-10-30 | 2018-08-08 | The General Hospital Corporation | Methods for modulating atrx-dependent gene repression |
US10793855B2 (en) | 2015-01-06 | 2020-10-06 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of C9ORF72 antisense transcript |
US10900036B2 (en) | 2015-03-17 | 2021-01-26 | The General Hospital Corporation | RNA interactome of polycomb repressive complex 1 (PRC1) |
WO2016167780A1 (en) | 2015-04-16 | 2016-10-20 | Ionis Pharmaceuticals, Inc. | Compositions for modulating expression of c9orf72 antisense transcript |
CN114224907A (zh) * | 2015-07-02 | 2022-03-25 | 希望之城 | 包括硫代磷酸化寡脱氧核苷酸的化合物和组合物及其使用方法 |
CA3042401A1 (en) | 2016-11-01 | 2018-05-11 | The Research Foundation For The State University Of New York | 5-halouracil-modified micrornas and their use in the treatment of cancer |
CN109022462B (zh) * | 2017-06-08 | 2021-12-21 | 中山大学附属第一医院 | 一种PTEN基因的上游开放阅读框31aa-uORF核苷酸及其编码的多肽的应用 |
CN112236131A (zh) | 2018-03-29 | 2021-01-15 | 技术研究及发展基金有限公司 | 包含pten抑制剂的囊泡及其用途 |
CN110184271A (zh) * | 2019-06-04 | 2019-08-30 | 遵义医科大学珠海校区 | 一种mRNA-like ncRNA、抑制其表达的反义RNA及两者的应用 |
RU2763992C1 (ru) * | 2020-10-08 | 2022-01-12 | федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр онкологии" Министерства здравоохранения Российской Федерации | Способ бесконтактной стимуляции транскрипционной активности гена ингибитора циклинзависимой киназы 2 в опухолевых клетках предстательной железы |
Family Cites Families (399)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US4426330A (en) | 1981-07-20 | 1984-01-17 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US4534899A (en) | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
JPS5927900A (ja) | 1982-08-09 | 1984-02-14 | Wakunaga Seiyaku Kk | 固定化オリゴヌクレオチド |
FR2540122B1 (fr) | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
US4605735A (en) | 1983-02-14 | 1986-08-12 | Wakunaga Seiyaku Kabushiki Kaisha | Oligonucleotide derivatives |
US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
NZ207394A (en) | 1983-03-08 | 1987-03-06 | Commw Serum Lab Commission | Detecting or determining sequence of amino acids |
US4824941A (en) | 1983-03-10 | 1989-04-25 | Julian Gordon | Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems |
US4587044A (en) | 1983-09-01 | 1986-05-06 | The Johns Hopkins University | Linkage of proteins to nucleic acids |
US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
US5430136A (en) | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
US5367066A (en) | 1984-10-16 | 1994-11-22 | Chiron Corporation | Oligonucleotides with selectably cleavable and/or abasic sites |
US5258506A (en) | 1984-10-16 | 1993-11-02 | Chiron Corporation | Photolabile reagents for incorporation into oligonucleotide chains |
US4828979A (en) | 1984-11-08 | 1989-05-09 | Life Technologies, Inc. | Nucleotide analogs for nucleic acid labeling and detection |
US4754065A (en) | 1984-12-18 | 1988-06-28 | Cetus Corporation | Precursor to nucleic acid probe |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4762779A (en) | 1985-06-13 | 1988-08-09 | Amgen Inc. | Compositions and methods for functionalizing nucleic acids |
US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
US5317098A (en) | 1986-03-17 | 1994-05-31 | Hiroaki Shizuya | Non-radioisotope tagging of fragments |
JPS638396A (ja) | 1986-06-30 | 1988-01-14 | Wakunaga Pharmaceut Co Ltd | ポリ標識化オリゴヌクレオチド誘導体 |
EP0260032B1 (en) | 1986-09-08 | 1994-01-26 | Ajinomoto Co., Inc. | Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers |
US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US4904582A (en) | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
ATE113059T1 (de) | 1987-06-24 | 1994-11-15 | Florey Howard Inst | Nukleosid-derivate. |
US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
US5525465A (en) | 1987-10-28 | 1996-06-11 | Howard Florey Institute Of Experimental Physiology And Medicine | Oligonucleotide-polyamide conjugates and methods of production and applications of the same |
DE3738460A1 (de) | 1987-11-12 | 1989-05-24 | Max Planck Gesellschaft | Modifizierte oligonukleotide |
EP0348458B1 (en) | 1987-11-30 | 1997-04-09 | University Of Iowa Research Foundation | Dna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes |
US5403711A (en) | 1987-11-30 | 1995-04-04 | University Of Iowa Research Foundation | Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved |
US5288512A (en) | 1987-12-15 | 1994-02-22 | The Procter & Gamble Company | Reduced calorie fats made from triglycerides containing medium and long chain fatty acids |
US5082830A (en) | 1988-02-26 | 1992-01-21 | Enzo Biochem, Inc. | End labeled nucleotide probe |
NL8800756A (nl) | 1988-03-25 | 1989-10-16 | Vereniging Voor Christelijk Wetenschappelijk Onderwijs | Genetisch gemanipuleerde plantecellen en planten, alsmede daarvoor bruikbaar recombinant dna. |
JPH03503894A (ja) | 1988-03-25 | 1991-08-29 | ユニバーシィティ オブ バージニア アランミ パテンツ ファウンデイション | オリゴヌクレオチド n‐アルキルホスホラミデート |
US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
US5109124A (en) | 1988-06-01 | 1992-04-28 | Biogen, Inc. | Nucleic acid probe linked to a label having a terminal cysteine |
US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
US5175273A (en) | 1988-07-01 | 1992-12-29 | Genentech, Inc. | Nucleic acid intercalating agents |
US5262536A (en) | 1988-09-15 | 1993-11-16 | E. I. Du Pont De Nemours And Company | Reagents for the preparation of 5'-tagged oligonucleotides |
US5512439A (en) | 1988-11-21 | 1996-04-30 | Dynal As | Oligonucleotide-linked magnetic particles and uses thereof |
US5457183A (en) | 1989-03-06 | 1995-10-10 | Board Of Regents, The University Of Texas System | Hydroxylated texaphyrins |
US5599923A (en) | 1989-03-06 | 1997-02-04 | Board Of Regents, University Of Tx | Texaphyrin metal complexes having improved functionalization |
US5354844A (en) | 1989-03-16 | 1994-10-11 | Boehringer Ingelheim International Gmbh | Protein-polycation conjugates |
US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
US5391723A (en) | 1989-05-31 | 1995-02-21 | Neorx Corporation | Oligonucleotide conjugates |
US5256775A (en) | 1989-06-05 | 1993-10-26 | Gilead Sciences, Inc. | Exonuclease-resistant oligonucleotides |
US4958013A (en) | 1989-06-06 | 1990-09-18 | Northwestern University | Cholesteryl modified oligonucleotides |
US5227170A (en) | 1989-06-22 | 1993-07-13 | Vestar, Inc. | Encapsulation process |
US6203976B1 (en) | 1989-07-18 | 2001-03-20 | Osi Pharmaceuticals, Inc. | Methods of preparing compositions comprising chemicals capable of transcriptional modulation |
US5451463A (en) | 1989-08-28 | 1995-09-19 | Clontech Laboratories, Inc. | Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
US5254469A (en) | 1989-09-12 | 1993-10-19 | Eastman Kodak Company | Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures |
US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
US5527528A (en) | 1989-10-20 | 1996-06-18 | Sequus Pharmaceuticals, Inc. | Solid-tumor treatment method |
US5356633A (en) | 1989-10-20 | 1994-10-18 | Liposome Technology, Inc. | Method of treatment of inflamed tissues |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
EP0942000B1 (en) | 1989-10-24 | 2004-06-23 | Isis Pharmaceuticals, Inc. | 2'-Modified oligonucleotides |
US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
US5292873A (en) | 1989-11-29 | 1994-03-08 | The Research Foundation Of State University Of New York | Nucleic acids labeled with naphthoquinone probe |
US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
US5457189A (en) | 1989-12-04 | 1995-10-10 | Isis Pharmaceuticals | Antisense oligonucleotide inhibition of papillomavirus |
US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
US5580575A (en) | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5469854A (en) | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
US5486603A (en) | 1990-01-08 | 1996-01-23 | Gilead Sciences, Inc. | Oligonucleotide having enhanced binding affinity |
US5623065A (en) | 1990-08-13 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Gapped 2' modified oligonucleotides |
US5587470A (en) | 1990-01-11 | 1996-12-24 | Isis Pharmaceuticals, Inc. | 3-deazapurines |
US5852188A (en) | 1990-01-11 | 1998-12-22 | Isis Pharmaceuticals, Inc. | Oligonucleotides having chiral phosphorus linkages |
US5578718A (en) | 1990-01-11 | 1996-11-26 | Isis Pharmaceuticals, Inc. | Thiol-derivatized nucleosides |
US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
US5220007A (en) | 1990-02-15 | 1993-06-15 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of RNA and production of encoded polypeptides |
US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
AU7579991A (en) | 1990-02-20 | 1991-09-18 | Gilead Sciences, Inc. | Pseudonucleosides and pseudonucleotides and their polymers |
US5214136A (en) | 1990-02-20 | 1993-05-25 | Gilead Sciences, Inc. | Anthraquinone-derivatives oligonucleotides |
US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
US6034233A (en) | 1990-05-04 | 2000-03-07 | Isis Pharmaceuticals Inc. | 2'-O-alkylated oligoribonucleotides and phosphorothioate analogs complementary to portions of the HIV genome |
EP0455905B1 (en) | 1990-05-11 | 1998-06-17 | Microprobe Corporation | Dipsticks for nucleic acid hybridization assays and methods for covalently immobilizing oligonucleotides |
IE66205B1 (en) | 1990-06-14 | 1995-12-13 | Paul A Bartlett | Polypeptide analogs |
US5650489A (en) | 1990-07-02 | 1997-07-22 | The Arizona Board Of Regents | Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof |
US5218105A (en) | 1990-07-27 | 1993-06-08 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US5688941A (en) | 1990-07-27 | 1997-11-18 | Isis Pharmaceuticals, Inc. | Methods of making conjugated 4' desmethyl nucleoside analog compounds |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
WO1992002258A1 (en) | 1990-07-27 | 1992-02-20 | Isis Pharmaceuticals, Inc. | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5138045A (en) | 1990-07-27 | 1992-08-11 | Isis Pharmaceuticals | Polyamine conjugated oligonucleotides |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
AU667459B2 (en) | 1990-08-03 | 1996-03-28 | Sanofi | Compounds and methods for inhibiting gene expression |
US5245022A (en) | 1990-08-03 | 1993-09-14 | Sterling Drug, Inc. | Exonuclease resistant terminally substituted oligonucleotides |
US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
US5512667A (en) | 1990-08-28 | 1996-04-30 | Reed; Michael W. | Trifunctional intermediates for preparing 3'-tailed oligonucleotides |
US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
CA2092002A1 (en) | 1990-09-20 | 1992-03-21 | Mark Matteucci | Modified internucleoside linkages |
US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
WO1992008728A1 (en) | 1990-11-08 | 1992-05-29 | Hybridon, Inc. | Incorporation of multiple reporter groups on synthetic oligonucleotides |
WO1992008796A1 (en) | 1990-11-13 | 1992-05-29 | Immunex Corporation | Bifunctional selectable fusion genes |
JP3220180B2 (ja) | 1991-05-23 | 2001-10-22 | 三菱化学株式会社 | 薬剤含有タンパク質結合リポソーム |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5371241A (en) | 1991-07-19 | 1994-12-06 | Pharmacia P-L Biochemicals Inc. | Fluorescein labelled phosphoramidites |
US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
US6307040B1 (en) | 1992-03-05 | 2001-10-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
US5474796A (en) | 1991-09-04 | 1995-12-12 | Protogene Laboratories, Inc. | Method and apparatus for conducting an array of chemical reactions on a support surface |
US5521291A (en) | 1991-09-30 | 1996-05-28 | Boehringer Ingelheim International, Gmbh | Conjugates for introducing nucleic acid into higher eucaryotic cells |
NZ244306A (en) | 1991-09-30 | 1995-07-26 | Boehringer Ingelheim Int | Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation |
US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
US5661134A (en) | 1991-10-15 | 1997-08-26 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity |
EP0538194B1 (de) | 1991-10-17 | 1997-06-04 | Novartis AG | Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte |
US6335434B1 (en) | 1998-06-16 | 2002-01-01 | Isis Pharmaceuticals, Inc., | Nucleosidic and non-nucleosidic folate conjugates |
US5605662A (en) | 1993-11-01 | 1997-02-25 | Nanogen, Inc. | Active programmable electronic devices for molecular biological analysis and diagnostics |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
US5700922A (en) | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
US5595726A (en) | 1992-01-21 | 1997-01-21 | Pharmacyclics, Inc. | Chromophore probe for detection of nucleic acid |
US5565552A (en) | 1992-01-21 | 1996-10-15 | Pharmacyclics, Inc. | Method of expanded porphyrin-oligonucleotide conjugate synthesis |
FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
IL101600A (en) | 1992-04-15 | 2000-02-29 | Yissum Res Dev Co | Synthetic partially phosphorothioated antisense oligodeoxynucleotides and pharmaceutical compositions containing them |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
US5272250A (en) | 1992-07-10 | 1993-12-21 | Spielvogel Bernard F | Boronated phosphoramidate compounds |
US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
US5288514A (en) | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
EP0636696B1 (en) | 1992-10-15 | 2002-09-04 | Toray Industries, Inc. | Process for producing recombinant major histocompatibility antigen class ii protein in microorganisms |
US5583020A (en) | 1992-11-24 | 1996-12-10 | Ribozyme Pharmaceuticals, Inc. | Permeability enhancers for negatively charged polynucleotides |
US5574142A (en) | 1992-12-15 | 1996-11-12 | Microprobe Corporation | Peptide linkers for improved oligonucleotide delivery |
JP3351476B2 (ja) | 1993-01-22 | 2002-11-25 | 三菱化学株式会社 | リン脂質誘導体及びそれを含有するリポソーム |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
DK0691968T3 (da) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse |
WO1994022891A1 (en) | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides with amide linkages replacing phosphodiester linkages |
DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
US5462854A (en) | 1993-04-19 | 1995-10-31 | Beckman Instruments, Inc. | Inverse linkage oligonucleotides for chemical and enzymatic processes |
NZ266386A (en) | 1993-05-11 | 1997-11-24 | Univ North Carolina | Use of antisense rna oligonucleotides in regulating gene expression |
JPH09500783A (ja) | 1993-05-21 | 1997-01-28 | ターゲッティッド ジェネティクス コーポレイション | シトシンデアミナーゼ(cd)遺伝子に基づく二機能性選択融合遺伝子 |
US5534259A (en) | 1993-07-08 | 1996-07-09 | Liposome Technology, Inc. | Polymer compound and coated particle composition |
CZ287157B6 (en) * | 1993-07-13 | 2000-10-11 | Rhone Poulenc Rorer Sa | Defective recombinant adenovirus and pharmaceutical preparation in which said adenovirus is comprised |
US5417978A (en) | 1993-07-29 | 1995-05-23 | Board Of Regents, The University Of Texas System | Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use |
EP0728139B1 (en) | 1993-09-03 | 2003-08-13 | Isis Pharmaceuticals, Inc. | Amine-derivatized nucleosides and oligonucleosides |
US5491084A (en) | 1993-09-10 | 1996-02-13 | The Trustees Of Columbia University In The City Of New York | Uses of green-fluorescent protein |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
AU1061395A (en) | 1993-11-30 | 1995-06-19 | Mcgill University | Inhibition of dna methyltransferase |
US5908779A (en) | 1993-12-01 | 1999-06-01 | University Of Connecticut | Targeted RNA degradation using nuclear antisense RNA |
US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
KR100386337B1 (ko) | 1993-12-09 | 2004-03-24 | 토마스 제퍼슨 대학교 | 진핵세포에서부위-특이적돌연변이를위한화합물과그방법 |
US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
US5593853A (en) | 1994-02-09 | 1997-01-14 | Martek Corporation | Generation and screening of synthetic drug libraries |
WO1995022618A1 (en) | 1994-02-22 | 1995-08-24 | Dana-Farber Cancer Institute | Nucleic acid delivery system, method of synthesis and uses thereof |
US5902880A (en) | 1994-08-19 | 1999-05-11 | Ribozyme Pharmaceuticals, Inc. | RNA polymerase III-based expression of therapeutic RNAs |
US5539083A (en) | 1994-02-23 | 1996-07-23 | Isis Pharmaceuticals, Inc. | Peptide nucleic acid combinatorial libraries and improved methods of synthesis |
US6551618B2 (en) | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
US6015880A (en) | 1994-03-16 | 2000-01-18 | California Institute Of Technology | Method and substrate for performing multiple sequential reactions on a matrix |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
US5525711A (en) | 1994-05-18 | 1996-06-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Pteridine nucleotide analogs as fluorescent DNA probes |
US5807522A (en) | 1994-06-17 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for fabricating microarrays of biological samples |
US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
US5525735A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies Nv | Methods for synthesizing diverse collections of pyrrolidine compounds |
US5549974A (en) | 1994-06-23 | 1996-08-27 | Affymax Technologies Nv | Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof |
US5597696A (en) | 1994-07-18 | 1997-01-28 | Becton Dickinson And Company | Covalent cyanine dye oligonucleotide conjugates |
US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
US5580731A (en) | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
US5591721A (en) | 1994-10-25 | 1997-01-07 | Hybridon, Inc. | Method of down-regulating gene expression |
US6645943B1 (en) | 1994-10-25 | 2003-11-11 | Hybridon, Inc. | Method of down-regulating gene expression |
US5512295A (en) | 1994-11-10 | 1996-04-30 | The Board Of Trustees Of The Leland Stanford Junior University | Synthetic liposomes for enhanced uptake and delivery |
GB9501465D0 (en) | 1995-01-25 | 1995-03-15 | King S College London | Nucleoside phosphorothioate derivatives,synthesis and use thereof |
DE19502912A1 (de) | 1995-01-31 | 1996-08-01 | Hoechst Ag | G-Cap Stabilisierte Oligonucleotide |
IT1275862B1 (it) | 1995-03-03 | 1997-10-24 | Consiglio Nazionale Ricerche | Trascritto antisenso associato ad alcuni tipi di cellule tumorali ed oligodeossinucleotidi sintetici utili nella diagnosi e nel trattamento |
IT1276642B1 (it) | 1995-03-03 | 1997-11-03 | Consiglio Nazionale Ricerche | Trascritto antisenso presente in linfociti b ed oligodeossinucleotidi sintetici utili per inibirne l'azione |
US5543165A (en) | 1995-06-06 | 1996-08-06 | Hill; Julie B. | Process of making a soluble tea product with champagne-like properties |
US5739311A (en) | 1995-06-07 | 1998-04-14 | Gen-Probe Incorporated | Enzymatic synthesis of phosphorothioate oligonucleotides using restriction endonucleases |
EP2258726A1 (en) | 1995-06-14 | 2010-12-08 | The Regents of the University of California | High affinity human antibodies to c-erbB-2 |
US5569588A (en) | 1995-08-09 | 1996-10-29 | The Regents Of The University Of California | Methods for drug screening |
US5652356A (en) | 1995-08-17 | 1997-07-29 | Hybridon, Inc. | Inverted chimeric and hybrid oligonucleotides |
CA2238829A1 (en) * | 1995-11-30 | 1997-06-05 | Board Of Regents, The University Of Texas System | Methods and compositions for the diagnosis and treatment of cancer |
CA2246229C (en) | 1996-02-14 | 2011-08-23 | Isis Pharmaceuticals Inc. | Sugar-modified gapped oligonucleotides |
PT888385E (pt) | 1996-03-14 | 2004-01-30 | Genentech Inc | Utilizacoes de gdnf e de receptores de gdnf |
KR20000005561A (ko) | 1996-04-17 | 2000-01-25 | 아로넥스 파마슈티칼즈, 인코포레이티드 | 혈관 내피 성장 인자(vegf/vpf) 발현의 안티센스 억제제 |
US5786213A (en) | 1996-04-18 | 1998-07-28 | Board Of Regents, The University Of Texas System | Inhibition of endogenous gastrin expression for treatment of colorectal cancer |
US5756710A (en) | 1996-06-05 | 1998-05-26 | The Trustees Of Columbia University In City Of New York | Phosphorothioate oligonucleotides that bind to the V3-loop and uses thereof |
US20070275921A1 (en) * | 1996-06-06 | 2007-11-29 | Isis Pharmaceuticals, Inc. | Oligomeric Compounds That Facilitate Risc Loading |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20040161777A1 (en) * | 1996-06-06 | 2004-08-19 | Baker Brenda F. | Modified oligonucleotides for use in RNA interference |
US5849902A (en) | 1996-09-26 | 1998-12-15 | Oligos Etc. Inc. | Three component chimeric antisense oligonucleotides |
US5739119A (en) | 1996-11-15 | 1998-04-14 | Galli; Rachel L. | Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA |
US7008776B1 (en) | 1996-12-06 | 2006-03-07 | Aventis Pharmaceuticals Inc. | Compositions and methods for effecting the levels of high density lipoprotein (HDL) cholesterol and apolipoprotein AI very low density lipoprotein (VLDL) cholesterol and low density lipoprotein (LDL) cholesterol |
US7235653B2 (en) | 1996-12-31 | 2007-06-26 | Isis Pharmaceuticals, Inc. | Oligonucleotide compositions and methods for the modulation of the expression of B7 protein |
US6127533A (en) * | 1997-02-14 | 2000-10-03 | Isis Pharmaceuticals, Inc. | 2'-O-aminooxy-modified oligonucleotides |
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 |
DE19710159A1 (de) * | 1997-03-12 | 1998-10-01 | Hoechst Ag | In vitro Transkriptionsverfahren zum Screening von Naturstoffen und anderen chemischen Substanzen |
US6013786A (en) | 1997-08-22 | 2000-01-11 | Hybridon, Inc. | MDM2-specific antisense oligonucleotides |
US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
AU9063398A (en) | 1997-09-12 | 1999-04-05 | Exiqon A/S | Oligonucleotide analogues |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US7285288B1 (en) | 1997-10-03 | 2007-10-23 | Board Of Regents, The University Of Texas System | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
US7294459B1 (en) | 1997-10-15 | 2007-11-13 | President And Fellows Of Harvard College | Cell regulatory genes, encoded products, and uses related thereto |
US6034883A (en) | 1998-01-29 | 2000-03-07 | Tinney; Charles E. | Solid state director for beams |
US6175409B1 (en) | 1999-04-02 | 2001-01-16 | Symyx Technologies, Inc. | Flow-injection analysis and variable-flow light-scattering methods and apparatus for characterizing polymers |
US7321828B2 (en) | 1998-04-13 | 2008-01-22 | Isis Pharmaceuticals, Inc. | System of components for preparing oligonucleotides |
US20040186071A1 (en) | 1998-04-13 | 2004-09-23 | Bennett C. Frank | Antisense modulation of CD40 expression |
US20030228597A1 (en) * | 1998-04-13 | 2003-12-11 | Cowsert Lex M. | Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation |
US6221587B1 (en) | 1998-05-12 | 2001-04-24 | Isis Pharmceuticals, Inc. | Identification of molecular interaction sites in RNA for novel drug discovery |
US6833361B2 (en) | 1998-05-26 | 2004-12-21 | Ribapharm, Inc. | Nucleosides having bicyclic sugar moiety |
CN1311630A (zh) | 1998-05-26 | 2001-09-05 | Icn药品公司 | 具有双环糖部分的新核苷类 |
WO1999066946A1 (en) * | 1998-06-24 | 1999-12-29 | Trustees Of The University Of Pennsylvania | Compositions and methods for inducing apoptosis in e6-expressing cells |
US20030139359A1 (en) | 2001-12-04 | 2003-07-24 | Isis Pharmaceuticals Inc. | Antisense modulation of phospholipid scramblase 3 expression |
US6100090A (en) | 1999-06-25 | 2000-08-08 | Isis Pharmaceuticals Inc. | Antisense inhibition of PI3K p85 expression |
US6242589B1 (en) | 1998-07-14 | 2001-06-05 | Isis Pharmaceuticals, Inc. | Phosphorothioate oligonucleotides having modified internucleoside linkages |
US6867294B1 (en) | 1998-07-14 | 2005-03-15 | Isis Pharmaceuticals, Inc. | Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages |
US6214986B1 (en) | 1998-10-07 | 2001-04-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of bcl-x expression |
WO2000027424A2 (en) | 1998-11-06 | 2000-05-18 | Alcon Laboratories, Inc. | Upregulation of endogenous prostaglandins to lower intraocular pressure |
US5985663A (en) | 1998-11-25 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of interleukin-15 expression |
ATE300959T1 (de) | 1999-01-27 | 2005-08-15 | Becker David Dr | Formulierungen enthaltend antisense nukleotide spezifisch für connexine |
NZ513402A (en) | 1999-02-12 | 2003-06-30 | Sankyo Co | Novel nucleosides and oligonucleotide analogues |
CA2371814C (en) | 1999-02-26 | 2014-05-27 | The University Of British Columbia | Trpm-2 antisense therapy |
CA2367955C (en) | 1999-03-15 | 2009-05-19 | University Of British Columbia | Abc1 polypeptide and methods and reagents for modulating cholesterol levels |
US20040137423A1 (en) | 1999-03-15 | 2004-07-15 | Hayden Michael R. | Compositions and methods for modulating HDL cholesterol and triglyceride levels |
WO2000056916A2 (en) | 1999-03-18 | 2000-09-28 | Exiqon A/S | Detection of mutations in genes by specific lna primers |
US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
US6734291B2 (en) | 1999-03-24 | 2004-05-11 | Exiqon A/S | Synthesis of [2.2.1]bicyclo nucleosides |
ATE332909T1 (de) | 1999-03-24 | 2006-08-15 | Exiqon As | Verbesserte synthese für 2.2.1.öbicyclo- nukleoside |
EP1171078A4 (en) | 1999-03-26 | 2002-11-06 | Aventis Pharma Inc | COMPOSITIONS AND METHODS FOR INFLUENCING THE BLOOD LEVELS OF HIGH DENSITY LIPOPROTEIN (HDL) CHOLESTEROL AND APOLIPOPROTEIN AI, VERY LOW DENSITY LIPOROTEIN (VLDL) CHOLESTEROL AND LOW DENSITY LIPOPROTEIN (LDL) CHOLESTER |
AU4077100A (en) | 1999-04-08 | 2000-11-14 | Chiron Corporation | Enhancement of the immune response for vaccine and gene therapy applications |
AU4657500A (en) | 1999-04-21 | 2000-11-02 | Pangene Corporation | Locked nucleic acid hybrids and methods of use |
CN102180924A (zh) | 1999-05-04 | 2011-09-14 | 桑塔里斯制药公司 | L-核糖-lna类似物 |
US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
DE19925073C2 (de) | 1999-06-01 | 2001-07-19 | Stefan Weiss | Nucleinsäuremoleküle mit spezifischer Erkennung von nativem PrP·S··c·, Herstellung und Verwendung |
US6656730B1 (en) | 1999-06-15 | 2003-12-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides conjugated to protein-binding drugs |
WO2001000669A2 (en) | 1999-06-25 | 2001-01-04 | Genset | A bap28 gene and protein |
US20040006031A1 (en) | 2002-07-02 | 2004-01-08 | Isis Pharmaceuticals Inc. | Antisense modulation of HMG-CoA reductase expression |
US6147200A (en) | 1999-08-19 | 2000-11-14 | Isis Pharmaceuticals, Inc. | 2'-O-acetamido modified monomers and oligomers |
WO2001021631A2 (en) | 1999-09-20 | 2001-03-29 | Millennium Pharmaceuticals, Inc. | Secreted proteins and uses thereof |
MXPA02003108A (es) * | 1999-09-25 | 2003-10-14 | Univ Iowa Res Found | Acidos nucleicos inmunoestimuladores. |
US6617442B1 (en) | 1999-09-30 | 2003-09-09 | Isis Pharmaceuticals, Inc. | Human Rnase H1 and oligonucleotide compositions thereof |
US6528262B1 (en) | 1999-10-06 | 2003-03-04 | Quark Biotech, Inc. | Method for enrichment of natural antisense messenger RNA |
US6986988B2 (en) | 1999-10-06 | 2006-01-17 | Quark Biotech, Inc. | Method for enrichment of natural antisense messenger RNA |
JP4377494B2 (ja) * | 1999-10-22 | 2009-12-02 | 東芝テック株式会社 | 情報入力装置 |
AU2778801A (en) | 2000-01-07 | 2001-07-24 | Baylor University | Antisense compositions and methods |
WO2001051490A1 (en) | 2000-01-14 | 2001-07-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Methanocarba cycloalkyl nucleoside analogues |
US6303374B1 (en) | 2000-01-18 | 2001-10-16 | Isis Pharmaceuticals Inc. | Antisense modulation of caspase 3 expression |
US6287860B1 (en) | 2000-01-20 | 2001-09-11 | Isis Pharmaceuticals, Inc. | Antisense inhibition of MEKK2 expression |
JP2001247459A (ja) | 2000-03-03 | 2001-09-11 | Oakland Uniservices Ltd | 癌の組み合わせ療法 |
KR20030003240A (ko) | 2000-03-27 | 2003-01-09 | 유니버시티 오브 델라웨어 | 개질된 단일 가닥 올리고뉴클레오티드를 이용한 표적염색체 게놈 변경법 |
US6936467B2 (en) | 2000-03-27 | 2005-08-30 | University Of Delaware | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides |
US7402434B2 (en) | 2000-05-08 | 2008-07-22 | Newman Stuart A | Splice choice antagonists as therapeutic agents |
US20030176341A1 (en) | 2000-06-29 | 2003-09-18 | Jean-Francois Meritet | Interferon-alpha induced gene |
EP1311262A4 (en) | 2000-07-28 | 2005-06-01 | Cancer Rec Tech Ltd | COMBINED TREATMENT AGAINST CANCER |
AU2001282522A1 (en) | 2000-08-29 | 2002-03-13 | Takeshi Imanishi | Novel nucleoside analogs and oligonucleotide derivatives containing these analogs |
ES2300366T3 (es) | 2000-09-02 | 2008-06-16 | Grunenthal Gmbh | Oligonucleotidos antisentido contra el vr1. |
US6444464B1 (en) | 2000-09-08 | 2002-09-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of E2F transcription factor 2 expression |
JP2004509619A (ja) | 2000-09-20 | 2004-04-02 | アイシス・ファーマシューティカルス・インコーポレーテッド | Flip−c発現のアンチセンスモジュレーション |
CA2422934A1 (en) | 2000-10-13 | 2002-04-18 | Institut De Cardiologie De Montreal | Antisense oligonucleotides directed toward mammalian vegf receptor genes and uses thereof |
US20030228618A1 (en) | 2000-11-24 | 2003-12-11 | Erez Levanon | Methods and systems for identifying naturally occurring antisense transcripts and methods, kits and arrays utilizing same |
US20050222029A1 (en) | 2001-01-04 | 2005-10-06 | Myriad Genetics, Incorporated | Compositions and methods for treating diseases |
US7423142B2 (en) | 2001-01-09 | 2008-09-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
WO2002068470A2 (en) | 2001-02-26 | 2002-09-06 | Pharma Pacific Pty Ltd | Interferon-alpha induced gene |
US20020147165A1 (en) | 2001-02-22 | 2002-10-10 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
WO2002085309A2 (en) * | 2001-04-24 | 2002-10-31 | Epigenesis Pharmaceuticals, Inc. | Composition, formulations & kits for treatment of respiratory & lung disease with anti-sense oligonucleotides & a bronchodilating agent |
AUPR497101A0 (en) | 2001-05-14 | 2001-06-07 | Queensland University Of Technology | Polynucleotides and polypeptides linked to cancer and/or tumorigenesi |
IL143379A (en) | 2001-05-24 | 2013-11-28 | Yissum Res Dev Co | Oligonucleotide against human ache isoform r and its uses |
US7053195B1 (en) | 2001-06-12 | 2006-05-30 | Syngenta Participatious Ag | Locked nucleic acid containing heteropolymers and related methods |
US7153954B2 (en) | 2001-07-12 | 2006-12-26 | Santaris Pharma A/S | Method for preparation of LNA phosphoramidites |
EP2360251B1 (en) | 2001-07-12 | 2016-09-28 | University of Massachusetts | In vivo production of small interfering RNAs that mediate gene silencing |
US7425545B2 (en) | 2001-07-25 | 2008-09-16 | Isis Pharmaceuticals, Inc. | Modulation of C-reactive protein expression |
US20030096772A1 (en) | 2001-07-30 | 2003-05-22 | Crooke Rosanne M. | Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression |
US7259150B2 (en) | 2001-08-07 | 2007-08-21 | Isis Pharmaceuticals, Inc. | Modulation of apolipoprotein (a) expression |
WO2003020739A2 (en) | 2001-09-04 | 2003-03-13 | Exiqon A/S | Novel lna compositions and uses thereof |
WO2003025010A2 (en) | 2001-09-17 | 2003-03-27 | Eirx Therapeutics Limited | Human delta-n p73 molecules and uses thereof |
WO2003025177A2 (fr) * | 2001-09-17 | 2003-03-27 | Molecular Engines Laboratories | Sequences impliquees dans les phenomenes de suppression tumorale, reversion tumorale, apoptose et/ou resistance aux virus et leur utilisation comme medicaments |
US20040214766A1 (en) | 2001-10-01 | 2004-10-28 | Kari Alitalo | VEGF-C or VEGF-D materials and methods for treatment of neuropathologies |
CA2457821A1 (en) | 2001-10-10 | 2003-04-24 | Societe Des Produits Nestle S.A. | Coffee plant with reduced .alpha.-d-galactosidase activity |
AR037699A1 (es) | 2001-12-04 | 2004-12-01 | Monsanto Technology Llc | Maiz transgenico con fenotipo mejorado |
US7125982B1 (en) | 2001-12-05 | 2006-10-24 | Frayne Consultants | Microbial production of nuclease resistant DNA, RNA, and oligo mixtures |
US6965025B2 (en) | 2001-12-10 | 2005-11-15 | Isis Pharmaceuticals, Inc. | Antisense modulation of connective tissue growth factor expression |
CA2365811A1 (en) | 2001-12-21 | 2003-06-21 | Institut De Cardiologie | A new gene therapy using antisense strategy to estrogen receptors (er .alpha. and/or er .beta.) to optimize vascular healing and cardioprotection after vascular injury |
GB0130955D0 (en) | 2001-12-24 | 2002-02-13 | Cancer Res Ventures | Expression system |
KR20030056538A (ko) | 2001-12-28 | 2003-07-04 | 주식회사 웰진 | 리본형 안티센스 올리고뉴클레오티드에 의한 형질전이성장 인자-β1의 효과적 저해제 개발 |
US20030191075A1 (en) | 2002-02-22 | 2003-10-09 | Cook Phillip Dan | Method of using modified oligonucleotides for hepatic delivery |
AU2003212729A1 (en) | 2002-02-25 | 2003-09-09 | Gunnar Norstedt | Vitamin d upregulated protein 1 (vdup-1) methods and uses thereof |
EP1483280B1 (en) | 2002-03-08 | 2012-10-24 | Glen Research Corporation | Fluorescent nitrogenous base and nucleosides incorporating same |
GB2386836B (en) | 2002-03-22 | 2006-07-26 | Cancer Res Ventures Ltd | Anti-cancer combinations |
US7169916B2 (en) | 2002-04-01 | 2007-01-30 | Isis Pharmaceuticals, Inc. | Chloral-free DCA in oligonucleotide synthesis |
US20050215504A1 (en) | 2002-04-02 | 2005-09-29 | Bennett C F | Antisense modulation of sterol regulatory element-binding protein-1 expression |
EP1501930A2 (en) | 2002-04-05 | 2005-02-02 | Santaris Pharma A/S | Oligomeric compounds for the modulation hif-1alpha expression |
US6808906B2 (en) | 2002-05-08 | 2004-10-26 | Rigel Pharmaceuticals, Inc. | Directionally cloned random cDNA expression vector libraries, compositions and methods of use |
US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
US7199107B2 (en) | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
US20040033480A1 (en) | 2002-08-15 | 2004-02-19 | Wong Norman C.W. | Use of resveratrol to regulate expression of apolipoprotein A1 |
NZ538259A (en) | 2002-09-10 | 2008-03-28 | Samuel Roberts Noble Found Inc | Methods and compositions for production of flavonoid and isoflavonoid nutraceuticals |
JP2006500070A (ja) | 2002-09-25 | 2006-01-05 | ファルマシア・コーポレーション | ファルネソイドx受容体発現のアンチセンス調節 |
EP2272958A1 (en) | 2002-09-26 | 2011-01-12 | ISIS Pharmaceuticals, Inc. | Modulation of forkhead box O1A expression |
GB2394658A (en) | 2002-11-01 | 2004-05-05 | Cancer Rec Tech Ltd | Oral anti-cancer composition |
CA2504926C (en) | 2002-11-01 | 2014-01-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for sirna inhibition of hif-1 alpha |
WO2004041838A1 (en) | 2002-11-01 | 2004-05-21 | University Of Massachusetts | Regulation of transcription elongation factors |
CA2504694C (en) | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
WO2004044136A2 (en) * | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2’-modified nucleosides for use in gene modulation |
AU2003291721A1 (en) * | 2002-11-05 | 2004-06-03 | Isis Pharmaceuticals, Inc. | Phosphorous-linked oligomeric compounds and their use in gene modulation |
US20060009410A1 (en) | 2002-11-13 | 2006-01-12 | Crooke Rosanne M | Effects of apolipoprotein B inhibition on gene expression profiles in animals |
EP1560931B1 (en) * | 2002-11-14 | 2011-07-27 | Dharmacon, Inc. | Functional and hyperfunctional sirna |
ES2607471T3 (es) | 2002-11-18 | 2017-03-31 | Roche Innovation Center Copenhagen A/S | Diseño antisentido |
US7314750B2 (en) * | 2002-11-20 | 2008-01-01 | Affymetrix, Inc. | Addressable oligonucleotide array of the rat genome |
US7144999B2 (en) | 2002-11-23 | 2006-12-05 | Isis Pharmaceuticals, Inc. | Modulation of hypoxia-inducible factor 1 alpha expression |
US7713738B2 (en) | 2003-02-10 | 2010-05-11 | Enzon Pharmaceuticals, Inc. | Oligomeric compounds for the modulation of survivin expression |
US7598227B2 (en) | 2003-04-16 | 2009-10-06 | Isis Pharmaceuticals Inc. | Modulation of apolipoprotein C-III expression |
US7339051B2 (en) | 2003-04-28 | 2008-03-04 | Isis Pharmaceuticals, Inc. | Compositions and methods for the treatment of severe acute respiratory syndrome (SARS) |
JP2006525811A (ja) * | 2003-05-16 | 2006-11-16 | ロゼッタ インファーマティクス エルエルシー | Rna干渉の方法と組成物 |
US7276599B2 (en) | 2003-06-02 | 2007-10-02 | Isis Pharmaceuticals, Inc. | Oligonucleotide synthesis with alternative solvents |
AU2004253455B2 (en) | 2003-06-03 | 2011-03-03 | Eli Lilly And Company | Modulation of survivin expression |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
TW200519202A (en) | 2003-09-18 | 2005-06-16 | Lilly Co Eli | Modulation of eIF4E expression |
US20070009899A1 (en) * | 2003-10-02 | 2007-01-11 | Mounts William M | Nucleic acid arrays for detecting gene expression in animal models of inflammatory diseases |
US8258105B2 (en) | 2003-10-07 | 2012-09-04 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides optimized for kidney targeting |
WO2005045034A2 (en) | 2003-10-23 | 2005-05-19 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED TREATMENT OF PARKINSON DISEASE USING SHORT INTERERING NUCLEIC ACID (siNA) |
KR20070006709A (ko) | 2003-12-23 | 2007-01-11 | 산타리스 팔마 에이/에스 | Bcl-2의 조절을 위한 올리고머 화합물 |
CA2553199C (en) | 2004-01-12 | 2014-03-25 | The Trustees Of The University Of Pennsylvania | System for up-regulating bone morphogenetic protein (bmp) gene expression in bone cells via the application of fields generated by specific electric and electromagnetic signals |
US7468431B2 (en) | 2004-01-22 | 2008-12-23 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E-BP2 expression |
GB0403041D0 (en) | 2004-02-11 | 2004-03-17 | Milner Anne J | Induction of apoptosis |
US20050221354A1 (en) * | 2004-02-18 | 2005-10-06 | Wyeth | Nucleic acid arrays for monitoring expression profiles of drug target genes |
EP1566202A1 (en) | 2004-02-23 | 2005-08-24 | Sahltech I Göteborg AB | Use of resistin antagonists in the treatment of rheumatoid arthritis |
US7402574B2 (en) | 2004-03-12 | 2008-07-22 | Avi Biopharma, Inc. | Antisense composition and method for treating cancer |
US8394947B2 (en) * | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
US7297786B2 (en) | 2004-07-09 | 2007-11-20 | University Of Iowa Research Foundation | RNA interference in respiratory epitheial cells |
US7427675B2 (en) | 2004-08-23 | 2008-09-23 | Isis Pharmaceuticals, Inc. | Compounds and methods for the characterization of oligonucleotides |
WO2006034573A1 (en) * | 2004-09-27 | 2006-04-06 | Med Biogene Inc. | Hematological cancer profiling system |
ZA200704254B (en) * | 2004-11-09 | 2009-09-30 | Santaris Pharma As | LNA oligonucleotides and the treatment of cancer |
US7589190B2 (en) | 2004-11-09 | 2009-09-15 | Enzon Pharmaceuticals, Inc. | Potent LNA oligonucleotides for the inhibition of HIF-1A expression |
US7220549B2 (en) | 2004-12-30 | 2007-05-22 | Helicos Biosciences Corporation | Stabilizing a nucleic acid for nucleic acid sequencing |
WO2007002718A2 (en) | 2005-06-27 | 2007-01-04 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of hif-1 and theraputic uses thereof |
US20070213292A1 (en) * | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
WO2007028065A2 (en) | 2005-08-30 | 2007-03-08 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
EP2325315B1 (en) | 2005-10-28 | 2014-05-07 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of huntingtin gene |
WO2007056326A2 (en) | 2005-11-04 | 2007-05-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of nav1.8 gene |
EP1957648B1 (en) * | 2005-11-17 | 2014-04-23 | Board of Regents, The University of Texas System | Modulation of gene expression by oligomers targeted to chromosomal dna |
EP1957109A2 (en) | 2005-12-02 | 2008-08-20 | Sirtris Pharmaceuticals, Inc. | Modulators of cdc2-like kinases (clks) and methods of use thereof |
US20070231816A1 (en) | 2005-12-09 | 2007-10-04 | Baylor Research Institute | Module-Level Analysis of Peripheral Blood Leukocyte Transcriptional Profiles |
CN100356377C (zh) | 2005-12-20 | 2007-12-19 | 无锡永中科技有限公司 | 文档显示方法 |
WO2007071824A1 (en) | 2005-12-20 | 2007-06-28 | Oy Jurilab Ltd | Novel genes and markers associated with high-density lipoprotein -cholesterol (hdl-c) |
US8288354B2 (en) * | 2005-12-28 | 2012-10-16 | The Scripps Research Institute | Natural antisense and non-coding RNA transcripts as drug targets |
ES2516815T3 (es) | 2006-01-27 | 2014-10-31 | Isis Pharmaceuticals, Inc. | Análogos de ácidos nucleicos bicíclicos modificados en la posición 6 |
US7569686B1 (en) | 2006-01-27 | 2009-08-04 | Isis Pharmaceuticals, Inc. | Compounds and methods for synthesis of bicyclic nucleic acid analogs |
NZ587704A (en) | 2006-03-31 | 2012-04-27 | Alnylam Pharmaceuticals Inc | Use of dsRNA for inhibiting expression of Eg5 gene |
CA2651042A1 (en) | 2006-05-05 | 2007-12-13 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of sglt2 |
ES2392478T3 (es) | 2006-05-11 | 2012-12-11 | Alnylam Pharmaceuticals Inc. | Composiciones y métodos para inhibir la expresión del gen PCSK9 |
US7666854B2 (en) | 2006-05-11 | 2010-02-23 | Isis Pharmaceuticals, Inc. | Bis-modified bicyclic nucleic acid analogs |
AU2007249349B2 (en) | 2006-05-11 | 2012-03-08 | Isis Pharmaceuticals, Inc. | 5'-Modified bicyclic nucleic acid analogs |
EP1867338A1 (en) | 2006-05-30 | 2007-12-19 | Université Libre De Bruxelles | Pharmaceutical composition comprising apolipoproteins for the treatment of human diseases |
US20080199961A1 (en) * | 2006-08-25 | 2008-08-21 | Avi Biopharma, Inc. | ANTISENSE COMPOSITION AND METHOD FOR INHIBITION OF miRNA BIOGENESIS |
WO2008066672A2 (en) | 2006-11-06 | 2008-06-05 | Beth Israel Deaconess Medical Center | Identification and use of small molecules to modulate transcription factor function and to treat transcription factor associated diseases |
WO2008057556A2 (en) | 2006-11-06 | 2008-05-15 | Beth Israel Deaconess Medical Center | Identification and use of small molecules to modulate ese-1 transcription factor function and to treat ese-1 transcription factor associated diseases |
US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
US20100169996A1 (en) | 2007-01-19 | 2010-07-01 | Lionel Navarro | Methods and compositions for modulating the sirna and rna-directed-dna methylation pathways |
CA2686933A1 (en) | 2007-04-06 | 2008-10-16 | The Johns Hopkins University | Methods and compositions for the treatment of cancer |
US20080293142A1 (en) | 2007-04-19 | 2008-11-27 | The Board Of Regents For Oklahoma State University | Multiple shRNA Expression Vectors and Methods of Construction |
ES2563485T3 (es) | 2008-07-01 | 2016-03-15 | Monsanto Technology Llc | Construcciones de ADN recombinante y procedimientos para modular la expresión de un gen diana |
ES2727549T3 (es) | 2008-10-03 | 2019-10-17 | Curna Inc | Tratamiento de las enfermedades relacionadas con la apolipoproteína a1 por inhibición del transcrito antisentido natural a la apolipoproteína a1 |
EP2177615A1 (en) | 2008-10-10 | 2010-04-21 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases |
US8606289B2 (en) | 2008-11-10 | 2013-12-10 | Qualcomm Incorporated | Power headroom-sensitive scheduling |
JP2012509306A (ja) | 2008-11-22 | 2012-04-19 | ザ ユニバーシティ オブ ブリストル | VEGFxxxbの新規な使用 |
CA2745811C (en) | 2008-12-04 | 2021-07-13 | Joseph Collard | Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene |
US9209196B2 (en) | 2011-11-30 | 2015-12-08 | Sharp Kabushiki Kaisha | Memory circuit, method of driving the same, nonvolatile storage device using the same, and liquid crystal display device |
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