JP6189576B2 - Rna干渉を媒介する短鎖rna分子 - Google Patents
Rna干渉を媒介する短鎖rna分子 Download PDFInfo
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- JP6189576B2 JP6189576B2 JP2009210276A JP2009210276A JP6189576B2 JP 6189576 B2 JP6189576 B2 JP 6189576B2 JP 2009210276 A JP2009210276 A JP 2009210276A JP 2009210276 A JP2009210276 A JP 2009210276A JP 6189576 B2 JP6189576 B2 JP 6189576B2
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Description
〔1〕単離された二本鎖RNA分子であって、各鎖が39〜52塩基長を有し、該RNA分子は標的特異的なRNA干渉が可能な1以上の二本鎖断片にプロセシングされることができ、該RNA分子は、第1の鎖が予め決定したmRNA標的分子に対して少なくとも70%の同一性を有する配列からなり、第2の鎖が該第1の鎖に相補的な配列からなる、上記RNA分子。
〔2〕鎖が39塩基長を有する、上記〔1〕に記載のRNA分子。
〔3〕単離された二本鎖RNA分子であって、該RNA分子は標的特異的なRNA干渉が可能なものであり、第1の鎖が19〜25塩基長を有し、予め決定したmRNA標的分子に対して少なくとも70%の同一性を有する配列からなり、第2の鎖が25塩基長を有する、上記RNA分子。
〔4〕なくとも1つの修飾されたリボヌクレオチドを含む、上記〔1〕〜〔3〕のいずれか1つに記載のRNA分子。
〔5〕修飾リボヌクレオチドが、糖、骨格鎖または核酸塩基修飾リボヌクレオチドから選択される、上記〔4〕に記載のRNA分子。
〔6〕修飾リボヌクレオチドが、糖修飾リボヌクレオチドであり、2’−OH基が、H、OR、R、ハロ、SH、SR1、NH2、NHR、NR2またはCNから選択される基で置換され、Rは、C1−C6アルキル、アルケニルまたはアルキニルであり、ハロは、F、Cl、BrまたはIである、上記〔5〕に記載のRNA分子。
〔7〕飾リボヌクレオチドが、ホスホロチオエート基を含む骨格鎖修飾リボヌクレオチドである、上記〔5〕に記載のRNA分子。
〔8〕前記RNA分子の第1の鎖が、予め決定したmRNA標的分子に対して、少なくとも85%の同一性を有する配列からなる、上記〔1〕〜〔7〕のいずれか1つに記載のRNA分子。
〔9〕下記のステップを含む、請求項1〜8のいずれか1項に記載の二本鎖RNA分子の作製方法:
(a)各々が39〜52または19〜25塩基長を有する2本のRNA鎖を合成するステップであって、該RNA鎖は二本鎖RNA分子を形成することができるものである、上記ステップ、
(b)二本鎖RNA分子が形成される条件下で合成RNA鎖を結合させるステップであって、得られる二本鎖RNA分子は標的特異的なRNA干渉が可能なものである、上記ステップ。
〔10〕RNA鎖が化学的に合成される、上記〔9〕に記載の方法。
〔11〕RNA鎖が酵素により合成される、上記〔9〕に記載の方法。
〔12〕下記のステップを含む、動物細胞において標的特異的なRNA干渉を媒介する方法:
(a)標的特異的なRNA干渉が起こりうる条件下で、上記細胞を請求項1〜8のいずれか1項に記載の二本鎖RNA分子と接触させるステップ、および
(b)上記二本鎖RNAと同一の配列部分を有する標的核酸に対する、上記二本鎖RNAにより引き起こされる標的特異的なRNA干渉を媒介するステップ。
〔13〕接触ステップが、二本鎖RNA分子を標的細胞に導入し、そこで標的特異的なRNA干渉を起こさせうるステップを含む、上記〔12〕に記載の方法。
〔14〕導入ステップが、キャリア媒介による送達または注射を含む、上記〔13〕に記載の方法。
〔15〕動物細胞における遺伝子の機能を決定するための、上記〔12〕〜〔14〕のいずれか1つに記載の方法の使用。
〔16〕動物細胞における遺伝子の機能を抑制するための、上記〔12〕〜〔14〕のいずれか1つに記載の方法の使用。
〔17〕遺伝子が病理的状態と関連する、上記〔15〕または〔16〕に記載の使用。
〔18〕遺伝子が病原体関連遺伝子である、上記〔17〕に記載の使用。
〔19〕遺伝子がウイルス遺伝子である、上記〔18〕に記載の使用。
〔20〕遺伝子が腫瘍関連遺伝子である、上記〔17〕に記載の使用。
〔21〕遺伝子が自己免疫疾患関連遺伝子である、上記〔17〕に記載の使用。
〔22〕標的遺伝子特異的ノックアウト表現型を示す動物細胞であって、該細胞が、内因性標的遺伝子の発現を阻害しうる少なくとも1つの二本鎖RNA分子、または少なくとも1つの内因性標的遺伝子の発現を阻害しうる少なくとも1つの二本鎖RNA分子をコードするDNAでトランスフェクトされており、該二本鎖RNA分子は、各RNA鎖が39〜52または19〜25塩基長を有し、少なくとも一方の鎖が1〜3塩基の3’突出部を有し、3’突出部を除く該RNA分子の一方の鎖が、予め決定されたmRNA標的分子に対して100%の同一性を有する配列からなる、上記細胞。
〔23〕哺乳動物細胞である、上記〔22〕に記載の細胞。
〔24〕ヒト細胞である、上記〔23〕に記載の細胞。
〔25〕標的タンパク質、または該標的タンパク質の変異体もしくは突然変異形態をコードする少なくとも1つの外因性標的核酸でさらにトランスフェクトされた、上記〔22〕〜〔24〕のいずれか1つに記載の細胞であって、該外因性標的核酸は、二本鎖RNA分子による該外因性標的核酸の発現の阻害が、内因性標的遺伝子の発現より低いという点で、該内因性標的遺伝子とは核酸レベルで異なるものである、上記細胞。
〔26〕外因性標的核酸が、検出可能なペプチドまたはポリペプチドをコードするさらなる核酸配列と融合されている、上記〔25〕に記載の細胞。
〔27〕分析手法のための、上記〔22〕〜〔26〕のいずれか1つに記載の細胞の使用。
〔28〕遺伝子発現プロフィールを分析するための、上記〔27〕に記載の使用。
〔29〕プロテオーム分析のための、上記〔27〕に記載の使用。
〔30〕外因性標的核酸によってコードされる標識タンパク質の変異体または突然変異形態の分析が実施される、上記〔27〕〜〔29〕のいずれか1つに記載の使用。
〔31〕標的タンパク質の機能ドメインを同定するための、上記〔30〕に記載の使用。
〔32〕下記のものから選択される少なくとも2つの動物細胞の比較を実施する、上記〔27〕〜〔31〕のいずれか1つに記載の使用:
(i)標的遺伝子阻害を含まない対照細胞、
(ii)標的遺伝子阻害を含む細胞、および
(iii)標的遺伝子阻害と、外因性標的核酸による標的遺伝子の相補を含む細胞。
〔33〕分析が、機能および/または表現型の分析を含む、上記〔27〕〜〔32〕のいずれか1つに記載の使用。
〔34〕調製手法のための、上記〔22〕〜〔26〕のいずれか1つに記載の細胞の使用。
〔35〕真核細胞からタンパク質またはタンパク質複合体を単離するための、上記〔34〕に記載の使用。
〔36〕高分子量タンパク質複合体を単離するための、上記〔35〕に記載の使用。
〔37〕高分子量タンパク質複合体が核酸を含む、上記〔36〕に記載の使用。
〔38〕薬理学的物質を同定および/または特性決定する手法における、〔27〕〜〔37〕のいずれか1つに記載の使用。
〔39〕下記の(a)〜(c)を含む、少なくとも1つの標的タンパク質に作用する薬理学的物質の同定および/または特性決定システム:
(a)少なくとも1つの標的タンパク質をコードする少なくとも1つの標的遺伝子を発現することができる、動物細胞、
(b)上記少なくとも1つの内因性標的遺伝子の発現を阻害することができる、少なくとも1つの二本鎖RNA分子であって、該二本鎖RNA分子は、各RNA鎖が39〜52または19〜25塩基長を有し、少なくとも一方の鎖が1〜3塩基の3’突出部を有し、3’突出部を除く該RNA分子の一方の鎖が、予め決定したmRNA標的分子に対して100%の同一性を有する配列からなる、上記RNA分子、および
(c)薬理学的特性を同定および/または特性決定しようとする、試験物質または試験物質のコレクション。
〔40〕さらに下記の(d)を含む、上記〔39〕に記載のシステム:
(d)上記標的タンパク質または該標的タンパク質の変異体もしくは突然変異形態をコードする少なくとも1つの外因性標的核酸であって、該外因性標的核酸は、二本鎖RNA分子による発現の阻害が、上記内因性標的遺伝子の発現より低いという点で、該内因性標的遺伝子とは核酸レベルで異なるものである、上記外因性標的核酸。
(a)各々が19〜25塩基長、例えば19〜23塩基長を有する2本のRNA鎖を合成するステップであって、このRNA鎖は二本鎖RNA分子を形成することができるものであり、好ましくは少なくとも1本が1〜5塩基の3’突出部を有する、上記ステップ、
(b)二本鎖RNA分子が形成される条件下で合成RNA鎖を結合させるステップであって、得られる二本鎖RNA分子は標的特異的な核酸改変、特にRNA干渉および/またはDNAメチル化を媒介することが可能なものである、上記ステップ。
(a)標的特異的な核酸改変が起こりうる条件下で、上記細胞または生物を本発明の二本鎖RNA分子と接触させるステップ、
(b)上記二本鎖RNAと実質的に対応する配列部分を有する標的核酸に対する、上記二本鎖RNAにより引き起こされる標的特異的な核酸改変を媒介するステップ。
(i)標的遺伝子阻害を含まない対照細胞または対照生物、
(ii)標的遺伝子阻害を含む細胞または生物、および
(iii)標的遺伝子阻害と、外因性標的核酸による標的遺伝子の相補を含む細胞または生物。
(a)上記標的タンパク質をコードする少なくとも1つの内因性標的遺伝子を発現することができる、真核細胞またはヒト以外の真核生物、
(b)上記少なくとも1つの内因性標的遺伝子の発現を阻害することができる、少なくとも1つの二本鎖RNA分子、および
(c)薬理学的特性を同定および/または特性決定しようとする、試験物質または試験物質のコレクション。
(d)上記標的タンパク質または該標的タンパク質の変異体もしくは突然変異形態をコードする少なくとも1つの外因性標的核酸であって、この外因性標的核酸は、二本鎖RNA分子による発現の阻害が、上記内因性標的遺伝子の発現より実質的に低いという点で、該内因性標的遺伝子とは核酸レベルで異なるものである、上記外因性標的核酸。
図1:38bpという短い二本鎖RNAは、RNAiを媒介することができる。
RNAiは、主として21および22塩基の短鎖干渉RNA(siRNA)を生成するdsRNA(センス鎖は黒、アンチセンス鎖は赤)のプロセシングで開始すると推定される。短い3’突出塩基が、dsRNA上に存在すれば、これは、短鎖dsRNAのプロセシングに有益であると考えられる。これから特性決定しようとするdsRNAプロセシングタンパク質は、緑色および青色の長円形として表し、非対称にdsRNA上に集合させる。本発明のモデルでは、これは、推定上の青色タンパク質またはタンパク質ドメインと、3’から5’方向のsiRNA鎖との結合により説明されるのに対し、推定上の緑色タンパク質またはタンパク質ドメインは、向き合うsiRNA鎖と必ず結合する。これらのタンパク質またはサブセットは、siRNA二本鎖と会合したままであり、dsRNAプロセシング反応の方向により決定される配向を保存している。青色タンパク質と会合したsiRNA配列だけが標的RNA切断を指示することができる。エンドヌクレアーゼ複合体は、短い干渉リボ核タンパク質複合体またはsiRNPと呼ばれる。本発明では、dsRNAを切断するエンドヌクレアーゼは、恐らく、標的認識に使用されない受動siRNAを一時的に置換することにより、標的RNAも切断することができると推定する。次に、この標的RNAは、配列相補的ガイドsiRNAにより認識される領域の中心部で切断される。
(A)実験戦略の概要。キャップを有し、かつポリアデニル化されたセンス標的mRNAを描くと共に、センスおよびアンチセンスsiRNAの相対位置を示す。8つの異なるアンチセンス鎖に従って8系統の二本鎖を用意した。siRNA配列と、突出ヌクレオチドの数を1塩基ずつ変化させた。
(A)32P(星印)キャップ標識センスおよびアンチセンス標的RNAと、siRNA二本鎖をグラフで示した図。センスおよびアンチセンス標的RNA切断の位置は、siRNA二本鎖の上方および下方に、それぞれ三角形で示す。
2塩基3’突出部(灰色のNN)は、表示したように配列および組成を改変した(T、2’−デオキシチミジン、dG、2’−デオキシグアノシン;星印、野生型siRNA二本鎖)。正規化した干渉比は、図11で記載したように決定した。野生型配列は図14に示したものと同じである。
1.1.実験手順
1.1.1 in vitro RNAi
以前記載されている(Tuschlら、1999;Zamoreら、2000)ように、in vitro RNAiおよび溶解物調製を実施した。最適なATP再生のためには、新しく溶解したクレアチンキナーゼ(Roche)を用いる必要がある。RNAi翻訳アッセイ(図1)は、5nMのdsRNA濃度と、25℃で15分の長いプレインキュベーション時間で実施した後、in vitro転写、キャッピングおよびポリアデニル化したPp−lucおよびRr−lucリポーターmRNAを添加した。インキュベーションを1時間継続した後、二重ルシフェラーゼアッセイ(Promega)およびモノライト3010Cルミノメーター(PharMingen)を用いて、Pp−lucおよびRr−lucタンパク質の相対量を分析した。
標準的手順を用いて、T7またはSP6プロモーター配列を有するPCR鋳型からのRNAのin vitro転写を実施した(例えば、Tuschlら、1998を参照)。Expedite RNAホスホルアミダイト(Proligo)を用いて、合成RNAを調製した。ジメトキシトリチル−1,4−ベンゼンジメタノール−スクシニル−アミノプロピル−CPGを用いて、3’アダプターオリゴヌクレオチドを合成した。オリゴリボヌクレオチドを、3mlの32%アンモニア/エタノール(3/1)において、55℃で4時間(Expedite RNA)または55℃で16時間かけて脱保護した(3’および5’アダプターDNA/RNAキメラオリゴヌクレオチド)後、以前記載されている(Tuschlら、1993)ように、脱シリル化してからゲル精製した。長い3’突出部を含むdsRNAを調製するためのRNA転写物は、センス方向にT7プロモーターを、アンチセンス方向にSP6プロモーターを含むPCR鋳型から作製した。5’プライマーとしてGCGTAATACGACTCACTATAGAACAATTGCTTTTACAG(下線部、T7プロモーター)と、3’プライマーとしてATTTAGGTGACACTATAGGCATAAAGAATTGAAGA(下線部、SP6プロモーター)、ならびに、鋳型として線状化Pp−lucプラスミド(pGEM−luc配列)(Tuschlら、1999)を用いて、センスおよびアンチセンス標的RNA用の転写鋳型をPCR増幅した。T7転写センスRNAは、177塩基長であり、開始コドンに対して位置113〜273のPp−luc配列と、これに続いて、3’末端にSP6プロモーター配列の17塩基の相補配列(complement)を含む。平滑末端dsRNA形成用の転写物は、単一のプロモーター配列だけを含む2つの異なるPCR産物からの転写によって調製した。
10nM dsRNAを15分プレインキュベートした後、10nMキャップ標識標的RNAをを添加することにより、標準RNAi反応を実施した。プロテイナーゼK処理(Tuschlら、1999)により、さらに2時間(図2A)または2.5時間(図5Bおよび6B)インキュベートした後、反応を停止した。次に、8または10%配列決定用ゲル上でサンプルを分析した。21および22塩基の合成RNA二本鎖を100nM最終濃度で用いた(図5B)。
標的RNAの不在下で、ショウジョウバエ溶解物における放射性標識dsRNAのインキュベーションにより(200μl反応物、1時間インキュベーション、50nM dsP111、または100nM dsP52もしくはdsP39)、21塩基のRNAを生成した。次に、反応混合物をプロテイナーゼKで処理した(Tuschlら、1999)後、dsRNAプロセシング産物を変性15%ポリアクリルアミドゲル上で分離した。少なくとも18〜24塩基のサイズ範囲を含むバンドを除去し、0.3M NaClに4℃で一晩かけて溶離した後、シリコン処理管に導入した。エタノール沈降によりRNAを回収した後、脱リン酸化した(30μl反応物、30分、50℃、10Uアルカリホスファターゼ、Roche)。フェノール/クロロホルム抽出により反応を停止し、RNAをエタノール沈降させた。次に、3’アダプターオリゴヌクレオチド(pUUUaaccgcatccttctcx:大文字はRNA;小文字はDNA;pはリン酸;xは4−ヒドロキシメチルベンジル)を脱リン酸化した約21塩基のRNAと連結させた(20μl反応物、30分、37℃、5μM 3’アダプター、50mM Tris−HCl、pH7.6、10mM MgCl2、0.2mM ATP、0.1mg/mlアセチル化BSA、15%DMSO、25U T4 RNAリガーゼ、Amersham-Pharmacia)(PanおよびUhlenbeck, 1992)。等量の8M尿素/50mM EDTA停止混合物(stopmix)の添加により連結反応を停止した後、15%ゲルに直接ロードした。連結収率は50%を超えた。連結産物をゲルから回収した後、5’−リン酸化した(20μl反応物、30分、37℃、2mM ATP、5U T4ポリヌクレオチドキナーゼ、NEB)。フェノール/クロロホルム抽出によりリン酸化反応を停止した後、エタノール沈降によりRNAを回収した。次に、前記と同様に、5’アダプター(tactaatacgactcactAAA:大文字はRNA;小文字はDNA)をリン酸化連結産物と連結させた。新しい連結産物をゲル精製し、キャリアとして用いる逆転写プライマー(GACTAGCTGGAATTCAAGGATGCGGTTAAA:太字はEcoRI部位)の存在下で、ゲル切片から溶離させた。逆転写(15μl反応物、30分、42℃、150U SuperscriptII逆転写酵素、Life Technologies)の後、5’プライマーCAGCCAACGGAATTCATACGACTCACTAAA(太字はEcoRI部位)と、3’RTプライマーを用いたPCRを実施した。PCR産物をフェノール/クロロホルム抽出により精製した後、エタノール沈降させた。次に、PCR産物をEcoRI(NEB)で消化してから、T4 DNAリガーゼ(高濃度、NEB)を用いてコンカテマー化する。サイズが200〜800bpの範囲にあるコンカテマーを低融点アガロースゲル上で分離し、標準的な融解およびフェノール抽出手順によりゲルから回収した後、エタノール沈降させた。非対合末端を標準的条件下でTaqポリメラーゼと一緒に72℃で15分インキュベートすることにより充填した後、TOPO TAクローニングキット(Invitrogen)を用いて、DNA産物をpCR2.1−TOPOベクターに直接連結した。PCRと、M13−20およびM13逆方向配列決定用プライマーを用いて、コロニーをスクリーニングした。カスタム(custom)配列決定(Sequence Laboratories Gottingen GmbH, ドイツ)のためにPCR産物を直接提出した。平均して、1クローン当たり4〜5個の21mer配列が得られた。
放射性標識し、ゲル精製したsiRNAおよび2D−TLCのヌクレアーゼP1消化を記載されている通りに実施した(Zamoreら、2000)。2μg/μlキャリアtRNAと30UリボヌクレアーゼT2(Life Technologies)を用いて、10mM酢酸アンモニウム(pH4.5)中、10μl反応物において、ヌクレアーゼT2消化を50℃で3時間実施した。非放射性標準の泳動をUVシャドウイング(shadowing)により測定した。ヌクレオシド−3’,5’−二リン酸の同一性は、γ−32P−ATPおよびT4ポリヌクレオチドキナーゼを用いた市販のヌクレオシド3’−一リン酸の5’−32Pリン酸化により調製した標準によるT2消化産物の同時泳動によって確認した(データは示していない)。
1.2.1 21および22塩基のRNA断片のプロセシングに必要な長さ
キイロショウジョウバエ合胞体胚から調製した溶解物は、in vitroにおいてRNAiを再現することから、RNAi機構の生化学的分析の新たなツールを提供するものである(Tuschlら、1999;Zamoreら、2000)。RNAiのためのdsRNAに必要な長さについてのin vitroおよびin vivo分析から、標的mRNAを分解する上で、短いdsRNA(<150bp)は、長いdsRNAより効果が低いことが明らかにされている(Caplenら、2000;Hammondら、2000;Ngoら、1998);Tuschlら、1999)。このmRNA分解効率が低い理由はわかっていない。従って、本発明者は、ショウジョウバエ溶解物における最適化条件下で(Zomoreら、2000)、標的RNA分解のためのdsRNAに必要な正確な長さを調べた。数系統のdsRNAを合成し、ホタルルシフェラーゼ(Pp−luc)リポーターRNAに対して指令させた。標的RNA発現の特異的抑制を二重ルシフェラーゼアッセイ(Tuschlら、1999)によりモニタリングした(図1Aおよび1B)。本発明者は、38bpという短いdsRNAの標的RNA発現の特異的阻害を検出したが、29〜36bpのdsRNAはこの過程において有効ではなかった。効果は、Pp−luc mRNAの標的位置および阻害度とは無関係で、dsRNAの長さと相関していた。すなわち、長鎖dsRNAの方が、短鎖dsRNAより有効であった。
ショウジョウバエ溶解物にdsRNAおよび5’−キャップ標識RNAを添加すると、標的RNAの配列特異的分解が起こる(Tuschlら、1999)。標的mRNAは、dsRNAと同一性のある領域内でしか切断されず、標的切断部位の多くは、21〜23塩基ずつ分離された(Zamoreら、2000)。従って、所与のdsRNAの切断部位の数は、dsRNAの長さを21で割った数とおおまかに対応することが予想された。本発明者は、キャップにおいて5’放射性標識されたセンスおよびアンチセンス標的RNA上の標的切断部位をマッピングした(Zamoreら、2000)(図3Aおよび3B)。配列決定用ゲル上で安定した5’切断産物を分離し、標的RNAからの部分的RNaseT1およびアルカリ性加水分解標準(ladder)との比較により、切断位置を決定した。
21〜23塩基のRNA断片を特性決定するために、RNA断片の5’および3’末端を調べた。ゲル精製した21〜23塩基のRNAを過ヨウ素酸化した後、β脱離すると、末端2’および3’ヒドロキシル基の存在が示された。21〜23merはまた、アルカリ性ホスファターゼ処理に応答性であり、これは5’末端リン酸基の存在を意味する。5’リン酸および3’ヒドロキシル末端の存在は、dsRNAが大腸菌RNaseIIIと類似した酵素活性によりプロセシングされ得ることを示唆している(確認のため、(Dunn, 1982;Nicholson, 1999;Robertson, 1990:Robertson, 1982)を参照)。
dsRNAプロセシングの産物の分析から、RNaseIII切断反応のあらゆる特徴を有する反応によって約21断片が生成されることがわかった(Dunn, 1982;Nicholson, 1999;Robertson, 1990;Robertson, 1982)。RNaseIIIは、dsRNAの両鎖に2つの付着切断を形成し、約2塩基の3’突出部を残す。本発明者は、クローン化した約21塩基断片のいくつかと配列が同じである21および22塩基のRNAを化学的に合成し、標的RNA分解を媒介する能力についてそれらを試験した(図5Aおよび5B)。21および22塩基のRNA二本鎖を、溶解物中100nMの濃度(52bpの対照dsRNAの10倍の濃度)でインキュベートした。これらの条件下で、標的RNA切断は容易に検出可能である。21および22塩基二本鎖の濃度を100から10nMまで下げても、やはり標的RNA切断が起こる。しかし、二本鎖の濃度を100から1,000nMに高めても、標的切断は増加しない。これは恐らく、溶解物内の制限タンパク質因子によるものであろう。
本発明者は、短い平滑末端dsRNAが、dsRNAの末端からプロセシングされることを明らかにした。RNAiにおけるdsRNAの長さ依存の研究中に、本発明者が、17〜20塩基の突出3’末端を有するdsRNAも分析したところ、驚くべきことに、これらが、平滑末端dsRNAより効力が弱いことがわかった。長い3’末端の阻害効果は、100bpまでのdsRNAに特に顕著であったが、これより長いdsRNAについてはそれほど強くなかった。未改変ゲル分析(データは示していない)によれば、この効果は、不完全なdsRNA形成によるものではなかった。本発明者は、長い突出3’末端の阻害効果を、短いRNA二本鎖の2つの末端の一方だけに対するdsRNAプロセシングを指令するツールとして使用できるかどうかを試験した。
新しい生化学データを用いて、どのようにしてdsRNAがmRNAをターゲッティングし、破壊するかについてのモデルを更新する(図7)。二本鎖RNAはまず、主に21および22塩基長で、かつ、RNaseIII様反応と類似した付着3’末端を有する短いRNA二本鎖にプロセシングされる(Dunn, 1982;Nicholson, 1999;Robertson, 1982)。プロセシングされたRNA断片の21〜23塩基長に基づき、RNaseIII様活性がRNAiに関与し得ることがすでに想定されていた(Bass, 2000)。この仮定は、RNaseIII反応産物に観察されるように、siRNAの末端に5’リン酸および3’ヒドロキシルが存在することにより支持される(Dunn, 1982;Nicholson, 1999)。細菌RNaseIII、S.セレビシエにおける真核生物相同体Rnt1p、およびS.ポンベにおけるPac1pは、リボソームRNA、ならびに、snRNAおよびsnoRNAのプロセシングにおいて機能することがわかっている(例えば、Chanfreauら、2000参照)。
2.1 方法
2.1.1 RNA調製
Expedite RNAホスホルアミダイトとチミジンホスホルアミダイト(Proligo, Germany)を用いて、21塩基のRNAを化学的に合成した。合成オリゴヌクレオチドを脱保護してからゲル精製した(実施例1)後、Sep−Pak C18カートリッジ(Waters, Milford, MA, USA)により精製を実施した(Tuschl, 1993)。siRNA配列がターゲッティングするGL2(アクセッション番号X65324)とGL3ルシフェラーゼ(アクセッション番号U47296)は、開始コドンの第1ヌクレオチドに対してコード領域153〜173と対応し、siRNAがターゲッティングするRL(アクセッション番号AF025846)は、開始コドン後の領域119〜129と対応した。より長いRNAは、PCR産物からT7RNAポリメラーゼで転写した後、ゲルおよびSep−Pak精製に付した。49および484bpのGL2またはGL3dsRNAは、翻訳の開始に対して、位置113〜161および113〜596にそれぞれ対応した。50および501bpのRL dsRNAは、位置118〜167および118〜618にそれぞれ対応した。ヒト化GFP(hG)をターゲッティングするdsRNA合成のためのPCR鋳型をpAD3から増幅した(Kehlenbach, 1998)ところ、50および501bpのhG dsRNAは、翻訳の開始に対して、位置118〜167および118〜618にそれぞれ対応した。
10%FBS、100単位/mlペニシリンおよび100μg/mlストレプトマイシンを補充したシュナイダーのショウジョウバエ培地(Life Technologies)において25℃で、S2細胞を増殖させた。10%FBS、100単位/mlペニシリンおよび100μg/mlストレプトマイシンを補充したダルベッコの改変イーグル培地において37℃で、293、NIH/3T3、HeLaS3、COS−7細胞を増殖させた。細胞を定期的に継代させて、対数増殖を維持した。約80%密集度でのトランスフェクションの24時間前に、哺乳動物細胞をトリプシン処理してから、抗生物質を含まない新鮮な培地で5倍に希釈した(1〜3×105細胞/ml)後、24ウェルプレート(500μl/ウェル)に移した。S2細胞はトリプシン処理せずに開裂反応に付した。付着細胞系について製造者が記載しているように、リポフェクトアミン2000試薬(Life Technologies)を用いて、トランスフェクションを実施した。1ウェルにつき、リポソームに組み込まれた1.0μgのpGL2−Control(Promega)またはpGL3−Control(Promega)、0.1μgのpRL−TK(Promega)および0.28μgのsiRNA二本鎖またはdsRNAを導入した;最終量は、1ウェル当たり600μlであった。トランスフェクションの後、細胞を20時間インキュベートしたが、その後の細胞は健常のようであった。次に、二重ルシフェラーゼアッセイ(Promega)で、ルシフェラーゼ発現をモニタリングした。1.1μgのhGFPコード化pAD3と0.28μgのinvGL2 inGL2 siRNAの共トランスフェクション後、哺乳動物細胞系の蛍光顕微鏡検査により、トランスフェクション効率を測定したところ、70〜90%であった。リポータープラスミドをXL−1 Blue(Stratagene)において増幅した後、Qiagenエンドフリー・マキシ・プラスミドキット(Qiagen EndoFree Maxi Plasmid Kit)を用いて精製した。
siRNAが、組織培養物においてもRNAiを媒介することができるか否かを試験するために、本発明者は、ウミシイタケ(Renilla reniformis)および、ホタルルシフェラーゼ(Photinus pyralis、GL2およびGL3)の2つの配列種をコードするリポーター遺伝子に対して指令される対称2塩基3’突出部を有する21塩基siRNA二本鎖を合成した(図8a、b)。カチオンリポソームを用いて、siRNA二本鎖をリポータープラスミドの組合せpGL2/pRLまたはpGL3/pRLと一緒に、キイロショウジョウバエ・シュナイダーS2細胞または哺乳動物細胞に共トランスフェクトした。トランスフェクションから20時間後にルシフェラーゼ活性を測定した。試験したすべての細胞系において、本発明者は、相同siRNA二本鎖(cognate siRNA duplex)の存在下でリポーター遺伝子の発現の特異的減弱を観察した(図9a〜j)。驚くことに、絶対ルシフェラーゼ発現レベルは、非相同siRNAによる影響を受けなかった。これは、21塩基のRNA二本鎖(例えば、HeLa細胞については図10a〜d)による有害な副作用がないことを意味している。キイロショウジョウバエS2細胞(図9a、b)において、ルシフェラーゼの特異的阻害は完全であった。リポーター遺伝子が50〜100倍強く発現した哺乳動物細胞では、特異的抑制は完全ではなかった(図9c〜j)。相同siRNAに応答して、GL2発現は、3〜12倍、GL3発現は9〜25倍、またRL発現は1〜3倍減弱した。293細胞については、RL siRNAによるRLルシフェラーゼのターゲッティングは無効であったが、GL2およびGL3標的は、特異的に応答した(図9i、j)。293細胞でRL発現の減弱がないのは、この発現が、試験した他の哺乳動物細胞系と比べて5〜20倍高いこと、および/またはRNA二次構造もしくは会合タンパク質のために標的配列の受容能力が制限されたことによるものであろう。それでも、相同siRNA二本鎖によるGL2およびGL3ルシフェラーゼの特異的ターゲッティングは、RNAiが293細胞においても機能していることを示している。
3.1 材料と方法
3.1.1 RNA調製とRNAiアッセイ
実施例1または2、あるいは、これまでの文献(Tuschlら、1999;Zamoreら、2000)に記載されているように、化学的RNA合成、アニーリング、およびルシフェラーゼに基づくRNAiアッセイを実施した。すべてのsiRNA二本鎖はホタルルシフェラーゼに対して指令され、ルシフェラーゼmRNA配列は、記載されている(Tuschlら、1999)ように、pGEM−luc(GenBankアクセッション番号X65316)由来のものであった。キイロショウジョウバエRNAi/翻訳反応において、siRNA二本鎖を15分インキュベートしてから、mRNAを添加した。翻訳に基づくRNAiアッセイを少なくとも3回繰り返して実施した。
3.2.1 21塩基のsiRNAの二本鎖における3’突出部の変動
前述のように、siRNA二本鎖の3’末端で2または3非対合ヌクレオチドは、それぞれの平滑末端二本鎖と比べて、標的RNA分解が効率的である。末端ヌクレオチドの機能のさらに総合的分析を実施するために、本発明者は、5つの21塩基センスsiRNA(各々、標的RNAに対する1塩基で表される)と、8つの21塩基アンチセンスsiRNA(各々、標的に対する1塩基で表される)を合成した(図11A)。センスおよびアンチセンスsiRNAを組み合わせることにより、7塩基3’突出部〜4塩基5’突出部の範囲にある合成突出末端を有する8系統のsiRNA二本鎖を作製した。二重ルシフェラーゼアッセイ系(Tuschlら、1999;Zamoreら、2000)を用いて、siRNA二本鎖の干渉を測定した。siRNA二本鎖は、ホタルルシフェラーゼmRNAに対して指令され、ウミシイタケルシフェラーゼmRNAを内部対照として用いた。siRNA二本鎖の存在下で、標的と対照ルシフェラーゼ活性のルミネセンス比を測定した後、dsRNAの不在下で得られた比に対して正規化した。比較のため、長いdsRNA(39〜504bp)の干渉比を図11Bに示す。長鎖dsRNA(図11A)については5nM、また、siRNA二本鎖(図11C〜J)については100nMの濃度で、干渉比を測定した。5nMの504bp dsRNAの完全なプロセシングにより、120nMの全siRNA二本鎖が得られたことから、siRNAについては100nM濃度を選択した。
RNAiに対するsiRNAの長さの影響を調べるために、本発明者は、3つの21塩基アンチセンス鎖と8つの18〜25塩基センス鎖とを組み合わせて、3系統のsiRNA二本鎖を作製した。アンチセンスsiRNAの3’突出部は、各siRNA二本鎖系統における1、2または3塩基に固定したのに対し、センスsiRNAは、その3’末端で変動させた(図12A)。センスsiRNAの長さとは無関係に、アンチセンスsiRNAの2塩基の3’突出部を有する二本鎖(図12C)は、1または3塩基の3’突出部を有するもの(図12B、D)より活性が高いことがわかった。アンチセンスsiRNAの1塩基の3’突出部を有する第1の系統では、センスsiRNAの1および2塩基の3’突出部をそれぞれ有する、21および22塩基センスsiRNAの二本鎖の活性が最も高かった。19〜25塩基のセンスsiRNAを有する二本鎖もRNAを媒介することができたが、程度は低かった。同様に、アンチセンスsiRNAの2塩基突出部を有する第2系統では、2塩基の3’突出部を有する21塩基のsiRNA二本鎖の活性が最も高く、18〜25塩基のセンスsiRNAとのその他すべての組合せは、有意な程度まで活性であった。3塩基のアンチセンスsiRNA3’突出部を有する最後の系統では、20塩基のセンスsiRNAおよび2塩基のセンス3’突出部を有する二本鎖だけが標的RNA発現を減弱することができた。以上、これらの結果から、siRNAの長さと共に、3’突出部の長さが重要であることと、2塩基3’突出部を有する21塩基のsiRNAの二本鎖がRNAiには最適であることがわかる。
次に、本発明者は、対称の2塩基3’突出部を維持しながら、両siRNA鎖の長さを同時に変化させて生じる影響を調べた(図13A)。図11Hの21塩基のsiRNA二本鎖を基準として含む2系統のsiRNA二本鎖を作製した。センスsiRNA(図13B)の3’末端またはアンチセンスsiRNA(図13C)の3’末端で塩基対合部分を延長することにより、二本鎖の長さを20〜25bpで変動させた。20〜23bpの二本鎖は、標的ルシフェラーゼ活性の特異的抑制を起こしたが、21塩基のsiRNA二本鎖は、他の二本鎖のどちらと比較しても少なくとも8倍有効であった。24および25塩基のsiRNA二本鎖は、検出可能な干渉を全く起こさなかった。配列特異的効果は、二本鎖の両末端における変動が同様の効果を生じたため、わずかであった。
RNAiにおけるsiRNAリボース残基の重要性を評価するため、2’−デオキシまたは2’−O−メチル修飾鎖を含む21塩基のsiRNAおよび2塩基3’突出部を有する二本鎖を試験した(図14)。2’−デオキシヌクレオチドによる2塩基3’突出部の置換では影響がなく、対合領域における突出部と隣接した2つの別のリボヌクレオチドの置換でも、有意に活性のsiRNAが生じた。従って、siRNA二本鎖の42塩基のうち8つをDNA残基で置換しても、活性は失われなかった。2’−デオキシ残基による一方または両方のsiRNA鎖の完全な置換では、2’−O−メチル残基による置換と同様に、RNAiを破壊した。
22塩基のsiRNA二本鎖および21塩基/22塩基の二本鎖について、標的RNA切断位置を事前に決定した。標的RNA切断の位置は、siRNA二本鎖が占める領域の中心部、すなわち、21または22塩基のsiRNAガイド配列と相補的な第1塩基から11または12塩基下流に位置することがわかった。2塩基3’突出部を有する5つの別個の21塩基siRNA二本鎖(図15A)を5’キャップ標識センスまたはアンチセンス標的RNAと一緒にキイロショウジョウバエ溶解物中でインキュベートした(Tuschlら、1999;Zamoreら、2000)。5’切断産物を配列決定用ゲル上で分離した(図15B)。切断されたセンス標的RNAの量は、翻訳に基づくアッセイで決定されるsiRNA二本鎖の効率と相関しており、siRNA二本鎖1、2および4(図15Bおよび11H、G、E)は、二本鎖3および5(図15Bおよび11F、D)より速く標的RNAを切断する。注目すべきことに、5’切断産物および投入標的RNAの放射活性の合計は、時間に関して一定ではなく、5’切断産物は蓄積しなかった。恐らく、5’−キャップのポリ(A)テイルのいずれかが欠如しているために、siRNA−エンドヌクレアーゼ複合体から放出した切断産物は急速に分解されるのであろう。
2塩基の3’突出部が、siRNA機能には好ましい。本発明者は、突出塩基の配列が、標的認識に寄与するのか、またはこの配列が、エンドヌクレアーゼ複合体(RISCまたはsiRNP)の認識に必要な特徴であるだけなのかを知ろうとした。本発明者は、AA、CC、GG、UUおよびUG3’突出部を有するセンスおよびアンチセンスsiRNAを合成し、2’−デオキシ修飾TdGおよびTTを含有させた。野生型siRNAは、センス3’突出部にAAを、また、アンチセンス3’突出部にUGを含んでいた(AA/UG)。siRNA二本鎖はすべて、干渉アッセイにおいて機能的であり、標的発現を少なくとも5倍減弱した(図17)。10倍以上標的発現を減弱した最も効率的なsiRNA二本鎖は、配列型:NN/UG、NN/UU、NN/TdG、およびNN/TT(Nは任意のヌクレオチドである)のものであった。AA、CCまたはGGのアンチセンスsiRNA3’突出部を有するsiRNA二本鎖は、野生型配列UGまたは突然変異配列UUと比較して、2〜4倍活性が低かった。RNAi効率が低いのは、恐らく、末端から2番目の3’塩基が配列特異的標識認識に寄与するためと考えられる。というのは、3’末端塩基は、GからUに改変しても、影響がないからである。
標的認識の配列特異性を調べるため、本発明者は、siRNA二本鎖の対合部分に配列改変を導入し、サイレンシングの効率を調べた。配列改変は、3または4塩基長の短い部分を逆転させるか、あるいは、点突然変異として導入した(図18)。一方のsiRNA鎖の配列改変は、相補的siRNA鎖において補償され、これによって、塩基対合したsiRNA二本鎖構造の不安定化(pertubing)を回避した。合成にかかるコストを下げるため、2塩基の3’突出部の配列は、すべてTT(T、2’−デオキシチミジン)とした。TT/TT基準siRNA二本鎖は、RNAiについて、野生型siRNA二本鎖AA/UGと同等であった(図17)。リポーターmRNA破壊を媒介する能力は、翻訳に基づくルミネセンスアッセイを用いて定量化した。逆転配列部分有するsiRNAの二本鎖は、ホタルルシフェラーゼリポーターをターゲッティングする能力が著しく低いことがわかった(図18)。アンチセンスsiRNAの3’末端と中央部との間に位置する配列改変は、標的RNA認識を完全に破壊したが、アンチセンスsiRNAの5’末端付近の突然変異は、わずかな程度のサイレンシングを呈示する。推定標的RNA切断部位の反対側に直接、または推定部位から1塩基離れて位置するA/U塩基対のトランスバージョンによって、標的RNA切断が阻止されるが、これは、siRNA二本鎖の中心部内の単一突然変異が、ミスマッチ標的を識別することを示している。
siRNAは、昆虫細胞だけではなく、哺乳動物細胞においても、遺伝子発現を不活性化するための有用な試薬であり、治療用途に極めて有望である。本発明者は、キイロショウジョウバエ胚溶解物において効率的な標的RNA分解を促進するのに必要なsiRNA二本鎖の構造上の決定因子を系統的に分析することにより、最も効力のあるsiRNA二本鎖の設計についての法則を提供した。完全なsiRNA二本鎖は、全RNAの同等量を用いれば、500bpのdsRNAと同等の効率で、遺伝子発現をサイレンシングすることができる。
効率的なサイレンシングsiRNA二本鎖は、21塩基のアンチセンスsiRNAから構成されるため、2塩基3’突出末端を有する19bp二重らせんを形成するように選択しなければならない。2塩基3’突出リボヌクレオチドの2’−デオキシ置換は、RNAiに影響を及ぼさないが、RNA合成にかかるコスト削減に役立ち、siRNA二本鎖のRNase抵抗を増強することができる。ところが、これより広範囲な2’−デオキシまたは2’−O−メチル修飾は、恐らく、siRNAP集合のためのタンパク質会合を妨害するために、siRNAがRNAiを媒介する能力を低下させる。
Claims (24)
- 少なくとも1つの修飾されたリボヌクレオチドを含む単離された二本鎖RNA分子を含む組成物であって、該RNA分子の各鎖が39〜52塩基長を有し、かつ、該RNA分子の第1の鎖が予め決定したmRNA標的分子に対して100%の同一性を有する配列を含み、該RNA分子の第2の鎖が該第1の鎖に完全に相補的であるか、または、連続する少なくとも39塩基にわたり該第1の鎖に相補的な配列を含み、ならびに、該修飾されたリボヌクレオチドがホスホロチオエート基を含む骨格鎖修飾リボヌクレオチドであることを特徴とする、該RNA分子が、2塩基の3'突出部を含む21〜23塩基長の1以上の二本鎖断片にプロセシングされて、標的特異的なRNA干渉を引き起こすための、上記組成物。
- 二本鎖RNA分子の各鎖が39塩基長を有する、請求項1に記載の組成物。
- 下記のステップを含む、請求項1または2に記載の二本鎖RNA分子を含む組成物の作製方法:
(a)各々が39〜52塩基長を有する2本のRNA鎖を合成するステップであって、該RNA鎖は二本鎖RNA分子を形成することができるものである、上記ステップ、および
(b)二本鎖RNA分子が形成される条件下で合成RNA鎖を結合させるステップであって、得られる二本鎖RNA分子は標的特異的なRNA干渉が可能なものである、上記ステップ。 - RNA鎖が化学的に合成される、請求項3に記載の方法。
- RNA鎖が酵素により合成される、請求項3に記載の方法。
- 下記のステップを含む、in vitroで動物細胞において標的特異的なRNA干渉を媒介する方法:
(a)標的特異的なRNA干渉を起こすことができる条件下で、上記細胞を請求項1または2に記載の組成物の二本鎖RNA分子と接触させるステップ、および
(b)上記二本鎖RNAと同一の配列部分を有する標的核酸に対する、上記二本鎖RNAにより引き起こされる標的特異的なRNA干渉を媒介するステップ。 - 接触ステップ(a)が、標的特異的なRNA干渉を起こすことができる標的細胞内に、二本鎖RNA分子を導入するステップを含む、請求項6に記載の方法。
- 導入ステップが、キャリア媒介による送達または注射を含む、請求項7に記載の方法。
- in vitroで動物細胞における遺伝子の機能を決定するための、請求項6〜8のいずれか1項に記載の方法の使用。
- in vitroで動物細胞における遺伝子の機能を抑制するための、請求項6〜8のいずれか1項に記載の方法の使用。
- 遺伝子が病理的状態と関連する、請求項9または10に記載の使用。
- 遺伝子が病原体関連遺伝子である、請求項11に記載の使用。
- 遺伝子がウイルス遺伝子である、請求項12に記載の使用。
- 遺伝子が腫瘍関連遺伝子である、請求項11に記載の使用。
- 遺伝子が自己免疫疾患関連遺伝子である、請求項11に記載の使用。
- 下記のステップを含む、標的遺伝子特異的ノックアウト表現型を示す動物細胞の作製方法:
(a)該細胞に対して、内因性標的遺伝子の発現を阻害しうる少なくとも1つの二本鎖RNA分子によって、トランスフェクトするステップであって、該二本鎖RNA分子の各RNA鎖が39〜52塩基長を有し、かつ、互いに完全に相補的であるか、または、連続する少なくとも39塩基にわたり相補的な配列を含み、さらに、該二本鎖RNA分子が少なくとも1つのホスホロチオエート基を含む骨格鎖修飾リボヌクレオチドを含む、ステップ、
(b)上記(a)のステップでトランスフェクトした該細胞において、該二本鎖RNA分子が、標的特異的なRNA干渉が可能な1以上の二本鎖断片にプロセシングされるステップであって、該二本鎖断片の少なくとも一方の鎖が1〜3塩基の3’突出部を有する21〜23塩基長の断片であり、および、3’突出部を除く該二本鎖断片の一方の鎖が、予め決定されたmRNA標的分子に対して100%の同一性を有する配列からなる、ステップ、ならびに、
(c)上記(b)のステップでプロセシングされた該二本鎖断片によって該細胞の内因性遺伝子の発現を阻害するステップ。 - 動物細胞が、哺乳動物細胞である、請求項16に記載の方法。
- 哺乳動物細胞が、ヒト細胞である、請求項17に記載の方法。
- 動物細胞が、遺伝子発現プロフィールを分析するための、または、プロテオーム分析のためのものである、請求項16〜18のいずれか1項に記載の方法。
- 分析が、機能および/または表現型の分析を含む、請求項19に記載の方法。
- 動物細胞が、調製手法のためのものである、請求項16〜18のいずれか1項に記載の方法。
- 調製手法が、真核細胞からタンパク質またはタンパク質複合体を単離するためのものである、請求項21に記載の方法。
- 調製手法が、高分子量タンパク質複合体を単離するためのものである、請求項22に記載の方法。
- 高分子量タンパク質複合体が核酸を含む、請求項23に記載の方法。
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Families Citing this family (1209)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0642589A4 (en) * | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
US20030206887A1 (en) * | 1992-05-14 | 2003-11-06 | David Morrissey | RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) |
US5639647A (en) * | 1994-03-29 | 1997-06-17 | Ribozyme Pharmaceuticals, Inc. | 2'-deoxy-2'alkylnucleotide containing nucleic acid |
US9096636B2 (en) | 1996-06-06 | 2015-08-04 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds and their use in gene modulation |
US7812149B2 (en) | 1996-06-06 | 2010-10-12 | Isis Pharmaceuticals, Inc. | 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations |
US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20040219569A1 (en) * | 1999-07-06 | 2004-11-04 | Fruma Yehiely | Gene identification method |
US20110003879A1 (en) * | 2005-03-11 | 2011-01-06 | Vincent Mark D | Antisense oligonucleotides targeted to the coding region of thymidylate synthase and uses thereof |
CN101818145A (zh) | 1998-03-20 | 2010-09-01 | 联邦科学和工业研究组织 | 控制基因表达 |
AUPP249298A0 (en) | 1998-03-20 | 1998-04-23 | Ag-Gene Australia Limited | Synthetic genes and genetic constructs comprising same I |
EP1071753A2 (en) * | 1998-04-20 | 2001-01-31 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid molecules with novel chemical compositions capable of modulating gene expression |
EP1147204A1 (en) | 1999-01-28 | 2001-10-24 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
DE19956568A1 (de) | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
US7601494B2 (en) | 1999-03-17 | 2009-10-13 | The University Of North Carolina At Chapel Hill | Method of screening candidate compounds for susceptibility to biliary excretion |
ES2568899T3 (es) | 1999-04-09 | 2016-05-05 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de una molécula inmunofuncional |
US6656698B1 (en) * | 1999-06-30 | 2003-12-02 | Millennium Pharmaceuticals, Inc. | 12832, a novel human kinase-like molecule and uses thereof |
US6423885B1 (en) | 1999-08-13 | 2002-07-23 | Commonwealth Scientific And Industrial Research Organization (Csiro) | Methods for obtaining modified phenotypes in plant cells |
US8128922B2 (en) * | 1999-10-20 | 2012-03-06 | Johns Hopkins University | Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen |
GB9925459D0 (en) * | 1999-10-27 | 1999-12-29 | Plant Bioscience Ltd | Gene silencing |
DE10100586C1 (de) | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
DE10160151A1 (de) * | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
US7829693B2 (en) * | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US7179796B2 (en) | 2000-01-18 | 2007-02-20 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTP1B expression |
US8273866B2 (en) * | 2002-02-20 | 2012-09-25 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA) |
WO2005019453A2 (en) * | 2001-05-18 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA) |
US8202979B2 (en) * | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
WO2002081628A2 (en) * | 2001-04-05 | 2002-10-17 | Ribozyme Pharmaceuticals, Incorporated | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies |
US20080039414A1 (en) * | 2002-02-20 | 2008-02-14 | Sima Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US20050032733A1 (en) * | 2001-05-18 | 2005-02-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA) |
US20030084471A1 (en) * | 2000-03-16 | 2003-05-01 | David Beach | Methods and compositions for RNA interference |
US8202846B2 (en) | 2000-03-16 | 2012-06-19 | Cold Spring Harbor Laboratory | Methods and compositions for RNA interference |
IL151781A0 (en) | 2000-03-16 | 2003-04-10 | Genetica Inc | Methods and compositions for rna interference |
WO2001075164A2 (en) * | 2000-03-30 | 2001-10-11 | Whitehead Institute For Biomedical Research | Rna sequence-specific mediators of rna interference |
PT2360253E (pt) * | 2000-03-30 | 2014-05-29 | Max Planck Ges Zur Förderung Der Wissenschaften E V | Métodos de produção de células ou organismos knockdown através de interferência por rna com mediadores de rna específicos de sequência e usos dos mesmos |
US7662791B2 (en) | 2000-08-02 | 2010-02-16 | University Of Southern California | Gene silencing using mRNA-cDNA hybrids |
US20080242627A1 (en) * | 2000-08-02 | 2008-10-02 | University Of Southern California | Novel rna interference methods using dna-rna duplex constructs |
WO2002012281A2 (en) * | 2000-08-03 | 2002-02-14 | Johns Hopkins University | Molecular vaccine linking an endoplasmic reticulum chaperone polypeptide to an antigen |
US20080032942A1 (en) | 2000-08-30 | 2008-02-07 | Mcswiggen James | RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (siNA) |
US20030190635A1 (en) * | 2002-02-20 | 2003-10-09 | Mcswiggen James A. | RNA interference mediated treatment of Alzheimer's disease using short interfering RNA |
WO2009042910A2 (en) * | 2007-09-26 | 2009-04-02 | University Of South Florida | Ship inhibition to direct hematopoietic stem cells and induce extramedullary hematopoiesis |
US7691821B2 (en) * | 2001-09-19 | 2010-04-06 | University Of South Florida | Inhibition of SHIP to enhance stem cell harvest and transplantation |
US20020165192A1 (en) | 2000-09-19 | 2002-11-07 | Kerr William G. | Control of NK cell function and survival by modulation of ship activity |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
DK2813582T3 (en) | 2000-12-01 | 2017-07-31 | Max-Planck-Gesellschaft Zur Förderung Der Wss E V | Small RNA molecules that mediate RNA interference |
US8546143B2 (en) | 2001-01-09 | 2013-10-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
US7767802B2 (en) | 2001-01-09 | 2010-08-03 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
EP1229134A3 (en) * | 2001-01-31 | 2004-01-28 | Nucleonics, Inc | Use of post-transcriptional gene silencing for identifying nucleic acid sequences that modulate the function of a cell |
US20060211642A1 (en) * | 2001-05-18 | 2006-09-21 | Sirna Therapeutics, Inc. | RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA) |
US20050233997A1 (en) * | 2001-05-18 | 2005-10-20 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA) |
US20050014172A1 (en) | 2002-02-20 | 2005-01-20 | Ivan Richards | RNA interference mediated inhibition of muscarinic cholinergic receptor gene expression using short interfering nucleic acid (siNA) |
US20070093437A1 (en) * | 2001-05-18 | 2007-04-26 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of xiap gene expression using short interfering nucleic acid (sina) |
US20050182007A1 (en) * | 2001-05-18 | 2005-08-18 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA) |
US20080188430A1 (en) * | 2001-05-18 | 2008-08-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA) |
US20040198682A1 (en) * | 2001-11-30 | 2004-10-07 | Mcswiggen James | RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (siNA) |
US9994853B2 (en) | 2001-05-18 | 2018-06-12 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
US20050054596A1 (en) * | 2001-11-30 | 2005-03-10 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20050287128A1 (en) * | 2001-05-18 | 2005-12-29 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of TGF-beta and TGF-beta receptor gene expression using short interfering nucleic acid (siNA) |
US20050164967A1 (en) * | 2001-05-18 | 2005-07-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA) |
US20060142225A1 (en) * | 2001-05-18 | 2006-06-29 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of cyclin dependent kinase-2 (CDK2) gene expression using short interfering nucleic acid (siNA) |
US20050158735A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proliferating cell nuclear antigen (PCNA) gene expression using short interfering nucleic acid (siNA) |
US20050164224A1 (en) * | 2001-05-18 | 2005-07-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA) |
US20050159381A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of chromosome translocation gene expression using short interfering nucleic acid (siNA) |
US20050159382A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA) |
US20050176663A1 (en) * | 2001-05-18 | 2005-08-11 | Sima Therapeutics, Inc. | RNA interference mediated inhibition of protein tyrosine phosphatase type IVA (PRL3) gene expression using short interfering nucleic acid (siNA) |
US20050159379A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc | RNA interference mediated inhibition of gastric inhibitory polypeptide (GIP) and gastric inhibitory polypeptide receptor (GIPR) gene expression using short interfering nucleic acid (siNA) |
US20050203040A1 (en) * | 2001-05-18 | 2005-09-15 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA) |
US20050159380A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of angiopoietin gene expression using short interfering nucleic acid (siNA) |
US20050187174A1 (en) * | 2001-05-18 | 2005-08-25 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
US20070042983A1 (en) * | 2001-05-18 | 2007-02-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
US20050164968A1 (en) * | 2001-05-18 | 2005-07-28 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of ADAM33 gene expression using short interfering nucleic acid (siNA) |
US20050261219A1 (en) * | 2001-05-18 | 2005-11-24 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA) |
US20050176025A1 (en) * | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA) |
US20050159378A1 (en) * | 2001-05-18 | 2005-07-21 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA) |
US20050196765A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of checkpoint Kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA) |
US20050196767A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA) |
US20050196781A1 (en) * | 2001-05-18 | 2005-09-08 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of STAT3 gene expression using short interfering nucleic acid (siNA) |
US20050143333A1 (en) * | 2001-05-18 | 2005-06-30 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (SINA) |
US20050137155A1 (en) * | 2001-05-18 | 2005-06-23 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (siNA) |
US20050288242A1 (en) * | 2001-05-18 | 2005-12-29 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA) |
US20050233344A1 (en) * | 2001-05-18 | 2005-10-20 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of platelet derived growth factor (PDGF) and platelet derived growth factor receptor (PDGFR) gene expression using short interfering nucleic acid (siNA) |
US20050153914A1 (en) * | 2001-05-18 | 2005-07-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of MDR P-glycoprotein gene expression using short interfering nucleic acid (siNA) |
US20050176024A1 (en) * | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of epidermal growth factor receptor (EGFR) gene expression using short interfering nucleic acid (siNA) |
US20050176664A1 (en) * | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of cholinergic muscarinic receptor (CHRM3) gene expression using short interfering nucleic acid (siNA) |
US20050079610A1 (en) * | 2001-05-18 | 2005-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA) |
US20050267058A1 (en) * | 2001-05-18 | 2005-12-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (sINA) |
US20050136436A1 (en) * | 2001-05-18 | 2005-06-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of G72 and D-amino acid oxidase (DAAO) gene expression using short interfering nucleic acid (siNA) |
US20030175950A1 (en) * | 2001-05-29 | 2003-09-18 | Mcswiggen James A. | RNA interference mediated inhibition of HIV gene expression using short interfering RNA |
US20050124569A1 (en) * | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA) |
US20080161256A1 (en) * | 2001-05-18 | 2008-07-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
US20050119212A1 (en) * | 2001-05-18 | 2005-06-02 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of FAS and FASL gene expression using short interfering nucleic acid (siNA) |
US20050148530A1 (en) | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20050191618A1 (en) * | 2001-05-18 | 2005-09-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA) |
WO2005014811A2 (en) * | 2003-08-08 | 2005-02-17 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF XIAP GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US20050256068A1 (en) | 2001-05-18 | 2005-11-17 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of stearoyl-CoA desaturase (SCD) gene expression using short interfering nucleic acid (siNA) |
US20050176666A1 (en) * | 2001-05-18 | 2005-08-11 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of GPRA and AAA1 gene expression using short interfering nucleic acid (siNA) |
US20050048529A1 (en) * | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
US20050209180A1 (en) * | 2001-05-18 | 2005-09-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA) |
US20040219671A1 (en) * | 2002-02-20 | 2004-11-04 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of parkinson disease using short interfering nucleic acid (siNA) |
US20050124566A1 (en) * | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of myostatin gene expression using short interfering nucleic acid (siNA) |
US20070270579A1 (en) * | 2001-05-18 | 2007-11-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
US20050282188A1 (en) * | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
US20050233996A1 (en) * | 2002-02-20 | 2005-10-20 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hairless (HR) gene expression using short interfering nucleic acid (siNA) |
US20050222066A1 (en) * | 2001-05-18 | 2005-10-06 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US7109165B2 (en) * | 2001-05-18 | 2006-09-19 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
US20050239731A1 (en) * | 2001-05-18 | 2005-10-27 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of MAP kinase gene expression using short interfering nucleic acid (siNA) |
US7517864B2 (en) | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20040019001A1 (en) * | 2002-02-20 | 2004-01-29 | Mcswiggen James A. | RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA |
US20090299045A1 (en) * | 2001-05-18 | 2009-12-03 | Sirna Therapeutics, Inc. | RNA Interference Mediated Inhibition Of Interleukin and Interleukin Gene Expression Using Short Interfering Nucleic Acid (siNA) |
US20060148743A1 (en) * | 2001-05-18 | 2006-07-06 | Vasant Jadhav | RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA) |
EP1390472A4 (en) * | 2001-05-29 | 2004-11-17 | Sirna Therapeutics Inc | NUCLEIC ACID TREATMENT OF DISEASES OR SIDES RELATED TO RAS, HER2 AND HIV LEVELS |
US8008472B2 (en) | 2001-05-29 | 2011-08-30 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of human immunodeficiency virus (HIV) gene expression using short interfering nucleic acid (siNA) |
US20050019915A1 (en) | 2001-06-21 | 2005-01-27 | Bennett C. Frank | Antisense modulation of superoxide dismutase 1, soluble expression |
CA2451643C (en) | 2001-06-21 | 2012-11-13 | Isis Pharmaceuticals, Inc. | Antisense modulation of superoxide dismutase 1, soluble expression |
DE10133858A1 (de) * | 2001-07-12 | 2003-02-06 | Aventis Pharma Gmbh | Synthetische doppelsträngige Oligonucleotide zur gezielten Hemmung der Genexpression |
JP4210737B2 (ja) | 2001-07-12 | 2009-01-21 | ユニバーシティー オブ マサチューセッツ | 遺伝子サイレンシングを仲介する低分子干渉リボ核酸のインビボにおける製造方法 |
PT2280070E (pt) * | 2001-07-23 | 2015-10-29 | Univ Leland Stanford Junior | Métodos e composições para inibição mediada por iarn da expressão génica em mamíferos |
US10590418B2 (en) * | 2001-07-23 | 2020-03-17 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for RNAi mediated inhibition of gene expression in mammals |
US20090247606A1 (en) * | 2001-08-28 | 2009-10-01 | Sirna Therapeutics, Inc. | RNA Interference Mediated Inhibition of Adenosine A1 Receptor (ADORA1) Gene Expression Using Short Interfering Nucleic Acid (siNA) |
US20030198627A1 (en) * | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
DE10163098B4 (de) * | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
US7745418B2 (en) | 2001-10-12 | 2010-06-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting viral replication |
US20050119202A1 (en) * | 2001-10-26 | 2005-06-02 | Roland Kreutzer | Medicament to treat a fibrotic disease |
CN1604783A (zh) * | 2001-10-26 | 2005-04-06 | 里伯药品公司 | 通过rna干扰治疗纤维化疾病的药物 |
DE10230996A1 (de) * | 2001-10-26 | 2003-07-17 | Ribopharma Ag | Medikament zur Behandlung eines Pankreaskarzinoms |
WO2003035870A1 (de) * | 2001-10-26 | 2003-05-01 | Ribopharma Ag | Medikament zur behandlung eines pankreaskarzinoms |
WO2003040399A2 (en) * | 2001-11-02 | 2003-05-15 | Intradigm Corporation | Therapeutic methods for nucleic acid delivery vehicles |
US20040063654A1 (en) * | 2001-11-02 | 2004-04-01 | Davis Mark E. | Methods and compositions for therapeutic use of RNA interference |
CA2465860A1 (en) * | 2001-11-02 | 2004-04-22 | Insert Therapeutics, Inc. | Methods and compositions for therapeutic use of rna interference |
EP1445312B1 (en) * | 2001-11-21 | 2012-12-26 | Astellas Pharma Inc. | Method of inhibiting gene expression |
US20040138163A1 (en) * | 2002-05-29 | 2004-07-15 | Mcswiggen James | RNA interference mediated inhibition of vascular edothelial growth factor and vascular edothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20050075304A1 (en) * | 2001-11-30 | 2005-04-07 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US20070203333A1 (en) * | 2001-11-30 | 2007-08-30 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
US7294504B1 (en) | 2001-12-27 | 2007-11-13 | Allele Biotechnology & Pharmaceuticals, Inc. | Methods and compositions for DNA mediated gene silencing |
WO2003062421A1 (en) * | 2002-01-17 | 2003-07-31 | The University Of British Columbia | Bispecific antisense olignucleotides that inhibit igfbp-2 and igfbp-5 and methods of using same |
DE10202419A1 (de) | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
GB0201477D0 (en) * | 2002-01-23 | 2002-03-13 | Novartis Forschungsstiftung | Methods of obtaining isoform specific expression in mammalian cells |
CA2474910A1 (en) * | 2002-02-01 | 2003-08-07 | Sequitur, Inc. | Oligonucleotide compositions with enhanced efficiency |
US20060009409A1 (en) * | 2002-02-01 | 2006-01-12 | Woolf Tod M | Double-stranded oligonucleotides |
EP1572902B1 (en) * | 2002-02-01 | 2014-06-11 | Life Technologies Corporation | HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES |
US20050096289A1 (en) * | 2002-02-07 | 2005-05-05 | Hans Prydz | Methods and compositions for modulating tissue factor |
IL163547A0 (en) * | 2002-02-12 | 2005-12-18 | Quark Biotech Inc | Use of the axl receptor for diagnosis and treatment of renal disease |
EP1474512A2 (en) * | 2002-02-13 | 2004-11-10 | Axordia Limited | Method to modify differentiation of pluripotential stem cells |
CA2476530A1 (en) | 2002-02-14 | 2003-08-21 | City Of Hope | Methods for producing interfering rna molecules in mammalian cells and therapeutic uses for such molecules |
US7928220B2 (en) | 2002-02-20 | 2011-04-19 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA) |
US8013143B2 (en) | 2002-02-20 | 2011-09-06 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA) |
US20090247613A1 (en) * | 2002-02-20 | 2009-10-01 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF B-CELL CLL/LYMPHOMA-2 (BCL2) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US7691999B2 (en) | 2002-02-20 | 2010-04-06 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of NOGO and NOGO receptor gene expression using short interfering nucleic acid (siNA) |
JP2005517423A (ja) * | 2002-02-20 | 2005-06-16 | サーナ・セラピューティクス・インコーポレイテッド | 短干渉核酸(siNA)を用いるTGF−ベータおよびTGF−ベータレセプター遺伝子の発現のRNA干渉媒介性阻害 |
WO2003106476A1 (en) * | 2002-02-20 | 2003-12-24 | Sirna Therapeutics, Inc | Nucleic acid mediated inhibition of enterococcus infection and cytolysin toxin activity |
EP1495041A4 (en) * | 2002-02-20 | 2006-02-01 | Sirna Therapeutics Inc | RNA interferon-mediated inhibition of gene expression of G72 and D-amino acid oxidase (DAAO) using short-term interfering nucleic acid (siNA) |
US20090253774A1 (en) | 2002-02-20 | 2009-10-08 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET DERIVED GROWTH FACTOR (PDGF) AND PLATELET DERIVED GROWTH FACTOR RECEPTOR (PDGFR) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
CA2457528C (en) | 2002-02-20 | 2011-07-12 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of hepatitis c virus (hcv) gene expression using short interfering nucleic acid (sina) |
US20090137509A1 (en) * | 2002-02-20 | 2009-05-28 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF PROLIFERATION CELL NUCLEAR ANTIGEN (PCNA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US7795422B2 (en) | 2002-02-20 | 2010-09-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of hypoxia inducible factor 1 (HIF1) gene expression using short interfering nucleic acid (siNA) |
US20090192105A1 (en) | 2002-02-20 | 2009-07-30 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF INTERCELLULAR ADHESION MOLECULE (ICAM) GENE EXPRESSION USING SHORT INTERFERING NUCELIC ACID (siNA) |
EP1432724A4 (en) | 2002-02-20 | 2006-02-01 | Sirna Therapeutics Inc | RNA inhibition mediated inhibition of MAP KINASE GENES |
US9657294B2 (en) | 2002-02-20 | 2017-05-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US20100240730A1 (en) * | 2002-02-20 | 2010-09-23 | Merck Sharp And Dohme Corp. | RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA) |
US7662952B2 (en) | 2002-02-20 | 2010-02-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acid (siNA) |
US9181551B2 (en) | 2002-02-20 | 2015-11-10 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US20050096284A1 (en) * | 2002-02-20 | 2005-05-05 | Sirna Therapeutics, Inc. | RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA) |
US7678897B2 (en) | 2002-02-20 | 2010-03-16 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of platelet-derived endothelial cell growth factor (ECGF1) gene expression using short interfering nucleic acid (siNA) |
US7897753B2 (en) | 2002-02-20 | 2011-03-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of XIAP gene expression using short interfering nucleic acid (siNA) |
AU2003211058A1 (en) * | 2002-02-20 | 2003-09-09 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED TARGET DISCOVERY AND TARGET VALIDATION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US8258288B2 (en) | 2002-02-20 | 2012-09-04 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of respiratory syncytial virus (RSV) expression using short interfering nucleic acid (siNA) |
US7683166B2 (en) * | 2002-02-20 | 2010-03-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA) |
US7910724B2 (en) * | 2002-02-20 | 2011-03-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of Fos gene expression using short interfering nucleic acid (siNA) |
US8232383B2 (en) * | 2002-02-20 | 2012-07-31 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US7893248B2 (en) | 2002-02-20 | 2011-02-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of Myc and/or Myb gene expression using short interfering nucleic acid (siNA) |
US7667029B2 (en) | 2002-02-20 | 2010-02-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of checkpoint kinase-1 (CHK-1) gene expression using short interfering nucleic acid (siNA) |
US20090093439A1 (en) * | 2002-02-20 | 2009-04-09 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF CHROMOSOME TRANSLOCATION GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US7928218B2 (en) * | 2002-02-20 | 2011-04-19 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of polycomb group protein EZH2 gene expression using short interfering nucleic acid (siNA) |
US7897757B2 (en) * | 2002-02-20 | 2011-03-01 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of protein tyrosine phosphatase-1B (PTP-1B) gene expression using short interfering nucleic acid (siNA) |
US7897752B2 (en) | 2002-02-20 | 2011-03-01 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of telomerase gene expression using short interfering nucleic acid (siNA) |
US20090253773A1 (en) | 2002-02-20 | 2009-10-08 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF TNF AND TNF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US7700760B2 (en) | 2002-02-20 | 2010-04-20 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular cell adhesion molecule (VCAM) gene expression using short interfering nucleic acid (siNA) |
EP1478730A4 (en) * | 2002-02-20 | 2006-01-25 | Sirna Therapeutics Inc | INTERFERENCE RNA-INDUCED INHIBITION OF THE GENE EXPRESSION OF SUPERFAMILY TFN AND TFN RECEPTOR SUPERFAMILY USING SHORT INTERFERENCE NUCLEIC ACID (SINA) |
US7928219B2 (en) | 2002-02-20 | 2011-04-19 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (SINA) |
JP2005517437A (ja) * | 2002-02-20 | 2005-06-16 | サーナ・セラピューティクス・インコーポレイテッド | 短干渉核酸(siNa)を用いる表皮成長因子レセプター遺伝子発現のRNA干渉媒介性阻害 |
US7667030B2 (en) | 2002-02-20 | 2010-02-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA) |
US20090099117A1 (en) | 2002-02-20 | 2009-04-16 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF MYOSTATIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US8067575B2 (en) | 2002-02-20 | 2011-11-29 | Merck, Sharp & Dohme Corp. | RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA) |
US20090306182A1 (en) * | 2002-02-20 | 2009-12-10 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF MAP KINASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
AU2003213005A1 (en) * | 2002-02-20 | 2003-09-09 | Sirna Therapeutics, Inc | RNA INTERFERENCE MEDIATED INHIBITION OF PROTEIN KINASE C ALPHA (PKC-ALPHA) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US20090233983A1 (en) * | 2002-02-20 | 2009-09-17 | Sirna Therapeutics Inc. | RNA Interference Mediated Inhibition of Protein Tyrosine Phosphatase-1B (PTP-1B) Gene Expression Using Short Interfering RNA |
US7683165B2 (en) | 2002-02-20 | 2010-03-23 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA) |
US7935812B2 (en) | 2002-02-20 | 2011-05-03 | Merck Sharp & Dohme Corp. | RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA) |
WO2003072745A2 (en) * | 2002-02-22 | 2003-09-04 | Eshleman James R | Antigene locks and therapeutic uses thereof |
EP1575481A4 (en) * | 2002-03-01 | 2010-01-06 | Celltech R & D Inc | PROCESS FOR INCREASING OR REDUCING THE BONE DENSITY |
WO2003076592A2 (en) * | 2002-03-06 | 2003-09-18 | Rigel Pharmaceuticals, Inc. | Novel method for delivery and intracellular synthesis of sirna molecules |
US7274703B2 (en) * | 2002-03-11 | 2007-09-25 | 3Com Corporation | Stackable network units with resiliency facility |
AU2003224725A1 (en) * | 2002-03-20 | 2003-10-08 | Brigham And Women's Hospital, Inc. | Hiv therapeutic |
US7357928B2 (en) | 2002-04-08 | 2008-04-15 | University Of Louisville Research Foundation, Inc. | Method for the diagnosis and prognosis of malignant diseases |
JP2006500910A (ja) * | 2002-04-18 | 2006-01-12 | アキュイティ ファーマシューティカルズ、インク. | Cnsと眼の標的遺伝子を特異的に調節するための手段と方法及びその同定法 |
CA2524569C (en) | 2002-05-03 | 2013-10-22 | Duke University | A method of regulating gene expression |
US7199107B2 (en) * | 2002-05-23 | 2007-04-03 | Isis Pharmaceuticals, Inc. | Antisense modulation of kinesin-like 1 expression |
AU2003283951A1 (en) | 2002-05-23 | 2004-03-03 | Ceptyr, Inc. | Modulation of biological signal transduction by rna interference |
AU2003237686A1 (en) * | 2002-05-24 | 2003-12-12 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna interference mediating small rna molecules |
US20040248094A1 (en) * | 2002-06-12 | 2004-12-09 | Ford Lance P. | Methods and compositions relating to labeled RNA molecules that reduce gene expression |
AU2003276666A1 (en) * | 2002-06-12 | 2003-12-31 | Ambion, Inc. | Methods and compositions relating to polypeptides with rnase iii domains that mediate rna interference |
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 |
EP1513538A4 (en) * | 2002-06-14 | 2007-08-22 | Mirus Bio Corp | Novel methods for introducing polynucleotides into cells |
AU2003243094B2 (en) * | 2002-06-21 | 2007-08-30 | Sinogenomax Company Ltd. | Randomised DNA libraries and double-stranded RNA libraries, use and method of production thereof |
CA2491034A1 (en) * | 2002-06-26 | 2004-01-08 | The Penn State Research Foundation | Methods and materials for treating human papillomavirus infections |
AU2003245160B2 (en) | 2002-06-28 | 2009-09-24 | Arbutus Biopharma Corporation | Method and apparatus for producing liposomes |
AU2003254334A1 (en) | 2002-07-10 | 2004-02-02 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna-interference by single-stranded rna molecules |
US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
DK1527176T4 (en) | 2002-08-05 | 2017-07-03 | Silence Therapeutics Gmbh | ADDITIONAL NEW FORMS OF INTERFERRING RNA MOLECULES |
AU2015264957B2 (en) * | 2002-08-05 | 2017-10-26 | Silence Therapeutics Gmbh | Further novel forms of interfering rna molecules |
US20040241854A1 (en) | 2002-08-05 | 2004-12-02 | Davidson Beverly L. | siRNA-mediated gene silencing |
US20080274989A1 (en) | 2002-08-05 | 2008-11-06 | University Of Iowa Research Foundation | Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof |
DK1389637T3 (da) | 2002-08-05 | 2012-09-03 | Silence Therapeutics Ag | Interfererende RNA-molekyler med stumpe ender |
AU2012216354B2 (en) * | 2002-08-05 | 2016-01-14 | Silence Therapeutics Gmbh | Further novel forms of interfering RNA molecules |
KR20120029002A (ko) * | 2002-08-05 | 2012-03-23 | 사일런스 테라퓨틱스 아게 | 신규한 형태의 간섭 rna 분자 |
US20050042646A1 (en) | 2002-08-05 | 2005-02-24 | Davidson Beverly L. | RNA interference suppresion of neurodegenerative diseases and methods of use thereof |
ES2378987T3 (es) * | 2002-08-06 | 2012-04-19 | Toray Industries, Inc. | Remedio o agente preventivo para una enfermedad renal y procedimiento para diagnosticar una enfermedad renal |
SG166672A1 (en) * | 2002-08-06 | 2010-12-29 | Intradigm Corp | Methods of down regulating target gene expression in vivo by introduction of interfering rna |
US8729036B2 (en) | 2002-08-07 | 2014-05-20 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
US20040029275A1 (en) * | 2002-08-10 | 2004-02-12 | David Brown | Methods and compositions for reducing target gene expression using cocktails of siRNAs or constructs expressing siRNAs |
EP1536827B1 (en) * | 2002-08-14 | 2009-01-07 | Silence Therapeutics Aktiengesellschaft | Use of protein kinase n beta |
JP4717633B2 (ja) * | 2002-08-21 | 2011-07-06 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | 癌関連タンパク質を標的とするRNAiプローブ |
US7923547B2 (en) * | 2002-09-05 | 2011-04-12 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
US20060287269A1 (en) * | 2002-09-09 | 2006-12-21 | The Regents Of The University Of California | Short interfering nucleic acid hybrids and methods thereof |
US20080260744A1 (en) | 2002-09-09 | 2008-10-23 | Omeros Corporation | G protein coupled receptors and uses thereof |
US20040138119A1 (en) * | 2002-09-18 | 2004-07-15 | Ingo Tamm | Use of hepatitis B X-interacting protein (HBXIP) in modulation of apoptosis |
US20060257380A1 (en) * | 2002-09-19 | 2006-11-16 | Inst.Nat. De La Sante Et De La Recherche MED | Use of sirnas for gene silencing in antigen presenting cells |
EP1556402B1 (en) * | 2002-09-25 | 2011-06-22 | University of Massachusetts | In vivo gene silencing by chemically modified and stable sirna |
US20060160759A1 (en) * | 2002-09-28 | 2006-07-20 | Jianzhu Chen | Influenza therapeutic |
US20040242518A1 (en) * | 2002-09-28 | 2004-12-02 | Massachusetts Institute Of Technology | Influenza therapeutic |
AU2003279010A1 (en) * | 2002-09-28 | 2004-04-19 | Massachusetts Institute Of Technology | Compositions and methods for delivery of short interfering rna and short hairpin rna |
US20060240425A1 (en) * | 2002-09-30 | 2006-10-26 | Oncotherapy Science, Inc | Genes and polypeptides relating to myeloid leukemia |
US7422853B1 (en) * | 2002-10-04 | 2008-09-09 | Myriad Genetics, Inc. | RNA interference using a universal target |
AU2003291678B2 (en) | 2002-11-01 | 2009-01-15 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of HIF-1 alpha |
US7892793B2 (en) * | 2002-11-04 | 2011-02-22 | University Of Massachusetts | Allele-specific RNA interference |
EP1578765A4 (en) | 2002-11-05 | 2008-04-23 | Isis Pharmaceuticals Inc | OLIGOMERIC COMPOUNDS CONTAINING SUGAR SUBSTITUTE AND COMPOSITIONS FOR USE IN GENE MODULATION |
CA2504694C (en) | 2002-11-05 | 2013-10-01 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
US9150606B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2'-modified nucleosides for use in gene modulation |
CA2504554A1 (en) * | 2002-11-05 | 2004-05-27 | Isis Pharmaceuticals, Inc. | 2'-substituted oligomeric compounds and compositions for use in gene modulations |
US9150605B2 (en) | 2002-11-05 | 2015-10-06 | Isis Pharmaceuticals, Inc. | Compositions comprising alternating 2′-modified nucleosides for use in gene modulation |
DE10322662A1 (de) * | 2002-11-06 | 2004-10-07 | Grünenthal GmbH | Wirksame und stabile DNA-Enzyme |
US7655785B1 (en) | 2002-11-14 | 2010-02-02 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
US20090227780A1 (en) * | 2002-11-14 | 2009-09-10 | Dharmacon, Inc. | siRNA targeting connexin 43 |
US10011836B2 (en) | 2002-11-14 | 2018-07-03 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US9771586B2 (en) | 2002-11-14 | 2017-09-26 | Thermo Fisher Scientific Inc. | RNAi targeting ZNF205 |
US20080268457A1 (en) * | 2002-11-14 | 2008-10-30 | Dharmacon, Inc. | siRNA targeting forkhead box P3 (FOXP3) |
US9879266B2 (en) | 2002-11-14 | 2018-01-30 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US7781575B2 (en) | 2002-11-14 | 2010-08-24 | Dharmacon, Inc. | siRNA targeting tumor protein 53 (p53) |
US20090005548A1 (en) * | 2002-11-14 | 2009-01-01 | Dharmacon, Inc. | siRNA targeting nuclear receptor interacting protein 1 (NRIP1) |
US9719094B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting SEC61G |
US10920226B2 (en) * | 2002-11-14 | 2021-02-16 | Thermo Fisher Scientific Inc. | siRNA targeting LDHA |
WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
US7951935B2 (en) | 2002-11-14 | 2011-05-31 | Dharmacon, Inc. | siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC) |
US7612196B2 (en) * | 2002-11-14 | 2009-11-03 | Dharmacon, Inc. | siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B) |
US7619081B2 (en) | 2002-11-14 | 2009-11-17 | Dharmacon, Inc. | siRNA targeting coatomer protein complex, subunit beta 2 (COPB2) |
US8163896B1 (en) | 2002-11-14 | 2012-04-24 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
US8090542B2 (en) | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
US7250496B2 (en) | 2002-11-14 | 2007-07-31 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory genes and uses thereof |
US7592442B2 (en) * | 2002-11-14 | 2009-09-22 | Dharmacon, Inc. | siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2) |
US7977471B2 (en) * | 2002-11-14 | 2011-07-12 | Dharmacon, Inc. | siRNA targeting TNFα |
US7635770B2 (en) | 2002-11-14 | 2009-12-22 | Dharmacon, Inc. | siRNA targeting protein kinase N-3 (PKN-3) |
US7691998B2 (en) * | 2002-11-14 | 2010-04-06 | Dharmacon, Inc. | siRNA targeting nucleoporin 62kDa (Nup62) |
US9719092B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting CNTD2 |
US9839649B2 (en) | 2002-11-14 | 2017-12-12 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US20100113307A1 (en) * | 2002-11-14 | 2010-05-06 | Dharmacon, Inc. | siRNA targeting vascular endothelial growth factor (VEGF) |
US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
US8198427B1 (en) | 2002-11-14 | 2012-06-12 | Dharmacon, Inc. | SiRNA targeting catenin, beta-1 (CTNNB1) |
CA2506619A1 (en) | 2002-11-18 | 2004-08-19 | Thomas W. Hodge | Cell lines and host nucleic acid sequences related to infectious disease |
US7064337B2 (en) | 2002-11-19 | 2006-06-20 | The Regents Of The University Of California | Radiation detection system for portable gamma-ray spectroscopy |
DE10254214A1 (de) * | 2002-11-20 | 2004-06-09 | Beiersdorf Ag | Oligoribonukleotide zur Behandlung von degenerativen Hauterscheinungen durch RNA-Interferenz |
AU2003298718A1 (en) * | 2002-11-22 | 2004-06-18 | University Of Massachusetts | Modulation of hiv replication by rna interference |
EP2298886A3 (en) * | 2002-11-22 | 2011-12-14 | Bio-Think Tank Co., Ltd. | Method for searching target base sequence of RNA interference, method for designing base sequence of polynucleotide for causing RNA interference, method for producing double-stranded polynucleotide, method for inhibiting gene expression, base sequence processing apparatus, program for running base sequence processing method on computer, recording medium, and base sequence processing system |
JP4526228B2 (ja) * | 2002-11-22 | 2010-08-18 | 隆 森田 | RNAiによる新規治療法および治療剤 |
US7605249B2 (en) | 2002-11-26 | 2009-10-20 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
US7790867B2 (en) | 2002-12-05 | 2010-09-07 | Rosetta Genomics Inc. | Vaccinia virus-related nucleic acids and microRNA |
US7618948B2 (en) * | 2002-11-26 | 2009-11-17 | Medtronic, Inc. | Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA |
US20130130231A1 (en) | 2002-11-26 | 2013-05-23 | Isaac Bentwich | Bioinformatically detectable group of novel viral regulatory genes and uses thereof |
US7829694B2 (en) | 2002-11-26 | 2010-11-09 | Medtronic, Inc. | Treatment of neurodegenerative disease through intracranial delivery of siRNA |
ES2343318T3 (es) * | 2002-11-26 | 2010-07-28 | University Of Massachusetts | Administracion de arnsis. |
US7696334B1 (en) | 2002-12-05 | 2010-04-13 | Rosetta Genomics, Ltd. | Bioinformatically detectable human herpesvirus 5 regulatory gene |
CN1301263C (zh) * | 2002-12-18 | 2007-02-21 | 北京昭衍新药研究中心 | 一组抗hiv感染及防治艾滋病的核苷酸序列及其应用 |
US9498530B2 (en) | 2002-12-24 | 2016-11-22 | Rinat Neuroscience Corp. | Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same |
EP1575517B1 (en) | 2002-12-24 | 2012-04-11 | Rinat Neuroscience Corp. | Anti-ngf antibodies and methods using same |
EP2462936A1 (en) * | 2003-01-03 | 2012-06-13 | Gencia Corporation | SiRNA mediated post-transriptional gene-silencing of genes involved in alopecia |
CA2513623A1 (en) * | 2003-01-16 | 2004-08-05 | The Trustees Of The University Of Pennsylvania | Compositions and methods for sirna inhibition of icam-1 |
US7629323B2 (en) * | 2003-01-21 | 2009-12-08 | Northwestern University | Manipulation of neuronal ion channels |
US20060178297A1 (en) * | 2003-01-28 | 2006-08-10 | Troy Carol M | Systems and methods for silencing expression of a gene in a cell and uses thereof |
US20040147027A1 (en) * | 2003-01-28 | 2004-07-29 | Troy Carol M. | Complex for facilitating delivery of dsRNA into a cell and uses thereof |
US7994149B2 (en) | 2003-02-03 | 2011-08-09 | Medtronic, Inc. | Method for treatment of Huntington's disease through intracranial delivery of sirna |
US7732591B2 (en) | 2003-11-25 | 2010-06-08 | Medtronic, Inc. | Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna |
AU2004211949A1 (en) * | 2003-02-05 | 2004-08-26 | University Of Massachusetts | RNAi targeting of viruses |
FR2850971B1 (fr) * | 2003-02-10 | 2006-08-11 | Aventis Pharma Sa | Oligonucleotide antisens inhibant l'expression de la proteine ob-rgrp et procede de detection de composes modifiant l'interaction entre la famille de la proteine ob-rgrp et le recepteur de la leptine |
US20070104688A1 (en) | 2003-02-13 | 2007-05-10 | City Of Hope | Small interfering RNA mediated transcriptional gene silencing in mammalian cells |
US20040162235A1 (en) * | 2003-02-18 | 2004-08-19 | Trubetskoy Vladimir S. | Delivery of siRNA to cells using polyampholytes |
MXPA05008815A (es) | 2003-02-19 | 2006-05-25 | Rinat Neuroscience Corp | Metodos para tratar el dolor al administrar un antagonista del factor de crecimiento de nervios y un farmaco antiinflamatorio no esteroidal y composiciones que contienen los mismos. |
WO2005017127A2 (en) * | 2003-02-21 | 2005-02-24 | The Penn State Research Foundation | Rna interference compositions and methods |
WO2004076664A2 (en) * | 2003-02-21 | 2004-09-10 | University Of South Florida | Vectors for regulating gene expression |
US20060263764A1 (en) * | 2003-02-27 | 2006-11-23 | Nucleonics Inc. | Methods and constructs for evaluation of rnai targets and effector molecules |
KR20050103305A (ko) * | 2003-02-27 | 2005-10-28 | 내셔날 인스티튜트 오브 어드밴스드 인더스트리얼 사이언스 앤드 테크놀로지 | 포유 동물 세포에 있어서의 dsRNA에 의한 CpG서열로의 메틸화 유도 |
WO2004078940A2 (en) * | 2003-03-05 | 2004-09-16 | Senesco Technologies, Inc. | USE OF ANTISENSE OLIGONUCLEOTIDES OR siRNA TO SUPPRESS EXPRESSION OF eIF-5A1 |
US20050164212A1 (en) * | 2003-03-06 | 2005-07-28 | Todd Hauser | Modulation of gene expression using DNA-RNA hybrids |
US8110674B2 (en) | 2003-03-07 | 2012-02-07 | Alnylam Pharmaceuticals, Inc. | Therapeutic compositions |
EP1606305A4 (en) * | 2003-03-12 | 2009-06-24 | Vasgene Therapeutics Inc | NUCLEIC ACID COMPOUNDS FOR THE INHIBITION OF ANGIOGENESIS AND TUMOR GROWTH |
ES2576677T3 (es) † | 2003-03-21 | 2016-07-08 | Roche Innovation Center Copenhagen A/S | Análogos de ARN interfirientes cortos |
US20040198640A1 (en) * | 2003-04-02 | 2004-10-07 | Dharmacon, Inc. | Stabilized polynucleotides for use in RNA interference |
WO2004090105A2 (en) * | 2003-04-02 | 2004-10-21 | Dharmacon, Inc. | Modified polynucleotides for use in rna interference |
ATE536408T1 (de) * | 2003-04-02 | 2011-12-15 | Dharmacon Inc | Modifizierte polynukleotide zur verwendung bei rna-interferenz |
CA2521464C (en) | 2003-04-09 | 2013-02-05 | Alnylam Pharmaceuticals, Inc. | Irna conjugates |
WO2004091572A2 (en) | 2003-04-09 | 2004-10-28 | Biodelivery Sciences International, Inc. | Cochleate compositions directed against expression of proteins |
WO2004094345A2 (en) | 2003-04-17 | 2004-11-04 | Alnylam Pharmaceuticals Inc. | Protected monomers |
US20070270360A1 (en) * | 2003-04-15 | 2007-11-22 | Sirna Therapeutics, Inc. | Rna Interference Mediated Inhibition of Severe Acute Respiratory Syndrome (Sars) Gene Expression Using Short Interfering Nucleic Acid |
US8796436B2 (en) | 2003-04-17 | 2014-08-05 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
US8017762B2 (en) | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
EP2669377A3 (en) | 2003-04-17 | 2015-10-14 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
US7994305B2 (en) | 2003-04-18 | 2011-08-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods for siRNA inhibition of angiopoietin 1 and 2 and their receptor Tie2 |
US20070010468A1 (en) * | 2003-04-23 | 2007-01-11 | Georgetown University | Methods and compositions for the inhibition of stat5 in prostate cancer cells |
EP1644048B1 (en) * | 2003-05-05 | 2015-04-29 | Johns Hopkins University | Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein |
US7619068B2 (en) | 2003-05-09 | 2009-11-17 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
CA2523785A1 (en) | 2003-05-09 | 2004-11-25 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Small interfering rna libraries and methods of synthesis and use |
CN1780920B (zh) * | 2003-05-12 | 2012-03-28 | 波多玛克制药有限公司 | 基因表达抑制剂 |
WO2004104199A2 (en) * | 2003-05-15 | 2004-12-02 | Oligo Engine, Inc. | Modulation of gene expression using dna-dna hybrids |
WO2005018534A2 (en) * | 2003-05-16 | 2005-03-03 | Rosetta Inpharmatics, Llc | Methods and compositions for rna interference |
WO2004100990A1 (ja) | 2003-05-19 | 2004-11-25 | Genecare Research Institute Co., Ltd. | 癌細胞に対するアポトーシス誘導剤 |
WO2004106511A1 (ja) * | 2003-05-30 | 2004-12-09 | Nippon Shinyaku Co., Ltd. | Bcl−2の発現抑制をするオリゴ二本鎖RNAとそれを含有する医薬組成物 |
EP1637144A4 (en) * | 2003-05-30 | 2010-01-13 | Nippon Shinyaku Co Ltd | OLIGONUCLEIC ACID CONTAINING COMPOSITE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME |
US7750144B2 (en) | 2003-06-02 | 2010-07-06 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of RNA silencing |
DE602004029678D1 (de) * | 2003-06-02 | 2010-12-02 | Univ Massachusetts | Verfahren und zusammensetzungen zur verbesserung der wirksamkeit und spezifität von fnai |
AU2004248136B2 (en) * | 2003-06-02 | 2011-09-15 | University Of Massachusetts | Methods and compositions for controlling efficacy of RNA silencing |
BRPI0410886A (pt) * | 2003-06-03 | 2006-07-04 | Isis Pharmaceuticals Inc | composto de filamento duplo, composição farmacêutica, sal farmaceuticamente aceitável, métodos de modificação do ácido nucleico que codifica a survivina humana, de inibição da expressão da suvivina em células ou tecidos, e de tratamento de uma condição associada com a expressão ou superexpressão da suvivina, e, oligonucleotìdeo de rnai de filamento único |
US20050019918A1 (en) * | 2003-06-03 | 2005-01-27 | Hidetoshi Sumimoto | Treatment of cancer by inhibiting BRAF expression |
US7595306B2 (en) * | 2003-06-09 | 2009-09-29 | Alnylam Pharmaceuticals Inc | Method of treating neurodegenerative disease |
US8575327B2 (en) | 2003-06-12 | 2013-11-05 | Alnylam Pharmaceuticals, Inc. | Conserved HBV and HCV sequences useful for gene silencing |
US7786290B2 (en) | 2003-06-13 | 2010-08-31 | Alnylam Pharmaceuticals, Inc. | Double-stranded ribonucleic acid with increased effectiveness in an organism |
EP1486564A1 (de) * | 2003-06-13 | 2004-12-15 | Ribopharma AG | SiRNA mit erhöhter Stabilität in Serum |
US7790691B2 (en) * | 2003-06-20 | 2010-09-07 | Isis Pharmaceuticals, Inc. | Double stranded compositions comprising a 3′-endo modified strand for use in gene modulation |
EP1636342A4 (en) * | 2003-06-20 | 2008-10-08 | Isis Pharmaceuticals Inc | OLIGOMERIC COMPOUNDS FOR GENE MODULATION |
EP2371835A1 (en) * | 2003-07-03 | 2011-10-05 | The Trustees Of The University Of Pennsylvania | Inhibition of syk kinase expression |
JP2006528492A (ja) * | 2003-07-15 | 2006-12-21 | カリフォルニア インスティテュート オブ テクノロジー | 改良されたインヒビター核酸 |
US20050256071A1 (en) * | 2003-07-15 | 2005-11-17 | California Institute Of Technology | Inhibitor nucleic acids |
EP2567693B1 (en) * | 2003-07-16 | 2015-10-21 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering RNA |
WO2005010188A2 (en) * | 2003-07-21 | 2005-02-03 | Whitehead Institute For Biomedical Research | Rnas able to modulate chromatin silencing |
EP1648914A4 (en) | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
US7888497B2 (en) | 2003-08-13 | 2011-02-15 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
NZ545544A (en) * | 2003-08-13 | 2009-04-30 | Univ Illinois | Silencing of TGF-beta receptor type II expression by sirna |
US7825235B2 (en) * | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
WO2005035759A2 (en) * | 2003-08-20 | 2005-04-21 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF HYPOXIA INDUCIBLE FACTOR 1 (HIF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
US20050136437A1 (en) * | 2003-08-25 | 2005-06-23 | Nastech Pharmaceutical Company Inc. | Nanoparticles for delivery of nucleic acids and stable double-stranded RNA |
US20070203084A1 (en) | 2003-08-28 | 2007-08-30 | Jan Weiler | Interfering Rna Duplex Having Blunt-Ends And 3'-Modifications |
US8501705B2 (en) * | 2003-09-11 | 2013-08-06 | The Board Of Regents Of The University Of Texas System | Methods and materials for treating autoimmune and/or complement mediated diseases and conditions |
ES2485848T3 (es) * | 2003-09-12 | 2014-08-14 | University Of Massachusetts | ARN de interferencia para el tratamiento de trastornos relacionados con la ganancia de función |
US8680063B2 (en) | 2003-09-12 | 2014-03-25 | University Of Massachusetts | RNA interference for the treatment of gain-of-function disorders |
AU2004274942B2 (en) | 2003-09-18 | 2008-02-28 | Isis Pharmaceuticals, Inc. | Modulation of eIF4E expression |
EP1670955A2 (en) * | 2003-09-22 | 2006-06-21 | Rosetta Inpharmatics LLC. | Synthetic lethal screen using rna interference |
WO2005033310A1 (de) * | 2003-10-01 | 2005-04-14 | Grünenthal GmbH | Pim-1-spezifische dsrna-verbindungen |
US20080249038A1 (en) * | 2003-10-07 | 2008-10-09 | Quark Biotech, Inc. | Bone Morphogenetic Protein (Bmp) 2A and Uses Thereof |
WO2005052170A2 (en) | 2003-10-09 | 2005-06-09 | E. I. Du Pont De Nemours And Company | Gene silencing by using micro-rna molecules |
WO2005045032A2 (en) * | 2003-10-20 | 2005-05-19 | Sima Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF EARLY GROWTH RESPONSE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
WO2005045038A2 (en) * | 2003-10-23 | 2005-05-19 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GPRA AND AAA1 GENE EXPRESSION USING SHORT NUCLEIC ACID (siNA) |
EP1675953A2 (en) * | 2003-10-23 | 2006-07-05 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF RAS GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
CN1926551B (zh) | 2003-10-27 | 2010-06-16 | 罗斯塔生化科技有限责任公司 | 用于基因沉默的siRNA的设计方法 |
US8227434B1 (en) | 2003-11-04 | 2012-07-24 | H. Lee Moffitt Cancer Center & Research Institute, Inc. | Materials and methods for treating oncological disorders |
WO2005047504A1 (en) * | 2003-11-07 | 2005-05-26 | The Board Of Trustees Of The University Of Illinois | Induction of cellular senescence by cdk4 disruption for tumor suppression and regression |
EP1697515A4 (en) * | 2003-11-12 | 2008-02-06 | Austin Research Inst | CONJUGATE DNA-EXCIPIENT |
US7763592B1 (en) | 2003-11-20 | 2010-07-27 | University Of South Florida | SHIP-deficiency to increase megakaryocyte progenitor production |
JP2005168485A (ja) * | 2003-11-20 | 2005-06-30 | Tsutomu Suzuki | siRNAの設計方法 |
US7807646B1 (en) * | 2003-11-20 | 2010-10-05 | University Of South Florida | SHIP-deficiency to increase megakaryocyte progenitor production |
US20050208658A1 (en) * | 2003-11-21 | 2005-09-22 | The University Of Maryland | RNA interference mediated inhibition of 11beta hydroxysteriod dehydrogenase-1 (11beta HSD-1) gene expression |
US20100145038A1 (en) * | 2003-11-24 | 2010-06-10 | Merck & Co., Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
EP1694841A2 (en) * | 2003-11-26 | 2006-08-30 | The Queens University of Belfast | Cancer treatment |
EP1793674B1 (en) | 2003-11-26 | 2018-05-30 | University of Massachusetts | Sequence-specific inhibtion of small rna function |
US20070238676A1 (en) * | 2003-12-04 | 2007-10-11 | Mohapatra Shyam S | Polynucleotides for Reducing Respiratory Syncytial Virus Gene Expression |
WO2005059135A2 (en) * | 2003-12-12 | 2005-06-30 | Wisconsin Alumni Research Foundation | Treatment of mammals by sirna delivery into mammalian nerve cells |
JPWO2005068630A1 (ja) * | 2003-12-16 | 2007-07-26 | 独立行政法人産業技術総合研究所 | 干渉用二重鎖rna |
US20060134787A1 (en) | 2004-12-22 | 2006-06-22 | University Of Massachusetts | Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA |
CA2551100A1 (en) * | 2003-12-23 | 2005-07-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for combined therapy of disease |
EP1726313A4 (en) * | 2004-01-16 | 2008-04-09 | Takeda Pharmaceutical | MEDICAMENT FOR THE PREVENTION AND TREATMENT OF ARTERIOSCLEROSIS |
JP4755113B2 (ja) * | 2004-01-30 | 2011-08-24 | クアーク・ファーマスーティカルス、インコーポレイテッド | 線維性状態およびその他の疾患の治療のための、オリゴリボヌクレオチドおよびその使用方法 |
WO2005073378A1 (en) * | 2004-01-30 | 2005-08-11 | Santaris Pharma A/S | MODIFIED SHORT INTERFERING RNA (MODIFIED siRNA) |
ATE447024T1 (de) * | 2004-02-06 | 2009-11-15 | Dharmacon Inc | Stabilisierte rnas als transfektionskontrollen und silencing-reagentien |
ATE452188T1 (de) * | 2004-02-10 | 2010-01-15 | Sirna Therapeutics Inc | Rna-interferenz-vermittelte hemmung der genexpression unter verwendung multifunktioneller sina (short interfering nucleic acid) |
WO2005078848A2 (en) | 2004-02-11 | 2005-08-25 | University Of Tennessee Research Foundation | Inhibition of tumor growth and invasion by anti-matrix metalloproteinase dnazymes |
US20050273868A1 (en) * | 2004-02-17 | 2005-12-08 | University Of Massachusetts | Methods and compositions for enhancing RISC activity in vitro and in vivo |
WO2005079533A2 (en) * | 2004-02-17 | 2005-09-01 | University Of Massachusetts | Methods and compositions for mediating gene silencing |
EP1566202A1 (en) * | 2004-02-23 | 2005-08-24 | Sahltech I Göteborg AB | Use of resistin antagonists in the treatment of rheumatoid arthritis |
US20070202134A1 (en) * | 2004-02-23 | 2007-08-30 | Kufe Donald W | Muc1 Antagonist Enhancement of Death Receptor Ligand-Induced Apoptosis |
EP1723177A2 (en) | 2004-02-24 | 2006-11-22 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Rab9a, rab11a, and modulators thereof related to infectious disease |
US7691823B2 (en) * | 2004-03-05 | 2010-04-06 | University Of Massachusetts | RIP140 regulation of glucose transport |
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 |
US20050202075A1 (en) * | 2004-03-12 | 2005-09-15 | Pardridge William M. | Delivery of genes encoding short hairpin RNA using receptor-specific nanocontainers |
EP1735009A4 (en) | 2004-03-12 | 2011-03-30 | Alnylam Pharmaceuticals Inc | RNAI AGENTS TARGETING THE VASCULAR ENDOTHELIUM GROWTH FACTOR (VEGF) |
US20070265220A1 (en) | 2004-03-15 | 2007-11-15 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
US20050277610A1 (en) * | 2004-03-15 | 2005-12-15 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
US20050208090A1 (en) * | 2004-03-18 | 2005-09-22 | Medtronic, Inc. | Methods and systems for treatment of neurological diseases of the central nervous system |
US20050272682A1 (en) * | 2004-03-22 | 2005-12-08 | Evers Bernard M | SiRNA targeting PI3K signal transduction pathway and siRNA-based therapy |
US7851452B2 (en) * | 2004-03-22 | 2010-12-14 | The Trustees Of The University Of Pennsylvania | Methods of use of bcl-6-derived nucleotides to induce apoptosis |
EP1730280B1 (en) * | 2004-03-26 | 2018-10-24 | Curis, Inc. | Rna interference modulators of hedgehog signaling and uses thereof |
US7872117B2 (en) * | 2004-03-26 | 2011-01-18 | Van Andel Research Institute | c-met siRNA adenovirus vectors inhibit cancer cell growth, invasion and tumorigenicity |
JP2005312428A (ja) * | 2004-03-31 | 2005-11-10 | Keio Gijuku | Skp−2発現抑制を利用した癌の治療 |
JPWO2005095647A1 (ja) * | 2004-03-31 | 2008-02-21 | タカラバイオ株式会社 | siRNAのスクリーニング方法 |
KR101147147B1 (ko) | 2004-04-01 | 2012-05-25 | 머크 샤프 앤드 돔 코포레이션 | Rna 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드 |
AU2005230684B2 (en) * | 2004-04-05 | 2011-10-06 | Alnylam Pharmaceuticals, Inc. | Process and reagents for oligonucleotide synthesis and purification |
US8193332B2 (en) | 2004-04-09 | 2012-06-05 | Genecare Research Institute Co., Ltd. | Cancer cell-specific apoptosis-inducing agents that target chromosome stabilization-associated genes |
US20060078902A1 (en) * | 2004-04-15 | 2006-04-13 | Michaeline Bunting | Method and compositions for RNA interference |
EP1773998A2 (en) * | 2004-04-20 | 2007-04-18 | Nastech Pharmaceutical Company Inc. | Methods and compositions for enhancing delivery of double-stranded rna or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells |
WO2005105157A2 (en) | 2004-04-23 | 2005-11-10 | The Trustees Of Columbia University In The City Ofnew York | INHIBITION OF HAIRLESS PROTEIN mRNA |
JP4584986B2 (ja) * | 2004-04-27 | 2010-11-24 | アルニラム ファーマスーティカルズ インコーポレイテッド | 2−アリールプロピル部分を含む1本鎖及び2本鎖オリゴヌクレオチド |
US8029815B2 (en) | 2004-04-28 | 2011-10-04 | Elford Howard L | Methods for treating or preventing restenosis and other vascular proliferative disorders |
JP4584987B2 (ja) | 2004-04-30 | 2010-11-24 | アルニラム ファーマスーティカルズ インコーポレイテッド | C5修飾ピリミジンを含むオリゴヌクレオチド |
US20060040882A1 (en) * | 2004-05-04 | 2006-02-23 | Lishan Chen | Compostions and methods for enhancing delivery of nucleic acids into cells and for modifying expression of target genes in cells |
US7605250B2 (en) | 2004-05-12 | 2009-10-20 | Dharmacon, Inc. | siRNA targeting cAMP-specific phosphodiesterase 4D |
US20050260214A1 (en) * | 2004-05-12 | 2005-11-24 | Simon Michael R | Composition and method for introduction of RNA interference sequences into targeted cells and tissues |
US20060030003A1 (en) * | 2004-05-12 | 2006-02-09 | Simon Michael R | Composition and method for introduction of RNA interference sequences into targeted cells and tissues |
US20110117088A1 (en) * | 2004-05-12 | 2011-05-19 | Simon Michael R | Composition and method for introduction of rna interference sequences into targeted cells and tissues |
EP1784501B1 (en) | 2004-05-14 | 2015-11-18 | Rosetta Genomics Ltd | VIRAL AND VIRUS ASSOCIATED MicroRNAS AND USES THEREOF |
WO2005110464A2 (en) * | 2004-05-14 | 2005-11-24 | Oregon Health & Science University | Irx5 inhibition as treatment for hyperproliferative disorders |
US7687616B1 (en) | 2004-05-14 | 2010-03-30 | Rosetta Genomics Ltd | Small molecules modulating activity of micro RNA oligonucleotides and micro RNA targets and uses thereof |
US10508277B2 (en) | 2004-05-24 | 2019-12-17 | Sirna Therapeutics, Inc. | Chemically modified multifunctional short interfering nucleic acid molecules that mediate RNA interference |
US7964196B2 (en) * | 2004-05-25 | 2011-06-21 | Chimeros, Inc. | Self-assembling nanoparticle drug delivery system |
US7795419B2 (en) | 2004-05-26 | 2010-09-14 | Rosetta Genomics Ltd. | Viral and viral associated miRNAs and uses thereof |
EP2290070B1 (en) | 2004-05-28 | 2015-03-25 | Asuragen, Inc. | Methods and compositions involving microRNA |
US8394947B2 (en) | 2004-06-03 | 2013-03-12 | Isis Pharmaceuticals, Inc. | Positionally modified siRNA constructs |
EP1602926A1 (en) | 2004-06-04 | 2005-12-07 | University of Geneva | Novel means and methods for the treatment of hearing loss and phantom hearing |
EP1766035B1 (en) | 2004-06-07 | 2011-12-07 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering rna |
JP4764426B2 (ja) * | 2004-06-07 | 2011-09-07 | プロチバ バイオセラピューティクス インコーポレイティッド | カチオン性脂質および使用方法 |
US20060008907A1 (en) * | 2004-06-09 | 2006-01-12 | The Curators Of The University Of Missouri | Control of gene expression via light activated RNA interference |
US20090215860A1 (en) * | 2004-06-17 | 2009-08-27 | The Regents Of The University Of California | Compositions and methods for regulating gene transcription |
US20060051815A1 (en) * | 2004-06-25 | 2006-03-09 | The J. David Gladstone Institutes | Methods of treating smooth muscle cell disorders |
WO2006088490A2 (en) | 2004-06-30 | 2006-08-24 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a non-phosphate backbone linkage |
US7807815B2 (en) * | 2004-07-02 | 2010-10-05 | Protiva Biotherapeutics, Inc. | Compositions comprising immunostimulatory siRNA molecules and DLinDMA or DLenDMA |
EP1765378B1 (en) | 2004-07-12 | 2014-04-16 | Medical Research Fund of Tel Aviv Sourasky Medical Center | Agent capable of downregulating an msf-a-dependent hif-1a and use thereof in cancer treatment |
JP2008522951A (ja) * | 2004-07-19 | 2008-07-03 | ベイラー・カレツジ・オブ・メデイシン | サイトカインシグナル伝達調節物質の調節および免疫療法のための応用 |
JP2008507341A (ja) * | 2004-07-21 | 2008-03-13 | メドトロニック,インコーポレイティド | 限局性繊維症を低減するための医療装置及び方法 |
CA2574088C (en) | 2004-07-21 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
US20060030538A1 (en) * | 2004-07-21 | 2006-02-09 | Medtronic, Inc. | Methods for reducing or preventing localized fibrosis using SiRNA |
EP2484780A1 (en) | 2004-07-23 | 2012-08-08 | The University of North Carolina At Chapel Hill | Methods and materials for determining pain sensibility and predicting and treating related disorders |
US7632932B2 (en) | 2004-08-04 | 2009-12-15 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
US7741299B2 (en) | 2004-08-16 | 2010-06-22 | Quark Pharmaceuticals, Inc. | Therapeutic uses of inhibitors of RTP801 |
WO2006020557A2 (en) * | 2004-08-10 | 2006-02-23 | Immusol, Inc. | Methods of using or identifying agents that inhibit cancer growth |
WO2006020768A2 (en) | 2004-08-10 | 2006-02-23 | Alnylam Pharmaceuticals, Inc. | Chemically modified oligonucleotides |
WO2006110161A2 (en) * | 2004-08-13 | 2006-10-19 | University Of Delaware | Method for identification and quantification of short or small rna molecules |
US20070021366A1 (en) * | 2004-11-19 | 2007-01-25 | Srivastava Satish K | Structural-based inhibitors of the glutathione binding site in aldose reductase, methods of screening therefor and methods of use |
SI1781787T1 (sl) * | 2004-08-23 | 2017-08-31 | Sylentis S.A.U. | Zdravljenje očesnih nepravilnosti, kakakterističnih za povišan očesni tlak s sirna |
US7323310B2 (en) | 2004-08-31 | 2008-01-29 | Qiagen North American Holdings, Inc. | Methods and compositions for RNA amplification and detection using an RNA-dependent RNA-polymerase |
AU2005278918B2 (en) * | 2004-08-31 | 2010-07-29 | Sylentis S.A.U. | Methods and compositions to inhibit P2X7 receptor expression |
US7884086B2 (en) * | 2004-09-08 | 2011-02-08 | Isis Pharmaceuticals, Inc. | Conjugates for use in hepatocyte free uptake assays |
US20090170794A1 (en) * | 2004-09-10 | 2009-07-02 | Somagenics Inc. | Small interfering rnas that efficiently inhibit viral expression and methods of use thereof |
WO2006033965A2 (en) * | 2004-09-16 | 2006-03-30 | The Trustees Of The University Of Pennsylvania | Nadph oxidase inhibition pharmacotherapies for obstructive sleep apnea syndrome and its associated morbidities |
FI20041204A0 (fi) | 2004-09-16 | 2004-09-16 | Riikka Lund | Menetelmät immuunivälitteisiin sairauksiin liittyvien uusien kohdegeenien hyödyntämiseksi |
AU2005289588B2 (en) * | 2004-09-24 | 2011-12-22 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of ApoB and uses thereof |
KR101409241B1 (ko) | 2004-09-28 | 2014-06-24 | 쿠아크 파마수티칼스 인코퍼레이티드 | 탈모증, 급성신부전증 및 다른 질환의 치료를 위한 올리고리보뉴클레오티드 및 그것의 사용방법 |
WO2006039343A2 (en) * | 2004-09-30 | 2006-04-13 | Centocor, Inc. | Emmprin antagonists and uses thereof |
EP2336333A1 (en) | 2004-10-21 | 2011-06-22 | Venganza Inc. | Methods and materials for conferring resistance to pests and pathogens of plants |
CN101084309A (zh) * | 2004-10-22 | 2007-12-05 | 诺伊热尼有限公司 | 神经元再生 |
US20060089324A1 (en) * | 2004-10-22 | 2006-04-27 | Sailen Barik | RNAi modulation of RSV, PIV and other respiratory viruses and uses thereof |
US20060110440A1 (en) * | 2004-10-22 | 2006-05-25 | Kiminobu Sugaya | Method and system for biasing cellular development |
US7790878B2 (en) * | 2004-10-22 | 2010-09-07 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of RSV, PIV and other respiratory viruses and uses thereof |
JP2008517629A (ja) * | 2004-10-27 | 2008-05-29 | シェーリング コーポレイション | Nav1.8の短い干渉核酸阻害のための組成物および方法 |
EP2311530A2 (en) | 2004-10-27 | 2011-04-20 | Vanderbilt University | Mammalian genes involved in infection |
WO2006050002A2 (en) * | 2004-10-28 | 2006-05-11 | Idexx Laboratories, Inc. | Compositions for controlled delivery of pharmaceutically active compounds |
US20060094676A1 (en) * | 2004-10-29 | 2006-05-04 | Ronit Lahav | Compositions and methods for treating cancer using compositions comprising an inhibitor of endothelin receptor activity |
US9492400B2 (en) | 2004-11-04 | 2016-11-15 | Massachusetts Institute Of Technology | Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals |
WO2008073922A2 (en) * | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Functions and targets of let-7 micro rnas |
EP2322616A1 (en) | 2004-11-12 | 2011-05-18 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
US8809287B2 (en) * | 2004-11-15 | 2014-08-19 | Icahn School Of Medicine At Mount Sinai | Compositions and methods for altering Wnt autocrine signaling |
US20060105052A1 (en) * | 2004-11-15 | 2006-05-18 | Acar Havva Y | Cationic nanoparticle having an inorganic core |
EP2199298A1 (en) * | 2004-11-17 | 2010-06-23 | Protiva Biotherapeutics Inc. | Sirna silencing of Apolipoprotein B |
AU2005307737C1 (en) * | 2004-11-18 | 2013-08-29 | The Board Of Trustees Of The University Of Illinois | Multicistronic siRNA constructs to inhibit tumors |
US8314073B2 (en) * | 2004-11-19 | 2012-11-20 | Genecare Research Institute Co., Ltd. | Cancer-cell-specific cell proliferation inhibitors |
US7923207B2 (en) | 2004-11-22 | 2011-04-12 | Dharmacon, Inc. | Apparatus and system having dry gene silencing pools |
US20060166234A1 (en) * | 2004-11-22 | 2006-07-27 | Barbara Robertson | Apparatus and system having dry control gene silencing compositions |
US7935811B2 (en) | 2004-11-22 | 2011-05-03 | Dharmacon, Inc. | Apparatus and system having dry gene silencing compositions |
CA2587697A1 (en) * | 2004-11-24 | 2006-07-13 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of the bcr-abl fusion gene and uses thereof |
US20060160110A1 (en) * | 2004-12-02 | 2006-07-20 | Takayuki Mizutani | Methods of designing small interfering RNAs, antisense polynucleotides, and other hybridizing polynucleotides |
WO2006060779A2 (en) * | 2004-12-03 | 2006-06-08 | Case Western Reserve University | Novel methods, compositions and devices for inducing neovascularization |
ATE544774T1 (de) * | 2004-12-14 | 2012-02-15 | Alnylam Pharmaceuticals Inc | Rnai-modulation von mll-af4 und verwendungen dafür |
EP2270136A1 (en) | 2004-12-17 | 2011-01-05 | Beth Israel Deaconess Medical Center | Compositions for bacterial mediated gene silencing and methods of using same |
GB0427916D0 (en) * | 2004-12-21 | 2005-01-19 | Astrazeneca Ab | Method |
TWI386225B (zh) | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子(CTGF)RNA干擾(RNAi)抑制技術 |
US20060142228A1 (en) * | 2004-12-23 | 2006-06-29 | Ambion, Inc. | Methods and compositions concerning siRNA's as mediators of RNA interference |
US8852472B2 (en) | 2004-12-27 | 2014-10-07 | Silence Therapeutics Gmbh | Coated lipid complexes and their use |
JP2008526213A (ja) * | 2004-12-30 | 2008-07-24 | トッド エム. ハウザー, | 自己保護オリゴヌクレオチドを使用する、遺伝子発現を調節するための組成物および方法 |
WO2006073970A2 (en) * | 2005-01-06 | 2006-07-13 | The Johns Hopkins University | Rna interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by dna and transfected dendritic cell vaccines |
ES2343746T3 (es) | 2005-01-07 | 2010-08-09 | Diadexus, Inc. | Composiciones de anticuerpo ovr110 y metodos de uso. |
ATE551421T1 (de) * | 2005-01-07 | 2012-04-15 | Alnylam Pharmaceuticals Inc | Rnai modulation von rsv und deren therapeutische verwendungen |
EP1841464B1 (en) * | 2005-01-24 | 2012-06-27 | Alnylam Pharmaceuticals Inc. | Rnai modulation of the nogo-l or nogo-r gene and uses thereof |
JP2008528004A (ja) * | 2005-01-26 | 2008-07-31 | ザ ジョンズ ホプキンス ユニバーシティー | 突然変異癌タンパク質抗原およびカルレティキュリンをコードするプラスミドを用いる抗癌dnaワクチン |
TW200639252A (en) * | 2005-02-01 | 2006-11-16 | Alcon Inc | RNAi-mediated inhibition of ocular hypertension targets |
EP2302076B1 (en) | 2005-02-14 | 2014-11-12 | University of Iowa Research Foundation | Methods and reagents for treatment and diagnosis of age-related macular degeneration |
EP1848805A2 (en) * | 2005-02-14 | 2007-10-31 | HVC Strategic Research Institute, Inc | Pharmaceutical agents for preventing metastasis of cancer |
EP2157182A3 (en) * | 2005-03-08 | 2012-04-25 | Qiagen GmbH | Modified short interfering RNA |
BRPI0609206A2 (pt) | 2005-03-11 | 2010-03-02 | Alcon Inc | inibiÇço mediada por rnai de proteÍna relacionada frizzled-1 para tratamento de glaucoma |
GB0505081D0 (en) * | 2005-03-14 | 2005-04-20 | Genomica Sau | Downregulation of interleukin-12 expression by means of rnai technology |
US8999943B2 (en) * | 2005-03-14 | 2015-04-07 | Board Of Regents, The University Of Texas System | Antigene oligomers inhibit transcription |
JP4585342B2 (ja) * | 2005-03-18 | 2010-11-24 | 株式会社資生堂 | 不全角化を抑制する物質のスクリーニング方法、同方法によりスクリーニングされた物質及び不全角化を抑制する方法 |
ATE524546T1 (de) * | 2005-03-25 | 2011-09-15 | Medtronic Inc | Verwendung von anti-tnf oder anti-il1-rnai zur unterdrückung der wirkung entzündungsfördernder cytokine zur lokalen schmerzbehandlung |
EP2360249A1 (en) * | 2005-03-31 | 2011-08-24 | Calando Pharmaceuticals, Inc. | Inhibitors of ribonucleotide reductase subunit 2 and uses thereof |
US20090203055A1 (en) * | 2005-04-18 | 2009-08-13 | Massachusetts Institute Of Technology | Compositions and methods for RNA interference with sialidase expression and uses thereof |
US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
US20060257912A1 (en) | 2005-05-06 | 2006-11-16 | Medtronic, Inc. | Methods and sequences to suppress primate huntington gene expression |
EP2298829B1 (en) * | 2005-05-31 | 2017-09-20 | École Polytechnique Fédérale de Lausanne (EPFL) | Triblock copolymers for cytoplasmic delivery of gene-based drugs |
US20070048293A1 (en) * | 2005-05-31 | 2007-03-01 | The Trustees Of The University Of Pennsylvania | Manipulation of PTEN in T cells as a strategy to modulate immune responses |
US20100286228A1 (en) * | 2005-06-01 | 2010-11-11 | Duke University | Method of inhibiting intimal hyperplasia |
DK1888749T3 (en) * | 2005-06-01 | 2015-01-05 | Polyplus Transfection | Oligonucleotides for RNA interference and their biological applications |
US20100266574A1 (en) * | 2005-06-10 | 2010-10-21 | Orna Mor | Oligoribonucleotides and Methods of Use Thereof for Treatment of Fibrotic Conditions and Other Diseases |
CN100445381C (zh) * | 2005-06-10 | 2008-12-24 | 中国人民解放军军事医学科学院基础医学研究所 | 带有单链polyA尾巴的siRNA分子制备方法和应用 |
WO2006138145A1 (en) | 2005-06-14 | 2006-12-28 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
US7838503B2 (en) * | 2005-06-15 | 2010-11-23 | Children's Medical Center Corporation | Methods for extending the replicative lifespan of cells |
FI20050640A0 (fi) * | 2005-06-16 | 2005-06-16 | Faron Pharmaceuticals Oy | Yhdisteitä amiinioksidaasista riippuvien sairauksien tai häiriöiden hoitoon tai estoon |
US7868159B2 (en) * | 2005-06-23 | 2011-01-11 | Baylor College Of Medicine | Modulation of negative immune regulators and applications for immunotherapy |
EP1896084A4 (en) * | 2005-06-27 | 2010-10-20 | Alnylam Pharmaceuticals Inc | RNAI MODULATION OF HIF-1 AND THERAPEUTIC APPLICATIONS THEREOF |
US9133517B2 (en) | 2005-06-28 | 2015-09-15 | Medtronics, Inc. | Methods and sequences to preferentially suppress expression of mutated huntingtin |
EP1915448B1 (en) * | 2005-07-07 | 2013-09-04 | Yissum Research Development Company, of The Hebrew University of Jerusalem | Nucleic acid agents for downregulating h19, and methods of using same |
WO2007011702A2 (en) | 2005-07-15 | 2007-01-25 | The University Of North Carolina At Chapel Hill | Use of egfr inhibitors to prevent or treat obesity |
JP5383189B2 (ja) * | 2005-07-25 | 2014-01-08 | リボックス・ゲーエムベーハー | Rna依存性rnaポリメラーゼ、rnaを増幅するため及び/又は標識するための方法並びにキット |
WO2007014370A2 (en) * | 2005-07-28 | 2007-02-01 | University Of Delaware | Small regulatory rnas and methods of use |
US7919583B2 (en) | 2005-08-08 | 2011-04-05 | Discovery Genomics, Inc. | Integration-site directed vector systems |
US20070213257A1 (en) * | 2005-08-12 | 2007-09-13 | Nastech Pharmaceutical Company Inc. | Compositions and methods for complexes of nucleic acids and peptides |
US20070105803A1 (en) | 2005-08-18 | 2007-05-10 | Muthiah Manoharan | Methods and compositions for treating neurological disease |
US20070054873A1 (en) * | 2005-08-26 | 2007-03-08 | Protiva Biotherapeutics, Inc. | Glucocorticoid modulation of nucleic acid-mediated immune stimulation |
US8501703B2 (en) | 2005-08-30 | 2013-08-06 | Isis Pharmaceuticals, Inc. | Chimeric oligomeric compounds for modulation of splicing |
US20090018097A1 (en) * | 2005-09-02 | 2009-01-15 | Mdrna, Inc | Modification of double-stranded ribonucleic acid molecules |
US20090221673A1 (en) * | 2005-09-13 | 2009-09-03 | Rigby William F C | Compositions and Methods for Regulating RNA Translation via CD154 CA-Dinucleotide Repeat |
AU2006298844B2 (en) | 2005-09-20 | 2012-01-12 | Basf Plant Science Gmbh | Methods for controlling gene expression using ta-siRAN |
FR2890859B1 (fr) * | 2005-09-21 | 2012-12-21 | Oreal | Oligonucleotide d'arn double brin inhibant l'expression de la tyrosinase |
US8933043B2 (en) * | 2005-09-30 | 2015-01-13 | St. Jude Children's Research Hospital | Methods for regulation of p53 translation and function |
US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
US8080534B2 (en) | 2005-10-14 | 2011-12-20 | Phigenix, Inc | Targeting PAX2 for the treatment of breast cancer |
US7838658B2 (en) * | 2005-10-20 | 2010-11-23 | Ian Maclachlan | siRNA silencing of filovirus gene expression |
GB0521351D0 (en) * | 2005-10-20 | 2005-11-30 | Genomica Sau | Modulation of TRPV expression levels |
GB0521716D0 (en) * | 2005-10-25 | 2005-11-30 | Genomica Sau | Modulation of 11beta-hydroxysteriod dehydrogenase 1 expression for the treatment of ocular diseases |
US8076307B2 (en) * | 2005-10-27 | 2011-12-13 | National University Corporation NARA Institute of Science and Technology | Formation/elongation of axon by inhibiting the expression or function of Singar and application to nerve regeneration |
EP1941059A4 (en) * | 2005-10-28 | 2010-11-03 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR INHIBITING THE EXPRESSION OF THE HUNTINGTIN GENE |
EP1948674A4 (en) | 2005-11-02 | 2009-02-04 | Protiva Biotherapeutics Inc | MODIFIED SIRNA MOLECULES AND APPLICATIONS THEREOF |
CA2626584A1 (en) * | 2005-11-04 | 2007-05-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of nav1.8 gene |
EP1951318B1 (en) * | 2005-11-07 | 2012-10-17 | British Columbia Cancer Agency | Inhibition of autophagy genes in cancer chemotherapy |
US20100069461A1 (en) | 2005-11-09 | 2010-03-18 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of factor v leiden mutant 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 |
US8916530B2 (en) | 2005-11-18 | 2014-12-23 | Gradalis, Inc. | Individualized cancer therapy |
US8603991B2 (en) | 2005-11-18 | 2013-12-10 | Gradalis, Inc. | Individualized cancer therapy |
US20080125384A1 (en) * | 2005-11-21 | 2008-05-29 | Shuewi Yang | Simultaneous silencing and restoration of gene function |
WO2007061022A1 (ja) * | 2005-11-24 | 2007-05-31 | Jichi Medical University | プロヒビチン2(phb2)のミトコンドリア機能 |
US9267937B2 (en) | 2005-12-15 | 2016-02-23 | Massachusetts Institute Of Technology | System for screening particles |
DE602006014026D1 (de) * | 2005-12-22 | 2010-06-10 | Opko Ophthalmics Llc | Zusammensetzungen und verfahren zur regulierung eines komplementsystems |
AR057252A1 (es) * | 2005-12-27 | 2007-11-21 | Alcon Mfg Ltd | Inhibicion de rho quinasa mediada por arni para el tratamiento de trastornos oculares |
JP5713377B2 (ja) | 2005-12-28 | 2015-05-07 | ザ スクリプス リサーチ インスティテュート | 薬物標的としての天然アンチセンスおよび非コードrna転写物 |
US8673873B1 (en) * | 2005-12-28 | 2014-03-18 | Alcon Research, Ltd. | RNAi-mediated inhibition of phosphodiesterase type 4 for treatment of cAMP-related ocular disorders |
EP1973574B1 (en) * | 2005-12-30 | 2014-04-02 | Institut Gustave Roussy | Use of inhibitors of scinderin and/or of ephrin-a1 for treating tumors |
US20090060921A1 (en) * | 2006-01-17 | 2009-03-05 | Biolex Therapeutics, Inc. | Glycan-optimized anti-cd20 antibodies |
MX2008009221A (es) * | 2006-01-17 | 2008-11-27 | Biolex Therapeutics Inc | Composiciones y metodos para la humanizacion y optimizacion de n-glicanos en plantas. |
EP2671954B1 (en) | 2006-01-20 | 2018-05-16 | Cell Signaling Technology, Inc. | Translocation and mutant ROS kinase in human non-small cell lung carcinoma |
US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
UY30097A1 (es) | 2006-01-20 | 2007-08-31 | Atugen Ag | Usos terapeuticos de inhibidores de rtp801 |
US7825099B2 (en) | 2006-01-20 | 2010-11-02 | Quark Pharmaceuticals, Inc. | Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes |
US20070259827A1 (en) * | 2006-01-25 | 2007-11-08 | University Of Massachusetts | Compositions and methods for enhancing discriminatory RNA interference |
AU2007209481B2 (en) * | 2006-01-27 | 2012-01-12 | Roche Innovation Center Copenhagen A/S | LNA modified phosphorothiolated oligonucleotides |
US8229398B2 (en) * | 2006-01-30 | 2012-07-24 | Qualcomm Incorporated | GSM authentication in a CDMA network |
WO2007091269A2 (en) * | 2006-02-08 | 2007-08-16 | Quark Pharmaceuticals, Inc. | NOVEL TANDEM siRNAS |
US7910566B2 (en) | 2006-03-09 | 2011-03-22 | Quark Pharmaceuticals Inc. | Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA |
FI20060246A0 (fi) | 2006-03-16 | 2006-03-16 | Jukka Westermarck | Uusi kasvua stimuloiva proteiini ja sen käyttö |
US20100056441A1 (en) * | 2006-03-17 | 2010-03-04 | Costa Robert H | Method for Inhibiting Angiogenesis |
EA015563B1 (ru) | 2006-03-23 | 2011-08-30 | Сантарис Фарма А/С | Короткая внутренне сегментированная интерферирующая рнк |
WO2007111998A2 (en) * | 2006-03-24 | 2007-10-04 | Novartis Ag | Dsrna compositions and methods for treating hpv infection |
FR2898908A1 (fr) | 2006-03-24 | 2007-09-28 | Agronomique Inst Nat Rech | Procede de preparation de cellules aviaires differenciees et genes impliques dans le maintien de la pluripotence |
WO2007115047A2 (en) * | 2006-03-29 | 2007-10-11 | Senesco Technologies, Inc. | Inhibition of hiv replication and expression of p24 with eif-5a |
WO2008105773A2 (en) | 2006-03-31 | 2008-09-04 | Massachusetts Institute Of Technology | System for targeted delivery of therapeutic agents |
NZ587704A (en) | 2006-03-31 | 2012-04-27 | Alnylam Pharmaceuticals Inc | Use of dsRNA for inhibiting expression of Eg5 gene |
US20090226446A1 (en) * | 2006-04-06 | 2009-09-10 | Deutsches Krebsforschungszentrum Stiftung Des Offentilchen Rechts | Method to Inhibit the Propagation of an Undesired Cell Population |
US9044461B2 (en) | 2006-04-07 | 2015-06-02 | The Research Foundation Of State University Of New York | Transcobalamin receptor polypeptides, nucleic acids, and modulators thereof, and related methods of use in modulating cell growth and treating cancer and cobalamin deficiency |
WO2008108776A1 (en) * | 2006-04-07 | 2008-09-12 | Chimeros, Inc. | Compositions and methods for treating b- cell malignancies |
WO2007117657A2 (en) | 2006-04-07 | 2007-10-18 | The Research Foundation Of State University Of New York | Transcobalamin receptor polypeptides, nucleic acids, and modulators thereof, and related methods of use in modulating cell growth and treating cancer and cobalamin deficiency |
WO2007120883A2 (en) * | 2006-04-12 | 2007-10-25 | Isis Pharmaceuticals, Inc. | Compositions and their uses directed to hepcidin |
US20100055116A1 (en) * | 2006-04-13 | 2010-03-04 | Liou Hsiou-Chi | Methods and Compositions for Targeting c-Rel |
EP2447360A1 (en) | 2006-04-14 | 2012-05-02 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
JP2009533458A (ja) * | 2006-04-14 | 2009-09-17 | マサチューセッツ インスティテュート オブ テクノロジー | 神経系の可塑性を媒介する分子経路の同定および変調 |
WO2007127919A2 (en) * | 2006-04-28 | 2007-11-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a gene from the jc virus |
GB0608838D0 (en) | 2006-05-04 | 2006-06-14 | Novartis Ag | Organic compounds |
PL2194128T3 (pl) * | 2006-05-11 | 2012-12-31 | Alnylam Pharmaceuticals Inc | Kompozycje i sposoby inhibicji ekspresji genu PCSK9 |
EP2019691B1 (en) | 2006-05-15 | 2020-08-12 | Massachusetts Institute of Technology | Polymers for functional particles |
WO2007133758A1 (en) * | 2006-05-15 | 2007-11-22 | Physical Pharmaceutica, Llc | Composition and improved method for preparation of small particles |
US20070269892A1 (en) * | 2006-05-18 | 2007-11-22 | Nastech Pharmaceutical Company Inc. | FORMULATIONS FOR INTRACELLULAR DELIVERY dsRNA |
US7812150B2 (en) * | 2006-05-19 | 2010-10-12 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of Aha and therapeutic uses thereof |
WO2007137239A2 (en) * | 2006-05-19 | 2007-11-29 | The Scripps Research Institute | Treatment of protein misfolding |
CA2653451C (en) * | 2006-05-22 | 2015-12-29 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of ikk-b gene |
US9273356B2 (en) | 2006-05-24 | 2016-03-01 | Medtronic, Inc. | Methods and kits for linking polymorphic sequences to expanded repeat mutations |
US20070275923A1 (en) * | 2006-05-25 | 2007-11-29 | Nastech Pharmaceutical Company Inc. | CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY |
GB0610542D0 (en) * | 2006-05-26 | 2006-07-05 | Medical Res Council | Screening method |
US8598333B2 (en) * | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
EP2026843A4 (en) | 2006-06-09 | 2011-06-22 | Quark Pharmaceuticals Inc | THERAPEUTIC USES OF RTP801L INHIBITORS |
US7915399B2 (en) | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
EP2029746B1 (en) * | 2006-06-12 | 2012-07-04 | Exegenics, Inc., D/b/a Opko Health, Inc. | Compositions and methods for sirna inhibition of angiogenesis |
US9200275B2 (en) * | 2006-06-14 | 2015-12-01 | Merck Sharp & Dohme Corp. | Methods and compositions for regulating cell cycle progression |
WO2007150030A2 (en) | 2006-06-23 | 2007-12-27 | Massachusetts Institute Of Technology | Microfluidic synthesis of organic nanoparticles |
US8124752B2 (en) * | 2006-07-10 | 2012-02-28 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the MYC gene |
GB0613753D0 (en) * | 2006-07-11 | 2006-08-23 | Norwegian Radium Hospital Res | Method |
DK2447275T3 (en) | 2006-07-13 | 2015-06-29 | Univ Iowa Res Found | Methods and reagents for the treatment of age-related macular degeneration |
JP4756271B2 (ja) * | 2006-07-18 | 2011-08-24 | 独立行政法人産業技術総合研究所 | ガン細胞の老化、アポトーシス誘導剤 |
RU2553561C2 (ru) | 2006-07-21 | 2015-06-20 | Сайленс Терапьютикс Аг | Средства ингибирования экспрессии протеинкиназы 3 |
US20080039415A1 (en) * | 2006-08-11 | 2008-02-14 | Gregory Robert Stewart | Retrograde transport of sirna and therapeutic uses to treat neurologic disorders |
WO2008024844A2 (en) * | 2006-08-22 | 2008-02-28 | The Johns Hopkins University | Anticancer combination therapies |
DE102006039479A1 (de) | 2006-08-23 | 2008-03-06 | Febit Biotech Gmbh | Programmierbare Oligonukleotidsynthese |
US7872118B2 (en) * | 2006-09-08 | 2011-01-18 | Opko Ophthalmics, Llc | siRNA and methods of manufacture |
JP2010504350A (ja) * | 2006-09-19 | 2010-02-12 | アシュラジェン インコーポレイテッド | 治療的介入の標的としての、miR−200によって調節される遺伝子および経路 |
CA2663962A1 (en) * | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
US20090209478A1 (en) | 2006-09-21 | 2009-08-20 | Tomoko Nakayama | Compositions and methods for inhibiting expression of the hamp gene |
EP2081949B1 (en) | 2006-09-22 | 2014-12-10 | GE Healthcare Dharmacon, Inc. | Tripartite oligonucleotide complexes and methods for gene silencing by rna interference |
JP2010505897A (ja) * | 2006-10-11 | 2010-02-25 | マックス−プランク−ゲゼルシャフト・ツア・フェルデルング・デア・ヴィッセンシャフテン・エー・ファオ | インフルエンザターゲット |
WO2008063760A2 (en) * | 2006-10-18 | 2008-05-29 | The University Of Texas M.D. Anderson Cancer Center | Methods for treating cancer targeting transglutaminase |
JP2010507387A (ja) * | 2006-10-25 | 2010-03-11 | クアーク・ファーマスーティカルス、インコーポレイテッド | 新規のsiRNAおよびその使用方法 |
WO2008052774A2 (en) | 2006-10-31 | 2008-05-08 | Noxxon Pharma Ag | Methods for detection of a single- or double-stranded nucleic acid molecule |
EP2078079B1 (en) | 2006-11-01 | 2011-05-04 | The Medical Research and Infrastructure Fund of the Tel-Aviv Sourasky Medical Center | Adipocyte-specific constructs and methods for inhibiting platelet-type 12 lipoxygenase expression |
US9375440B2 (en) | 2006-11-03 | 2016-06-28 | Medtronic, Inc. | Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity |
US8324367B2 (en) | 2006-11-03 | 2012-12-04 | Medtronic, Inc. | Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity |
US8906874B2 (en) | 2006-11-09 | 2014-12-09 | Gradalis, Inc. | Bi-functional shRNA targeting Stathmin 1 and uses thereof |
US8758998B2 (en) | 2006-11-09 | 2014-06-24 | Gradalis, Inc. | Construction of bifunctional short hairpin RNA |
US8252526B2 (en) * | 2006-11-09 | 2012-08-28 | Gradalis, Inc. | ShRNA molecules and methods of use thereof |
US7988668B2 (en) | 2006-11-21 | 2011-08-02 | Medtronic, Inc. | Microsyringe for pre-packaged delivery of pharmaceuticals |
US7819842B2 (en) | 2006-11-21 | 2010-10-26 | Medtronic, Inc. | Chronically implantable guide tube for repeated intermittent delivery of materials or fluids to targeted tissue sites |
US8034921B2 (en) * | 2006-11-21 | 2011-10-11 | Alnylam Pharmaceuticals, Inc. | IRNA agents targeting CCR5 expressing cells and uses thereof |
JP5271715B2 (ja) * | 2006-11-22 | 2013-08-21 | 国立大学法人 東京大学 | ジスルフィド架橋高分子ミセルを用いた環境応答性siRNAキャリア |
AU2007325283B2 (en) | 2006-11-27 | 2012-08-30 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
JP2010510772A (ja) | 2006-11-27 | 2010-04-08 | パトリス リミテッド | 新生細胞における新規なグリコシル化ペプチド標的 |
WO2008067373A2 (en) * | 2006-11-28 | 2008-06-05 | Alcon Research, Ltd. | RNAi-MEDIATED INHIBITION OF AQUAPORIN 1 FOR TREATMENT OF IOP-RELATED CONDITIONS |
US20080261907A1 (en) * | 2006-11-30 | 2008-10-23 | University Of Southern California | Compositions and methods of sphingosine kinase inhibitors in radiation therapy of various cancers |
CA2671294A1 (en) * | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Mir-21 regulated genes and pathways as targets for therapeutic intervention |
CA2672606A1 (en) * | 2006-12-14 | 2008-06-26 | Novartis Ag | Compositions and methods to treat muscular & cardiovascular disorders |
CA2671270A1 (en) * | 2006-12-29 | 2008-07-17 | Asuragen, Inc. | Mir-16 regulated genes and pathways as targets for therapeutic intervention |
US7754698B2 (en) * | 2007-01-09 | 2010-07-13 | Isis Pharmaceuticals, Inc. | Modulation of FR-alpha expression |
US9896511B2 (en) | 2007-01-10 | 2018-02-20 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies that bind to TL1A and methods of treating inflammatory or autoimmune disease comprising administering such antibodies |
AU2007344641B2 (en) | 2007-01-16 | 2014-05-22 | The University Of Queensland | Method of inducing an immune response |
US7928083B2 (en) * | 2007-01-16 | 2011-04-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | H19 silencing nucleic acid agents for treating rheumatoid arthritis |
US20080171906A1 (en) * | 2007-01-16 | 2008-07-17 | Everaerts Frank J L | Tissue performance via hydrolysis and cross-linking |
WO2008088836A2 (en) * | 2007-01-16 | 2008-07-24 | The Burnham Institute For Medical Research | Compositions and methods for treatment of colorectal cancer |
CA2712073A1 (en) * | 2007-01-17 | 2008-07-24 | Institut De Recherches Cliniques De Montreal | Nucleoside and nucleotide analogues with quaternary carbon centers and methods of use |
US8455188B2 (en) | 2007-01-26 | 2013-06-04 | University Of Louisville Research Foundation, Inc. | Modification of exosomal components for use as a vaccine |
WO2008093331A1 (en) * | 2007-01-29 | 2008-08-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Antibody conjugates for circumventing multi-drug resistance |
US20100183696A1 (en) * | 2007-01-30 | 2010-07-22 | Allergan, Inc | Treating Ocular Diseases Using Peroxisome Proliferator-Activated Receptor Delta Antagonists |
WO2008098165A2 (en) | 2007-02-09 | 2008-08-14 | Massachusetts Institute Of Technology | Oscillating cell culture bioreactor |
MX2009008470A (es) | 2007-02-09 | 2009-11-26 | Univ Northwestern | Particulas para detectar objetivos intracelulares. |
DE102007008596B4 (de) * | 2007-02-15 | 2010-09-02 | Friedrich-Schiller-Universität Jena | Biologisch wirksame Moleküle auf Grundlage von PNA und siRNA, Verfahren zu deren zellspezifischen Aktivierung sowie Applikationskit zur Verabreichung |
WO2008103643A1 (en) | 2007-02-20 | 2008-08-28 | Monsanto Technology, Llc | Invertebrate micrornas |
EP2137205A2 (en) | 2007-02-26 | 2009-12-30 | Quark Pharmaceuticals, Inc. | Inhibitors of rtp801 and their use in disease treatment |
US20100292301A1 (en) * | 2007-02-28 | 2010-11-18 | Elena Feinstein | Novel sirna structures |
US20080299659A1 (en) * | 2007-03-02 | 2008-12-04 | Nastech Pharmaceutical Company Inc. | Nucleic acid compounds for inhibiting apob gene expression and uses thereof |
WO2008109034A2 (en) * | 2007-03-02 | 2008-09-12 | The Trustees Of The University Of Pennsylvania | Modulating pdx-1 with pcif1, methods 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 |
US9085638B2 (en) | 2007-03-07 | 2015-07-21 | The Johns Hopkins University | DNA vaccine enhancement with MHC class II activators |
US20080260765A1 (en) * | 2007-03-15 | 2008-10-23 | Johns Hopkins University | HPV DNA Vaccines and Methods of Use Thereof |
HUE027018T2 (en) | 2007-03-21 | 2016-08-29 | Brookhaven Science Ass Llc | Combination hairpin antisense compositions and methods for modulating expression |
US7812002B2 (en) | 2007-03-21 | 2010-10-12 | Quark Pharmaceuticals, Inc. | Oligoribonucleotide inhibitors of NRF2 and methods of use thereof for treatment of cancer |
PE20090064A1 (es) * | 2007-03-26 | 2009-03-02 | Novartis Ag | Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende |
AU2008232891B2 (en) * | 2007-03-29 | 2012-01-12 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a gene from the Ebola |
WO2008124634A1 (en) | 2007-04-04 | 2008-10-16 | Massachusetts Institute Of Technology | Polymer-encapsulated reverse micelles |
WO2008124639A2 (en) * | 2007-04-04 | 2008-10-16 | Massachusetts Institute Of Technology | Poly (amino acid) targeting moieties |
US20090226525A1 (en) * | 2007-04-09 | 2009-09-10 | Chimeros Inc. | Self-assembling nanoparticle drug delivery system |
JP5258874B2 (ja) | 2007-04-10 | 2013-08-07 | キアゲン ゲゼルシャフト ミット ベシュレンクテル ハフツング | Rna干渉タグ |
AU2008242842B2 (en) * | 2007-04-17 | 2014-06-05 | Baxter Healthcare Sa | Nucleic acid microparticles for pulmonary delivery |
WO2008131419A2 (en) * | 2007-04-23 | 2008-10-30 | Alnylam Pharmaceuticals, Inc. | Glycoconjugates of rna interference agents |
WO2008143774A2 (en) * | 2007-05-01 | 2008-11-27 | University Of Massachusetts | Methods and compositions for locating snp heterozygosity for allele specific diagnosis and therapy |
EP2607477B1 (en) | 2007-05-03 | 2020-09-23 | The Brigham and Women's Hospital, Inc. | Multipotent stem cells and uses thereof |
JP5296328B2 (ja) * | 2007-05-09 | 2013-09-25 | 独立行政法人理化学研究所 | 1本鎖環状rnaおよびその製造方法 |
CN102014928A (zh) * | 2007-05-15 | 2011-04-13 | 海利空医疗公司 | 使用小干扰RNA(siRNA)鉴别参与记忆形成的基因的方法 |
AU2008254905A1 (en) * | 2007-05-15 | 2008-11-27 | Helicon Therapeutics, Inc. | Methods of treating cognitive disorders by inhibition of Gpr12 |
BRPI0811170B8 (pt) | 2007-05-22 | 2021-05-25 | Arcturus Therapeutics Inc | oligonucleotídeos de rna e complexos de rna substituídos por hidroximetila |
US20090131354A1 (en) * | 2007-05-22 | 2009-05-21 | Bader Andreas G | miR-126 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION |
CA2689923A1 (en) | 2007-05-30 | 2008-12-11 | Northwestern University | Nucleic acid functionalized nanoparticles for therapeutic applications |
JP5616220B2 (ja) | 2007-06-01 | 2014-10-29 | ザ トラスティーズ オブ プリンストン ユニバーシティ | 宿主細胞代謝経路の調節によるウイルス感染治療 |
JP5271901B2 (ja) * | 2007-06-11 | 2013-08-21 | タカラバイオ株式会社 | 特異的遺伝子発現方法 |
US20100273854A1 (en) * | 2007-06-15 | 2010-10-28 | Hagar Kalinski | Compositions and methods for inhibiting nadph oxidase expression |
AR066984A1 (es) | 2007-06-15 | 2009-09-23 | Novartis Ag | Inhibicion de la expresion de la subunidad alfa del canal epitelial de sodio (enac) por medio de arni (arn de interferencia) |
PL2170403T3 (pl) | 2007-06-27 | 2014-09-30 | Quark Pharmaceuticals Inc | Kompozycje i sposoby hamowania ekspresji genów proapoptotycznych |
JP5547964B2 (ja) * | 2007-06-29 | 2014-07-16 | 株式会社ステリック再生医科学研究所 | 生理活性物質を定着および発現させる方法 |
CN101688206B (zh) * | 2007-07-05 | 2013-05-15 | 诺瓦提斯公司 | 用于治疗病毒感染的dsRNA |
WO2009007934A2 (en) * | 2007-07-10 | 2009-01-15 | Neurim Pharmaceuticals (1991) Ltd. | Cd44 splice variants in neurodegenerative diseases |
US8828960B2 (en) * | 2007-07-17 | 2014-09-09 | Idexx Laboratories, Inc. | Amino acid vitamin ester compositions for controlled delivery of pharmaceutically active compounds |
JP2009033986A (ja) * | 2007-07-31 | 2009-02-19 | Sumitomo Chemical Co Ltd | RNA干渉による遺伝子発現抑制のためのターゲット遺伝子としてのcar遺伝子の使用 |
EP2030615A3 (en) | 2007-08-13 | 2009-12-02 | ELFORD, Howard L. | Ribonucleotide reductase inhibitors for use in the treatment or prevention of neuroinflammatory or autoimmune diseases |
US8501929B2 (en) * | 2007-08-17 | 2013-08-06 | Biochrom Pharma Inc. | PTHrP, its isoforms and antagonist thereto in the diagnosis and treatment of disease |
ES2873350T3 (es) * | 2007-08-27 | 2021-11-03 | 1Globe Health Inst Llc | Composiciones de ARN interferente asimétrico y usos de las mismas |
JP2010536392A (ja) * | 2007-08-30 | 2010-12-02 | ヴィレックス メディカル コーポレイション | 抗原性組成物および核酸の標的化送達におけるその使用 |
US20090081789A1 (en) * | 2007-08-31 | 2009-03-26 | Greenville Hospital System | Activation of nuclear factor kappa B |
US8183221B2 (en) | 2007-09-05 | 2012-05-22 | Medtronic, Inc. | Suppression of SCN9A gene expression and/or function for the treatment of pain |
JP5049713B2 (ja) * | 2007-09-14 | 2012-10-17 | 株式会社コナミデジタルエンタテインメント | ゲームシステム並びにこれを構成するゲーム装置及び課題報知装置 |
KR20100065190A (ko) * | 2007-09-14 | 2010-06-15 | 닛토덴코 가부시키가이샤 | 약물 담체 |
US8361714B2 (en) | 2007-09-14 | 2013-01-29 | Asuragen, Inc. | Micrornas differentially expressed in cervical cancer and uses thereof |
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 |
EP2197454A4 (en) * | 2007-09-25 | 2012-07-04 | Idexx Lab Inc | PHARMACEUTICAL COMPOSITIONS FOR THE ADMINISTRATION OF OLIGONUCLEOTIDES |
ES2647538T3 (es) | 2007-09-28 | 2017-12-22 | Pfizer Inc. | Direccionamiento a células de cáncer usando nanopartículas |
US20120082659A1 (en) * | 2007-10-02 | 2012-04-05 | Hartmut Land | Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations |
WO2009044392A2 (en) | 2007-10-03 | 2009-04-09 | Quark Pharmaceuticals, Inc. | Novel sirna structures |
EP2205746A4 (en) * | 2007-10-04 | 2010-12-22 | Univ Texas | MODULATION OF GENE EXPRESSION WITH AGRNA AND GAPS WITH ANTISENSE TRANSCRIPTS AS A TARGET |
EP2620157A3 (en) | 2007-10-12 | 2013-10-16 | Massachusetts Institute of Technology | Vaccine nanotechnology |
EP3741851A1 (en) | 2007-10-18 | 2020-11-25 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
US8097712B2 (en) | 2007-11-07 | 2012-01-17 | Beelogics Inc. | Compositions for conferring tolerance to viral disease in social insects, and the use thereof |
US20100098664A1 (en) * | 2007-11-28 | 2010-04-22 | Mathieu Jean-Francois Desclaux | Lentiviral vectors allowing RNAi mediated inhibition of GFAP and vimentin expression |
WO2009082593A2 (en) * | 2007-11-30 | 2009-07-02 | Baylor College Of Medicine | Dendritic cell vaccine compositions and uses of same |
WO2009070805A2 (en) | 2007-12-01 | 2009-06-04 | Asuragen, Inc. | Mir-124 regulated genes and pathways as targets for therapeutic intervention |
CA2706317C (en) | 2007-12-03 | 2017-06-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Doc1 compositions and methods for treating cancer |
WO2009082606A2 (en) * | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Folate conjugates |
WO2009082607A2 (en) | 2007-12-04 | 2009-07-02 | Alnylam Pharmaceuticals, Inc. | Targeting lipids |
EP2245159A2 (en) | 2007-12-10 | 2010-11-03 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of factor vii gene |
US20110105584A1 (en) * | 2007-12-12 | 2011-05-05 | Elena Feinstein | Rtp80il 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 |
EP2229459B1 (en) | 2007-12-13 | 2014-08-27 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for prevention or treatment of RSV infection |
US20090176729A1 (en) * | 2007-12-14 | 2009-07-09 | Alnylam Pharmaceuticals, Inc. | Method of treating neurodegenerative disease |
US7845686B2 (en) * | 2007-12-17 | 2010-12-07 | S & B Technical Products, Inc. | Restrained pipe joining system for plastic pipe |
KR100949791B1 (ko) * | 2007-12-18 | 2010-03-30 | 이동기 | 오프-타겟 효과를 최소화하고 RNAi 기구를 포화시키지않는 신규한 siRNA 구조 및 그 용도 |
US20090192114A1 (en) * | 2007-12-21 | 2009-07-30 | Dmitriy Ovcharenko | miR-10 Regulated Genes and Pathways as Targets for Therapeutic Intervention |
WO2009090639A2 (en) * | 2008-01-15 | 2009-07-23 | Quark Pharmaceuticals, Inc. | Sirna compounds and methods of use thereof |
CA2713379A1 (en) * | 2008-01-31 | 2009-11-05 | Alnylam Pharmaceuticals, Inc. | Optimized methods for delivery of dsrna targeting the pcsk9 gene |
US20090263803A1 (en) * | 2008-02-08 | 2009-10-22 | Sylvie Beaudenon | Mirnas differentially expressed in lymph nodes from cancer patients |
US8188060B2 (en) | 2008-02-11 | 2012-05-29 | Dharmacon, Inc. | Duplex oligonucleotides with enhanced functionality in gene regulation |
CN104975020B (zh) | 2008-02-11 | 2020-01-17 | 菲奥医药公司 | 经修饰的RNAi多核苷酸及其用途 |
US8288525B2 (en) * | 2008-02-12 | 2012-10-16 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of CD45 gene |
US7977321B2 (en) * | 2008-02-12 | 2011-07-12 | University Of Tennessee Research Foundation | Small interfering RNAs targeting feline herpes virus |
DE102009043743B4 (de) | 2009-03-13 | 2016-10-13 | Friedrich-Schiller-Universität Jena | Zellspezifisch wirksame Moleküle auf Grundlage von siRNA sowie Applikationskits zu deren Herstellung und Verwendung |
US20110207796A1 (en) * | 2008-02-13 | 2011-08-25 | Elan Pharma International Limited | Alpha-synuclein kinase |
WO2009103067A2 (en) * | 2008-02-14 | 2009-08-20 | The Children's Hospital Of Philadelphia | Compositions and methods to treat asthma |
EP2712926A2 (en) * | 2008-03-05 | 2014-04-02 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of Eg5 and VEGF genes |
US20090233297A1 (en) * | 2008-03-06 | 2009-09-17 | Elizabeth Mambo | Microrna markers for recurrence of colorectal cancer |
JP5653899B2 (ja) * | 2008-03-17 | 2015-01-14 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 神経筋シナプスの維持および再生に関与するマイクロrnaの同定 |
AU2009227549A1 (en) * | 2008-03-20 | 2009-09-24 | Quark Pharmaceuticals, Inc. | Novel siRNA compounds for inhibiting RTP801 |
WO2009154835A2 (en) * | 2008-03-26 | 2009-12-23 | Asuragen, Inc. | Compositions and methods related to mir-16 and therapy of prostate cancer |
EP2105145A1 (en) * | 2008-03-27 | 2009-09-30 | ETH Zürich | Method for muscle-specific delivery lipid-conjugated oligonucleotides |
BRPI0910446A8 (pt) * | 2008-03-31 | 2016-07-26 | Nat Inst Of Advanced Ind Scien | rna modificado por lipídeo de filamento duplo tendo alto efeito de interferência de rna |
TWI348916B (en) * | 2008-04-03 | 2011-09-21 | Univ Nat Taiwan | A novel treatment tool for cancer: rna interference of bcas2 |
WO2009126726A1 (en) * | 2008-04-08 | 2009-10-15 | Asuragen, Inc | Methods and compositions for diagnosing and modulating human papillomavirus (hpv) |
CA2721183C (en) | 2008-04-11 | 2019-07-16 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
WO2009126913A1 (en) | 2008-04-11 | 2009-10-15 | Cedars-Sinai Medical Center | Poly(beta malic acid) with pendant leu-leu-leu tripeptide for effective cytoplasmic drug delivery |
NZ588583A (en) | 2008-04-15 | 2012-08-31 | Protiva Biotherapeutics Inc | Novel lipid formulations for nucleic acid delivery |
EP2285385A4 (en) * | 2008-04-15 | 2013-01-16 | Quark Pharmaceuticals Inc | COMPOUNDS BASED ON RNSI TO INHIBIT NRF2 |
WO2009129465A2 (en) * | 2008-04-17 | 2009-10-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of xbp-1 gene |
US20090285861A1 (en) * | 2008-04-17 | 2009-11-19 | Tzyy-Choou Wu | Tumor cell-based cancer immunotherapeutic compositions and methods |
USRE48948E1 (en) | 2008-04-18 | 2022-03-01 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable polymer |
US9005599B2 (en) | 2008-04-21 | 2015-04-14 | Tissue Regeneration Therapeutics Inc. | Genetically modified human umbilical cord perivascular cells for prophylaxis against or treatment of biological or chemical agents |
US8324366B2 (en) | 2008-04-29 | 2012-12-04 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for delivering RNAI using lipoproteins |
WO2009134443A2 (en) * | 2008-05-02 | 2009-11-05 | The Brigham And Women's Hospital, Inc. | Rna-induced translational silencing and cellular apoptosis |
EP2990487A1 (en) | 2008-05-08 | 2016-03-02 | Asuragen, INC. | Compositions and methods related to mirna modulation of neovascularization or angiogenesis |
US20090291073A1 (en) * | 2008-05-20 | 2009-11-26 | Ward Keith W | Compositions Comprising PKC-theta and Methods for Treating or Controlling Ophthalmic Disorders Using Same |
WO2009146417A1 (en) * | 2008-05-30 | 2009-12-03 | Sigma-Aldrich Co. | Compositions and methods for specifically silencing a target nucleic acid |
AU2009256243A1 (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 |
US20090305611A1 (en) * | 2008-06-06 | 2009-12-10 | Flow International Corporation | Device and method for improving accuracy of a high-pressure fluid jet apparatus |
WO2009147684A2 (en) | 2008-06-06 | 2009-12-10 | Quark Pharmaceuticals, Inc. | Compositions and methods for treatment of ear disorders |
WO2009150156A1 (en) * | 2008-06-13 | 2009-12-17 | Riboxx Gmbh | Method for enzymatic synthesis of chemically modified rna |
WO2010005741A1 (en) * | 2008-06-16 | 2010-01-14 | Georgia Tech Research Corporation | Nanogels for cellular delivery of therapeutics |
TWI455944B (zh) | 2008-07-01 | 2014-10-11 | Daiichi Sankyo Co Ltd | 雙股多核苷酸 |
US20110184046A1 (en) | 2008-07-11 | 2011-07-28 | Dinah Wen-Yee Sah | Compositions And Methods For Inhibiting Expression Of GSK-3 Genes |
WO2010008562A2 (en) | 2008-07-16 | 2010-01-21 | Recombinetics | Methods and materials for producing transgenic animals |
US8815818B2 (en) | 2008-07-18 | 2014-08-26 | Rxi Pharmaceuticals Corporation | Phagocytic cell delivery of RNAI |
US8039658B2 (en) * | 2008-07-25 | 2011-10-18 | Air Products And Chemicals, Inc. | Removal of trace arsenic impurities from triethylphosphate (TEPO) |
WO2010014857A2 (en) * | 2008-07-30 | 2010-02-04 | University Of Massachusetts | Chromosome therapy |
EP2323695B1 (en) | 2008-08-19 | 2018-12-05 | Nektar Therapeutics | Complexes of small-interfering nucleic acids |
NZ601660A (en) | 2008-08-25 | 2014-05-30 | Excaliard Pharmaceuticals Inc | Antisense oligonucleotides directed against connective tissue growth factor and uses thereof |
WO2011028218A1 (en) | 2009-09-02 | 2011-03-10 | Alnylam Pharmaceuticals, Inc. | Process for triphosphate oligonucleotide synthesis |
BRPI0919017A2 (pt) * | 2008-09-15 | 2017-05-30 | Children's Medical Center Corp | métodos para aumentar níveis de hemoglobina fetal em uma célula e em mamífero em necessidade do mesmo, e, para identificar um modulador de expressão ou atividade de bcl11a |
CN108165548B (zh) | 2008-09-22 | 2022-10-14 | 菲奥医药公司 | 减小大小的自递送RNAi化合物 |
WO2010039548A2 (en) | 2008-09-23 | 2010-04-08 | Alnylam Pharmaceuticals, Inc. | Chemical modifications of monomers and oligonucleotides with cycloaddition |
EP3109321B1 (en) | 2008-09-25 | 2019-05-01 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene |
US8592570B2 (en) * | 2008-10-06 | 2013-11-26 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of an RNA from West Nile virus |
US9149492B2 (en) | 2008-10-08 | 2015-10-06 | Trustees Of Dartmouth College | Method for selectively inhibiting ACAT1 in the treatment of alzheimer's disease |
WO2010042292A1 (en) * | 2008-10-08 | 2010-04-15 | Trustees Of Dartmouth College | Method for selectively inhibiting the activity of acat1 in the treatment of alzheimer's disease |
US9388414B2 (en) | 2008-10-08 | 2016-07-12 | Trustees Of Dartmouth College | Method for selectively inhibiting ACAT1 in the treatment of neurodegenerative diseases |
US8802646B2 (en) * | 2008-10-08 | 2014-08-12 | Trustees Of Dartmouth College | Method for selectively inhibiting the activity of ACAT1 in the treatment of alzheimer's disease |
US9388413B2 (en) | 2008-10-08 | 2016-07-12 | Trustees Of Dartmouth College | Method for selectively inhibiting ACAT1 in the treatment of neurodegenerative diseases |
CA2740000C (en) | 2008-10-09 | 2017-12-12 | Tekmira Pharmaceuticals Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
US8591905B2 (en) | 2008-10-12 | 2013-11-26 | The Brigham And Women's Hospital, Inc. | Nicotine immunonanotherapeutics |
US8343498B2 (en) | 2008-10-12 | 2013-01-01 | Massachusetts Institute Of Technology | Adjuvant incorporation in immunonanotherapeutics |
US8277812B2 (en) | 2008-10-12 | 2012-10-02 | Massachusetts Institute Of Technology | Immunonanotherapeutics that provide IgG humoral response without T-cell antigen |
US8343497B2 (en) | 2008-10-12 | 2013-01-01 | The Brigham And Women's Hospital, Inc. | Targeting of antigen presenting cells with immunonanotherapeutics |
EP2352744B1 (en) | 2008-10-15 | 2016-09-21 | Somagenics, Inc. | Short hairpin rnas for inhibition of gene expression |
US9458472B2 (en) * | 2008-10-15 | 2016-10-04 | Massachusetts Institute Of Technology | Detection and destruction of cancer cells using programmed genetic vectors |
KR20160079921A (ko) | 2008-10-20 | 2016-07-06 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스티레틴의 발현을 억제하기 위한 조성물 및 방법 |
US20100168205A1 (en) * | 2008-10-23 | 2010-07-01 | Alnylam Pharmaceuticals, Inc. | Methods and Compositions for Prevention or Treatment of RSV Infection Using Modified Duplex RNA Molecules |
US20110190380A1 (en) * | 2008-10-23 | 2011-08-04 | Elena Feinstein | Methods for delivery of sirna to bone marrow cells and uses thereof |
CN105152939A (zh) | 2008-11-10 | 2015-12-16 | 阿尔尼拉姆医药品有限公司 | 用于递送治疗剂的脂质和组合物 |
US20100179213A1 (en) * | 2008-11-11 | 2010-07-15 | Mirna Therapeutics, Inc. | Methods and Compositions Involving miRNAs In Cancer Stem Cells |
JP2012508770A (ja) * | 2008-11-13 | 2012-04-12 | モッドジーン リミテッド ライアビリティ カンパニー | 非脳組織におけるアミロイドβ負荷の変更 |
US9074211B2 (en) | 2008-11-19 | 2015-07-07 | Rxi Pharmaceuticals Corporation | Inhibition of MAP4K4 through RNAI |
WO2010059575A2 (en) | 2008-11-21 | 2010-05-27 | Isis Pharmaceuticals, Inc. | Combination therapy for the treatment of cancer |
WO2010060110A1 (en) | 2008-11-24 | 2010-05-27 | Northwestern University | Polyvalent rna-nanoparticle compositions |
EP2191834A1 (en) * | 2008-11-26 | 2010-06-02 | Centre National De La Recherche Scientifique (Cnrs) | Compositions and methods for treating retrovirus infections |
SG10201500318SA (en) | 2008-12-03 | 2015-03-30 | Arcturus Therapeutics Inc | UNA Oligomer Structures For Therapeutic Agents |
US20100291188A1 (en) * | 2008-12-04 | 2010-11-18 | Musc Foundation For Research Development | Periostin Inhibitory Compositions for Myocardial Regeneration, Methods of Delivery, and Methods of Using Same |
US8470792B2 (en) | 2008-12-04 | 2013-06-25 | Opko Pharmaceuticals, Llc. | Compositions and methods for selective inhibition of VEGF |
KR20220047668A (ko) | 2008-12-09 | 2022-04-18 | 제넨테크, 인크. | 항-pd-l1 항체 및 t 세포 기능을 향상시키기 위한 그의 용도 |
EP2373382B1 (en) | 2008-12-10 | 2017-02-15 | Alnylam Pharmaceuticals, Inc. | Gnaq targeted dsrna compositions and methods for inhibiting expression |
EP2356236B1 (en) * | 2008-12-11 | 2015-07-29 | Xiangxue Group (Hong Kong) Company Limited | siRNA COMPOSITIONS AND METHODS FOR POTENTLY INHIBITING VIRAL INFECTION |
US8389711B2 (en) * | 2008-12-12 | 2013-03-05 | Kureha Corporation | Pharmaceutical composition for treatment of cancer and asthma |
WO2010077894A2 (en) | 2008-12-16 | 2010-07-08 | Bristol-Myers Squibb Company | Methods of inhibiting quiescent tumor proliferation |
WO2010080452A2 (en) | 2008-12-18 | 2010-07-15 | Quark Pharmaceuticals, Inc. | siRNA COMPOUNDS AND METHODS OF USE THEREOF |
KR101209265B1 (ko) | 2008-12-26 | 2012-12-06 | 주식회사 삼양바이오팜 | 음이온성 약물 함유 약제학적 조성물 및 그 제조방법 |
WO2010078536A1 (en) | 2009-01-05 | 2010-07-08 | Rxi Pharmaceuticals Corporation | Inhibition of pcsk9 through rnai |
US20100233270A1 (en) | 2009-01-08 | 2010-09-16 | Northwestern University | Delivery of Oligonucleotide-Functionalized Nanoparticles |
WO2010083532A1 (en) * | 2009-01-19 | 2010-07-22 | The Research Foundaton Of State University Of New York | Fatty acid binding proteins as drug targets for modulation of endocannabinoids |
CA2750044A1 (en) * | 2009-01-20 | 2010-07-29 | Vib Vzw | Phd2 inhibition for blood vessel normalization, and uses thereof |
EP2405921A4 (en) | 2009-01-26 | 2013-05-22 | Protiva Biotherapeutics Inc | COMPOSITIONS AND METHODS FOR INACTIVATION OF APOLIPOPROTEIN C-III EXPRESSION |
KR20110100316A (ko) * | 2009-02-03 | 2011-09-09 | 에프. 호프만-라 로슈 아게 | Ptp1b 유전자의 발현을 억제하기 위한 조성물 및 방법 |
WO2010090762A1 (en) | 2009-02-04 | 2010-08-12 | Rxi Pharmaceuticals Corporation | Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
PL2881402T3 (pl) | 2009-02-12 | 2017-10-31 | Cell Signaling Technology Inc | Ekspresja zmutowanej ROS w ludzkim raku wątroby |
DE10704945T8 (de) | 2009-02-24 | 2013-04-25 | Riboxx Gmbh | Verbesserte konstruktion von small-interfering-rna |
EP2403863B1 (en) | 2009-03-02 | 2013-08-28 | Alnylam Pharmaceuticals Inc. | Nucleic acid chemical modifications |
EA201171144A1 (ru) * | 2009-03-19 | 2012-04-30 | Мерк Шарп Энд Домэ Корп. | ОПОСРЕДОВАННОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНА ГОМОЛОГА 1 BTB И CNC, ОСНОВНОГО ФАКТОРА ТРАНСКРИПЦИИ С ЛЕЙЦИНОВОЙ МОЛНИЕЙ 1 (Bach1) С ИСПОЛЬЗОВАНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК) |
CN102378766A (zh) | 2009-03-23 | 2012-03-14 | 夸克医药公司 | 治疗癌症和纤维化疾病的化合物组合物和方法 |
US20100239632A1 (en) | 2009-03-23 | 2010-09-23 | Warsaw Orthopedic, Inc. | Drug depots for treatment of pain and inflammation in sinus and nasal cavities or cardiac tissue |
WO2010120874A2 (en) | 2009-04-14 | 2010-10-21 | Chimeros, Inc. | Chimeric therapeutics, compositions, and methods for using same |
US8815586B2 (en) * | 2009-04-24 | 2014-08-26 | 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 |
US8367350B2 (en) | 2009-04-29 | 2013-02-05 | Morehouse School Of Medicine | Compositions and methods for diagnosis, prognosis and management of malaria |
WO2010128465A1 (en) | 2009-05-05 | 2010-11-11 | Beeologics, Llc | Prevention and treatment of nosema disease in bees |
US8933049B2 (en) * | 2009-05-05 | 2015-01-13 | Medical Diagnostic Laboratories, Llc | Repressor on IFN-λ promoter and siRNA against ZEB1 and BLIMP-1 to increase IFN-λ gene activity |
US9255266B2 (en) | 2009-05-06 | 2016-02-09 | Rutgers, The State University Of New Jersey | RNA targeting in alpha-synucleinopathies |
MX2011011395A (es) * | 2009-05-15 | 2011-11-18 | Hoffmann La Roche | Composiciones y metodos para inhibir la expresion de genes de receptor de glucocorticoide. |
CA2762524A1 (en) * | 2009-05-18 | 2011-01-13 | Ensysce Biosciences, Inc. | Carbon nanotubes complexed with multiple bioactive agents and methods related thereto |
EP2432499A2 (en) | 2009-05-20 | 2012-03-28 | Schering Corporation | Modulation of pilr receptors to treat microbial infections |
WO2010135669A1 (en) * | 2009-05-22 | 2010-11-25 | Sabiosciences Corporation | Arrays and methods for reverse genetic functional analysis |
CA2764158A1 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
US20120083519A1 (en) * | 2009-06-03 | 2012-04-05 | Djillali Sahali | Methods For Diagnosing And Treating A Renal Disease In An Individual |
US9187757B2 (en) | 2009-06-05 | 2015-11-17 | University Of Florida Research Foundation, Inc. | Isolation and targeted suppression of lignin biosynthetic genes |
CN102458418B (zh) | 2009-06-08 | 2015-09-16 | 夸克制药公司 | 一种寡核苷酸化合物的制药用途 |
AU2010259295B2 (en) | 2009-06-10 | 2015-05-07 | Temasek Life Sciences Laboratory Limited | Virus induced gene silencing (VIGS) for functional analysis of genes in cotton. |
SG10201912450XA (en) | 2009-06-10 | 2020-03-30 | Arbutus Biopharma Corp | Improved lipid formulation |
US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
CN104651408A (zh) | 2009-06-15 | 2015-05-27 | 阿尔尼拉姆医药品有限公司 | 靶向pcsk9基因的脂质配制的dsrna |
US20100324124A1 (en) * | 2009-06-17 | 2010-12-23 | Massachusetts Institute Of Technology | Compositions and methods relating to DNA-based particles |
US20100323018A1 (en) * | 2009-06-17 | 2010-12-23 | Massachusetts Institute Of Technology | Branched DNA/RNA monomers and uses thereof |
GB0910723D0 (en) * | 2009-06-22 | 2009-08-05 | Sylentis Sau | Novel drugs for inhibition of gene expression |
JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
US8569256B2 (en) | 2009-07-01 | 2013-10-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
EP2454371B1 (en) | 2009-07-13 | 2021-01-20 | Somagenics, Inc. | Chemical modification of small hairpin rnas for inhibition of gene expression |
US8716464B2 (en) * | 2009-07-20 | 2014-05-06 | Thomas W. Geisbert | Compositions and methods for silencing Ebola virus gene expression |
PL2769737T3 (pl) | 2009-07-20 | 2017-08-31 | Bristol-Myers Squibb Company | Kombinacja przeciwciała anty-ctla-4 z etopozydem w leczeniu synergicznym chorób proliferacyjnych |
AU2010282340B2 (en) | 2009-08-13 | 2016-12-22 | The Johns Hopkins University | Methods of modulating immune function |
EP2810643A3 (en) | 2009-08-14 | 2015-03-11 | Alnylam Pharmaceuticals Inc. | Lipid formulated compositions and mehods for inhibiting expression of a gene from the ebola virus |
CA2772036A1 (en) | 2009-08-24 | 2011-03-03 | Phigenix, Inc. | Targeting pax2 for the treatment of breast cancer |
ES2655079T3 (es) | 2009-09-10 | 2018-02-16 | Merck Sharp & Dohme Corp. | Uso de antagonistas de IL-33 para tratar enfermedades fibróticas |
EP2295543A1 (en) | 2009-09-11 | 2011-03-16 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Method for the preparation of an influenza virus |
WO2011032100A1 (en) | 2009-09-11 | 2011-03-17 | Government Of The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Inhibitors of kshv vil6 and human il6 |
CN107519133A (zh) | 2009-09-15 | 2017-12-29 | 阿尔尼拉姆医药品有限公司 | 脂质配制的组合物及抑制Eg5和VEGF基因的表达的方法 |
US8916693B2 (en) | 2009-09-17 | 2014-12-23 | Nektar Therapeutics | Monoconjugated chitosans as delivery agents for small interfering nucleic acids |
WO2011038031A1 (en) | 2009-09-22 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Dual targeting sirna agents |
CA2775092A1 (en) * | 2009-09-23 | 2011-03-31 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing genes expressed in cancer |
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 |
US8962584B2 (en) | 2009-10-14 | 2015-02-24 | Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. | Compositions for controlling Varroa mites in bees |
JP5866119B2 (ja) | 2009-10-30 | 2016-02-17 | ノースウェスタン ユニバーシティ | 鋳型ナノ複合体 |
US9101643B2 (en) | 2009-11-03 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of transthyretin (TTR) |
US9799416B2 (en) * | 2009-11-06 | 2017-10-24 | Terrapower, Llc | Methods and systems for migrating fuel assemblies in a nuclear fission reactor |
US8901097B2 (en) | 2009-11-08 | 2014-12-02 | Quark Pharmaceuticals, Inc. | Methods for delivery of siRNA to the spinal cord and therapies arising therefrom |
US9260517B2 (en) | 2009-11-17 | 2016-02-16 | Musc Foundation For Research Development | Human monoclonal antibodies to human nucleolin |
ES2759003T3 (es) | 2009-11-26 | 2020-05-07 | Quark Pharmaceuticals Inc | Compuestos de ARNip que comprenden sustituciones terminales |
EP2509636B1 (en) | 2009-12-07 | 2017-07-19 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
EP2510098B1 (en) | 2009-12-09 | 2015-02-11 | Quark Pharmaceuticals, Inc. | Methods and compositions for treating diseases, disorders or injury of the cns |
CN102741410B (zh) * | 2009-12-09 | 2016-11-16 | 日东电工株式会社 | Hsp47表达的调节 |
US8785371B2 (en) | 2009-12-10 | 2014-07-22 | Cedars-Sinai Medical Center | Drug delivery of temozolomide for systemic based treatment of cancer |
EP2336171A1 (en) | 2009-12-11 | 2011-06-22 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Novel targets for the treatment of proliferative diseases |
US8691227B2 (en) | 2009-12-17 | 2014-04-08 | Merck Sharp & Dohme Corp. | Methods of treating multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease using agonists antibodies to PILR-α |
MX369004B (es) | 2009-12-18 | 2019-10-24 | Novartis Ag | Composiciones orgánicas para tratar las enfermedades relacionadas con hsf1. |
WO2011075656A1 (en) | 2009-12-18 | 2011-06-23 | The University Of British Columbia | Methods and compositions for delivery of nucleic acids |
WO2011076873A1 (en) | 2009-12-23 | 2011-06-30 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Influenza targets |
JP5553906B2 (ja) | 2009-12-23 | 2014-07-23 | グラダリス インク. | フューリンノックダウン及びgm−csf増強(fang)癌ワクチン |
US20130023578A1 (en) | 2009-12-31 | 2013-01-24 | Samyang Biopharmaceuticals Corporation | siRNA for inhibition of c-Met expression and anticancer composition containing the same |
WO2011084193A1 (en) | 2010-01-07 | 2011-07-14 | Quark Pharmaceuticals, Inc. | Oligonucleotide compounds comprising non-nucleotide overhangs |
TW201124159A (en) * | 2010-01-07 | 2011-07-16 | Univ Nat Cheng Kung | Small interference RNA molecule and applications thereof |
DK2524039T3 (en) * | 2010-01-11 | 2018-03-12 | Curna Inc | TREATMENT OF GENDER HORMON-BINDING GLOBULIN (SHBG) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENCE TRANSCRIPTS TO SHBG |
WO2011088058A1 (en) * | 2010-01-12 | 2011-07-21 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expressions of factor vii and pten genes |
DE102010004957A1 (de) | 2010-01-14 | 2011-07-21 | Universitätsklinikum Jena, 07743 | Biologisch wirksame Moleküle zur Beeinflussung von Virus-, Bakterien-, Parasiten-infizierten Zellen und/oder Tumorzellen und Verfahren zu deren Anwendung |
US9198972B2 (en) | 2010-01-28 | 2015-12-01 | Alnylam Pharmaceuticals, Inc. | Monomers and oligonucleotides comprising cycloaddition adduct(s) |
WO2011094580A2 (en) | 2010-01-28 | 2011-08-04 | Alnylam Pharmaceuticals, Inc. | Chelated copper for use in the preparation of conjugated oligonucleotides |
US8722641B2 (en) | 2010-01-29 | 2014-05-13 | St. Jude Children's Research Hospital | Oligonucleotides which inhibit p53 induction in response to cellular stress |
AU2011214465A1 (en) | 2010-02-10 | 2012-08-30 | Novartis Ag | Methods and compounds for muscle growth |
US9186370B2 (en) * | 2010-03-19 | 2015-11-17 | University Of South Alabama | Methods and compositions for the treatment of cancer |
WO2011119871A1 (en) | 2010-03-24 | 2011-09-29 | Rxi Phrmaceuticals Corporation | Rna interference in ocular indications |
US9080171B2 (en) | 2010-03-24 | 2015-07-14 | RXi Parmaceuticals Corporation | Reduced size self-delivering RNAi compounds |
CN110042099A (zh) | 2010-03-24 | 2019-07-23 | 菲奥医药公司 | 皮肤与纤维化症候中的rna干扰 |
US8455455B1 (en) | 2010-03-31 | 2013-06-04 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing genes involved in hemorrhagic fever |
US9102938B2 (en) | 2010-04-01 | 2015-08-11 | Alnylam Pharmaceuticals, Inc. | 2′ and 5′ modified monomers and oligonucleotides |
WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
WO2011133868A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Conformationally restricted dinucleotide monomers and oligonucleotides |
WO2011133658A1 (en) | 2010-04-22 | 2011-10-27 | Boston Medical Center Corporation | Compositions and methods for targeting and delivering therapeutics into cells |
WO2011133871A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | 5'-end derivatives |
CA2994063A1 (en) | 2010-04-29 | 2011-11-10 | Ionis Pharmaceuticals, Inc. | Modulation of transthyretin expression |
WO2011137363A1 (en) | 2010-04-30 | 2011-11-03 | Allergan, Inc. | Novel treatment for age related macular degeneration and ocular ischemic disease associated with complement activation by targeting 5-lipoxygenase |
ES2596431T3 (es) | 2010-05-04 | 2017-01-09 | The Brigham And Women's Hospital, Inc. | Antagonista de cadherina-11 para el tratamiento de fibrosis |
US8563243B2 (en) * | 2010-05-12 | 2013-10-22 | University Of South Carolina | Methods for affecting homology-directed DNA double stranded break repair |
BR112012029912A2 (pt) | 2010-05-26 | 2016-11-16 | Selecta Biosciences Inc | vácinas de combinação de nanotransportadores sintéticos |
EP2390327A1 (en) | 2010-05-27 | 2011-11-30 | Sylentis S.A. | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
DE102010022937A1 (de) | 2010-06-04 | 2011-12-08 | Universitätsklinikum Jena | Zellspezifisch aktivierbare biologisch wirksame Moleküle auf Grundlage von siRNA, Verfahren zu deren Aktivierung sowie Applikationskit zur Verabreichung |
WO2011163121A1 (en) | 2010-06-21 | 2011-12-29 | Alnylam Pharmaceuticals, Inc. | Multifunctional copolymers for nucleic acid delivery |
KR101553753B1 (ko) | 2010-06-24 | 2015-09-16 | 쿠아크 파마수티칼스 인코퍼레이티드 | Rhoa에 대한 이중 가닥 rna 및 그의 용도 |
US9006417B2 (en) | 2010-06-30 | 2015-04-14 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
US20130323269A1 (en) | 2010-07-30 | 2013-12-05 | Muthiah Manoharan | Methods and compositions for delivery of active agents |
US20130202652A1 (en) | 2010-07-30 | 2013-08-08 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
WO2012019132A2 (en) | 2010-08-06 | 2012-02-09 | Cell Signaling Technology, Inc. | Anaplastic lymphoma kinase in kidney cancer |
CN103140582A (zh) | 2010-08-24 | 2013-06-05 | 默沙东公司 | 含有内部非核酸间隔子的单链RNAi试剂 |
WO2012041959A1 (en) | 2010-09-30 | 2012-04-05 | University Of Zurich | Treatment of b-cell lymphoma with microrna |
US20140315973A1 (en) * | 2010-10-07 | 2014-10-23 | Agency For Science, Technology And Research | Parp-1 inhibitors |
WO2012051491A1 (en) | 2010-10-14 | 2012-04-19 | The United States Of America, As Represented By The Secretary National Institutes Of Health | Compositions and methods for controlling neurotropic viral pathogenesis by micro-rna targeting |
ES2732929T3 (es) * | 2010-10-22 | 2019-11-26 | Olix Pharmaceuticals Inc | Moléculas de ácido nucleico que inducen interferencia de ARN y usos de las mismas |
EP3327125B1 (en) | 2010-10-29 | 2020-08-05 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
WO2012071436A1 (en) | 2010-11-24 | 2012-05-31 | Genentech, Inc. | Method of treating autoimmune inflammatory disorders using il-23r loss-of-function mutants |
CN103298939A (zh) | 2010-12-06 | 2013-09-11 | 夸克医药公司 | 包含位置修饰的双链寡核苷酸化合物 |
US10202615B2 (en) | 2010-12-10 | 2019-02-12 | Vanderbilt University | Mammalian genes involved in toxicity and infection |
US9617542B2 (en) * | 2010-12-14 | 2017-04-11 | The United States of America, as representd by The Secretary of Agriculture | Lepidopteran moth control using double-stranded RNA constructs |
US9623041B2 (en) | 2010-12-30 | 2017-04-18 | Cedars-Sinai Medical Center | Polymalic acid-based nanobiopolymer compositions |
ES2808529T3 (es) | 2011-01-10 | 2021-03-01 | Univ Michigan Regents | Inhibidor del factor de células madre |
US20150018408A1 (en) | 2013-07-10 | 2015-01-15 | The Regents Of The University Of Michigan | Therapeutic antibodies and uses thereof |
CA2824526C (en) | 2011-01-11 | 2020-07-07 | Alnylam Pharmaceuticals, Inc. | Pegylated lipids and their use for drug delivery |
DE102011009470A1 (de) | 2011-01-21 | 2012-08-09 | Friedrich-Schiller-Universität Jena | Biologisch wirksame Nukleotid-Moleküle zur gezielten Abtötung von Zellen, Verwendung derselben sowie Applikationskit |
PT2670411T (pt) | 2011-02-02 | 2019-06-18 | Excaliard Pharmaceuticals Inc | Compostos anti sentido visando um fator de crescimento do tecido conetivo (ctfg) para utilização num método de tratamento de queloides ou cicatrizes hipertróficas |
WO2012106586A1 (en) | 2011-02-03 | 2012-08-09 | Mirna Therapeutics, Inc. | Synthetic mimics of mir-124 |
CA2828544A1 (en) * | 2011-03-03 | 2012-09-07 | 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 |
WO2012125554A2 (en) * | 2011-03-11 | 2012-09-20 | Board Of Regents Of The University Of Nebraska | Compositions and methods for the treatment of cancer |
CN103562408A (zh) | 2011-03-15 | 2014-02-05 | 犹他大学研究基金会 | 诊断和治疗血管相关黄斑病及其症状的方法 |
US9458456B2 (en) * | 2011-04-01 | 2016-10-04 | University Of South Alabama | Methods and compositions for the diagnosis, classification, and treatment of cancer |
AU2012242784B2 (en) | 2011-04-12 | 2017-04-13 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Peptide mimetic ligands of polo-like kinase 1 polo box domain and methods of use |
WO2012142458A1 (en) | 2011-04-13 | 2012-10-18 | Isis Pharmaceuticals, Inc. | Antisense modulation of ptp1b expression |
US8716257B2 (en) * | 2011-04-15 | 2014-05-06 | Sutter West Bay Hospitals | CMV gene products promote cancer stem cell growth |
EP2696678B1 (en) * | 2011-04-15 | 2019-11-20 | Molecular Transfer, Inc. | Agents for improved delivery of nucleic acids to eukaryotic cells |
MX2013013329A (es) | 2011-05-20 | 2014-04-16 | Us Government | Bloqueo de interacciones de factor de necrosis tumoral como ligando 1a - receptor de muerte 3 (tl1a-dr3) para mejorar la patologia mediada por las celulas t y los anticuerpos para los mismos. |
PT3446714T (pt) | 2011-06-02 | 2021-06-23 | Univ Louisville Res Found Inc | Nanopartículas conjugadas a um agente antinucleolina |
CN103890000B (zh) * | 2011-06-21 | 2017-09-01 | 阿尔尼拉姆医药品有限公司 | 血管生成素样3(ANGPTL3)iRNA组合物及其使用方法 |
EP2723861A4 (en) | 2011-06-21 | 2014-12-10 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR INHIBITING HEPCIDINE ANTIMICROBIAL PEPTIDE (HAMP) OR THE ASSOCIATED GENE EXPRESSION |
US9068184B2 (en) | 2011-06-21 | 2015-06-30 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibition of expression of protein C (PROC) genes |
KR102369777B1 (ko) | 2011-06-21 | 2022-03-03 | 알닐람 파마슈티칼스 인코포레이티드 | 아포리포단백질 c-iii(apoc3) 유전자의 발현 억제를 위한 조성물 및 방법 |
US20140227293A1 (en) | 2011-06-30 | 2014-08-14 | Trustees Of Boston University | Method for controlling tumor growth, angiogenesis and metastasis using immunoglobulin containing and proline rich receptor-1 (igpr-1) |
WO2013001372A2 (en) | 2011-06-30 | 2013-01-03 | University Of Oslo | Methods and compositions for inhibition of activation of regulatory t cells |
SI2729173T1 (sl) | 2011-07-06 | 2016-10-28 | Sykehuset Sorlandet Hf | Terapija, ki cilja na EGFR |
WO2013006861A1 (en) | 2011-07-07 | 2013-01-10 | University Of Georgia Research Foundation, Inc. | Sorghum grain shattering gene and uses thereof in altering seed dispersal |
US8853181B2 (en) | 2011-07-21 | 2014-10-07 | Albert Einstein College Of Medicine Of Yeshiva University | Fidgetin-like 2 as a target to enhance wound healing |
US9120858B2 (en) | 2011-07-22 | 2015-09-01 | The Research Foundation Of State University Of New York | Antibodies to the B12-transcobalamin receptor |
DE102011118024A1 (de) | 2011-08-01 | 2013-02-07 | Technische Universität Dresden | Inhibitor der Expression der Pro-Caspase 1 |
ES2651515T3 (es) | 2011-09-06 | 2018-01-26 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | La familia miARN-212/132 como diana terapéutica |
EP2747774A4 (en) | 2011-09-09 | 2015-02-11 | Biomed Realty L P | METHOD AND COMPOSITIONS FOR CONTROLLING VIRUS PROTECTION |
US9644241B2 (en) | 2011-09-13 | 2017-05-09 | Interpace Diagnostics, Llc | Methods and compositions involving miR-135B for distinguishing pancreatic cancer from benign pancreatic disease |
WO2013049389A1 (en) | 2011-09-27 | 2013-04-04 | Yale University | Compositions and methods for transient expression of recombinant rna |
US9701623B2 (en) | 2011-09-27 | 2017-07-11 | Alnylam Pharmaceuticals, Inc. | Di-aliphatic substituted pegylated lipids |
EP3597644B1 (en) | 2011-10-18 | 2021-09-29 | Dicerna Pharmaceuticals, Inc. | Amine cationic lipids and uses thereof |
EP2776565A1 (en) | 2011-11-08 | 2014-09-17 | Quark Pharmaceuticals, Inc. | Methods and compositions for treating diseases, disorders or injury of the nervous system |
EP2725103A3 (en) * | 2011-11-14 | 2016-01-06 | Silenseed Ltd | Methods and compositions for treating prostate cancer |
IL293434B2 (en) | 2011-11-18 | 2024-05-01 | Alnylam Pharmaceuticals Inc | RNAI factors, preparations and methods of using them for the treatment of transthyretin-related diseases |
WO2013082529A1 (en) | 2011-12-02 | 2013-06-06 | Yale University | Enzymatic synthesis of poly(amine-co-esters) and methods of use thereof for gene delivery |
WO2013098813A1 (en) | 2012-01-01 | 2013-07-04 | Qbi Enterprises Ltd. | Endo180-targeted particles for selective delivery of therapeutic and diagnostic agents |
WO2013103401A1 (en) * | 2012-01-06 | 2013-07-11 | University Of South Alabama | Methods and compositions for the treatment of cancer |
JP6158833B2 (ja) | 2012-01-09 | 2017-07-05 | アローヘッド ファーマシューティカルズ インコーポレイテッド | ベータ−カテニン関連疾患を処置するための有機組成物 |
BR112014016937A2 (pt) | 2012-01-12 | 2017-06-13 | Quark Pharmaceuticals Inc | terapia de combinação para o tratamento de desordens de audição e do equilíbrio |
US20150126438A1 (en) | 2012-01-24 | 2015-05-07 | Beth Israel Deaconess Medical Center, Inc. | Novel ChREBP Isoforms and Methods Using the Same |
WO2013138456A1 (en) | 2012-03-14 | 2013-09-19 | University Of Central Florida Research Foundation, Inc. | Lim kinasemodulating agents for neurofibromatoses therapy and methods for screening for same |
KR20140136488A (ko) | 2012-03-15 | 2014-11-28 | 큐알엔에이, 인크. | 뇌 유래 신경영양 인자(bdnf)에 대한 천연 안티센스 전사체의 저해에 의한 뇌 유래 신경영양 인자(bdnf)관련 질환의 치료 |
WO2013158859A1 (en) | 2012-04-18 | 2013-10-24 | Cell Signaling Technology, Inc. | Egfr and ros1 in cancer |
US9980942B2 (en) | 2012-05-02 | 2018-05-29 | Children's Hospital Medical Center | Rejuvenation of precursor cells |
WO2013165816A2 (en) | 2012-05-02 | 2013-11-07 | Merck Sharp & Dohme Corp. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
EP2853597B1 (en) | 2012-05-22 | 2018-12-26 | Olix Pharmaceuticals, Inc. | Rna-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor |
EP2867368B1 (en) | 2012-07-06 | 2022-01-12 | Institut Gustave Roussy | Simultaneous detection of cannibalism and senescence as prognostic marker for cancer |
WO2014018375A1 (en) | 2012-07-23 | 2014-01-30 | Xenon Pharmaceuticals Inc. | Cyp8b1 and uses thereof in therapeutic and diagnostic methods |
EP2890788A1 (en) * | 2012-08-31 | 2015-07-08 | The General Hospital Corporation | Biotin complexes for treatment and diagnosis of alzheimer's disease |
GB201215857D0 (en) | 2012-09-05 | 2012-10-24 | Sylentis Sau | siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions |
CN104781402A (zh) | 2012-09-05 | 2015-07-15 | 西伦蒂斯私人股份公司 | siRNA及其在用于治疗和/或预防眼部病症的方法和组合物中的应用 |
BR112015004747A2 (pt) | 2012-09-12 | 2017-11-21 | Quark Pharmaceuticals Inc | moléculas oligonucleotídicas de fita dupla para p53 e métodos de uso das mesmas |
DK2895608T3 (en) | 2012-09-12 | 2019-01-21 | Quark Pharmaceuticals Inc | DOUBLE-STRENGTHED OIGONUCLEOTIDE MOLECULES FOR P53 AND PROCEDURES FOR USING IT |
KR101839864B1 (ko) | 2012-09-21 | 2018-03-20 | 인텐시티 쎄라퓨틱스, 인코포레이티드 | 암을 치료하는 방법 |
WO2014055624A1 (en) * | 2012-10-02 | 2014-04-10 | The General Hospital Corporation D/B/A Massachusetts General Hospital | Methods relating to dna-sensing pathway related conditions |
WO2014055825A1 (en) | 2012-10-04 | 2014-04-10 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | A formulation of mycobacterial components as an adjuvant for inducing th17 responses |
WO2014068072A1 (en) | 2012-10-31 | 2014-05-08 | Institut Gustave-Roussy | Identification, assessment and therapy of essential thrombocythemia with resistance to jak2 inhibitors |
CN105051192B (zh) | 2012-11-13 | 2020-04-17 | 科迪艾克生物科学公司 | 治疗剂的递送 |
CA2891673A1 (en) | 2012-11-15 | 2014-05-22 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods |
DE102012022596B4 (de) | 2012-11-15 | 2017-05-04 | Friedrich-Schiller-Universität Jena | Neue zellspezifisch wirksame Nukleotid-Moleküle und Applikationskit zu deren Anwendung |
BR112015011995B1 (pt) | 2012-11-27 | 2023-02-07 | Children's Medical Center Corporation | Método para a produção de uma célula progenitora hematopoiética tendo bcl11a diminuído ou para aumentar seus níveis de hemoglobina fetal, composição e uso das mesmas |
WO2014093688A1 (en) | 2012-12-12 | 2014-06-19 | 1Massachusetts Institute Of Technology | Compositions and methods for functional nucleic acid delivery |
US20150320861A1 (en) | 2012-12-21 | 2015-11-12 | Sykehuset Sørlandet Hf | Egfr targeted therapy of neurological disorders and pain |
US9206423B2 (en) * | 2012-12-30 | 2015-12-08 | The Regents Of The University Of California | Methods of modulating compliance of the trabecular meshwork |
WO2014113541A1 (en) | 2013-01-16 | 2014-07-24 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Attenuated chlamydia vaccine |
DE102013003869B4 (de) | 2013-02-27 | 2016-11-24 | Friedrich-Schiller-Universität Jena | Verfahren zur gezielten Abtötung von Zellen durch zur mRNA-Anbindung ausgerichtete Nukleotid-Moleküle sowie Nukleotid-Moleküle und Applikationskit für solche Verwendung |
WO2014153163A1 (en) | 2013-03-14 | 2014-09-25 | Dicerna Pharmaceuticals, Inc. | Process for formulating an anionic agent |
WO2014152391A1 (en) | 2013-03-15 | 2014-09-25 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
US9850543B2 (en) * | 2013-03-15 | 2017-12-26 | Novartis Ag | Biomarkers associated with BRM inhibition |
WO2014144721A2 (en) * | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Treating th2-mediated diseases by inhibition of bromodomains |
EP2978446B1 (en) | 2013-03-27 | 2020-03-04 | The General Hospital Corporation | Anti-cd33 antibody for use in treating alzheimer's disease |
CA2912801A1 (en) | 2013-05-17 | 2014-11-20 | Medimmune, Llc | Receptors for b7-h4 |
CA2916533C (en) | 2013-06-25 | 2022-12-20 | University Of Canberra | Methods and compositions for modulating cancer stem cells |
TW201534578A (zh) | 2013-07-08 | 2015-09-16 | Daiichi Sankyo Co Ltd | 新穎脂質 |
BR112016000555B1 (pt) | 2013-07-19 | 2022-12-27 | Monsanto Technology Llc | Método para controlar uma infestação da espécie de leptinotarsa em uma planta, composição inseticida e construção de dna recombinante |
US10711106B2 (en) | 2013-07-25 | 2020-07-14 | The University Of Chicago | High aspect ratio nanofibril materials |
EP3027222A1 (en) | 2013-07-31 | 2016-06-08 | QBI Enterprises Ltd. | Sphingolipid-polyalkylamine-oligonucleotide compounds |
WO2015015498A1 (en) | 2013-07-31 | 2015-02-05 | Qbi Enterprises Ltd. | Methods of use of sphingolipid polyalkylamine oligonucleotide compounds |
ES2790574T3 (es) * | 2013-08-28 | 2020-10-28 | Ionis Pharmaceuticals Inc | Modulación de expresión de prekallikrein (PKK) |
CA2923859C (en) | 2013-09-11 | 2021-11-23 | Arsia Therapeutics, Inc. | Liquid protein formulations containing viscosity-lowering agents |
SG11201601408PA (en) | 2013-09-18 | 2016-04-28 | Univ Canberra | Stem cell modulation ii |
AU2014329560B2 (en) | 2013-10-04 | 2017-03-02 | Novartis Ag | 3'end caps for RNAi agents for use in RNA interference |
CN105792832B (zh) | 2013-10-04 | 2021-03-23 | 诺华股份有限公司 | 用于治疗乙肝病毒的有机化合物 |
EP2865758A1 (en) | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the ORAI1 gene |
EP2865756A1 (en) | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the FLAP gene. |
EP2865757A1 (en) | 2013-10-22 | 2015-04-29 | Sylentis, S.A.U. | siRNA and their use in methods and compositions for inhibiting the expression of the PDK1 gene. |
WO2015070158A1 (en) | 2013-11-11 | 2015-05-14 | Sirna Therapeutics, Inc. | Systemic delivery of myostatin short interfering nucleic acids (sina) conjugated to a lipophilic moiety |
EP3071590A4 (en) | 2013-11-21 | 2017-07-19 | SeNA Research, Inc. | Methods for structural determination of selenium derivatized nucleic acid complexes |
EP3079707A4 (en) | 2013-12-02 | 2017-10-18 | RXi Pharmaceuticals Corporation | Immunotherapy of cancer |
AU2014360314B2 (en) | 2013-12-06 | 2018-04-26 | Dicerna Pharmaceuticals, Inc. | Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA |
CN104830906B (zh) | 2014-02-12 | 2018-09-04 | 北京维通达生物技术有限公司 | 一种重编程获得功能性人肝脏实质细胞的方法 |
US10011837B2 (en) | 2014-03-04 | 2018-07-03 | Sylentis Sau | SiRNAs and their use in methods and compositions for the treatment and/or prevention of eye conditions |
PL3116902T3 (pl) | 2014-03-11 | 2020-07-27 | Cellectis | Sposób wytwarzania limfocytów T kompatybilnych do przeszczepienia alogenicznego |
WO2015140330A1 (en) * | 2014-03-20 | 2015-09-24 | Oommen Varghese | Improved small interfering ribonucleic acid molecules |
JP6771387B2 (ja) | 2014-03-25 | 2020-10-21 | アークトゥラス・セラピューティクス・インコーポレイテッドArcturus Therapeutics,Inc. | 遺伝子サイレンシング用トランスサイレチン対立遺伝子選択的unaオリゴマー |
CA2946719C (en) | 2014-03-25 | 2023-09-26 | Arcturus Therapeutics, Inc. | Una oligomers having reduced off-target effects in gene silencing |
US9856475B2 (en) | 2014-03-25 | 2018-01-02 | Arcturus Therapeutics, Inc. | Formulations for treating amyloidosis |
BR112016022711A2 (pt) | 2014-04-01 | 2017-10-31 | Monsanto Technology Llc | composições e métodos para controle de pragas de inseto |
KR20210097225A (ko) | 2014-04-01 | 2021-08-06 | 바이오젠 엠에이 인코포레이티드 | Sod-1 발현을 조절하기 위한 조성물 |
JP6514717B2 (ja) | 2014-04-25 | 2019-05-15 | ザ チルドレンズ メディカル センター コーポレーション | 異常ヘモグロビン症を治療するための組成物および方法 |
EP3137119B1 (en) | 2014-04-28 | 2020-07-01 | Phio Pharmaceuticals Corp. | Methods for treating cancer using a nucleic acid targeting mdm2 |
BR112016022855B1 (pt) | 2014-05-01 | 2022-08-02 | Ionis Pharmaceuticals, Inc | Compostos e composições para modular a expressão de pkk e seus usos |
AU2015252805B2 (en) | 2014-05-02 | 2018-05-10 | Research Institute At Nationwide Children's Hospital | Compositions and methods for anti-LYST immunomodulation |
US10335500B2 (en) | 2014-05-12 | 2019-07-02 | The Johns Hopkins University | Highly stable biodegradable gene vector platforms for overcoming biological barriers |
WO2015175539A1 (en) | 2014-05-12 | 2015-11-19 | The Johns Hopkins University | Engineering synthetic brain penetrating gene vectors |
WO2015184105A1 (en) | 2014-05-29 | 2015-12-03 | Trustees Of Dartmouth College | Method for selectively inhibiting acat1 in the treatment of neurodegenerative diseases |
ES2725948T3 (es) | 2014-06-04 | 2019-09-30 | Exicure Inc | Suministro multivalente de inmunomoduladores mediante ácidos nucleicos esféricos liposomales para aplicaciones profilácticas o terapéuticas |
CN104120127B (zh) * | 2014-07-01 | 2016-09-21 | 清华大学 | 分离的寡核苷酸及其应用 |
CA2955842A1 (en) | 2014-07-29 | 2016-02-04 | Monsanto Technology Llc | Compositions and methods for controlling insect pests |
WO2016019126A1 (en) | 2014-07-30 | 2016-02-04 | The Research Foundation For The State University Of New York | System and method for delivering genetic material or protein to cells |
DE112015003749A5 (de) | 2014-08-14 | 2018-01-11 | Friedrich-Schiller-Universität Jena | Peptid zur verwendung in der reduktion von nebenwirkungen in form von immunstimulatorischen reaktionen/effekten |
US10485772B2 (en) | 2014-08-25 | 2019-11-26 | EpiAxis Therapeutics Pty Ltd. | Compositions for modulating cancer stem cells and uses therefor |
PT3185957T (pt) | 2014-08-29 | 2022-09-05 | Alnylam Pharmaceuticals Inc | Patisiran para utilização no tratamento de amoloidose mediada por transtirretina |
EP3188799B1 (en) | 2014-09-05 | 2022-07-06 | Phio Pharmaceuticals Corp. | Methods for treating aging and skin disorders using nucleic acids targeting tyr or mmp1 |
WO2016044271A2 (en) | 2014-09-15 | 2016-03-24 | Children's Medical Center Corporation | Methods and compositions to increase somatic cell nuclear transfer (scnt) efficiency by removing histone h3-lysine trimethylation |
JP2017531629A (ja) | 2014-09-25 | 2017-10-26 | コールド スプリング ハーバー ラボラトリー | レット症候群の処置 |
US11471479B2 (en) | 2014-10-01 | 2022-10-18 | Eagle Biologics, Inc. | Polysaccharide and nucleic acid formulations containing viscosity-lowering agents |
JOP20200115A1 (ar) | 2014-10-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات وطرق لتثبيط التعبير الجيني عن hao1 (حمض أوكسيداز هيدروكسيلي 1 (أوكسيداز جليكولات)) |
WO2016057693A1 (en) | 2014-10-10 | 2016-04-14 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for inhalation delivery of conjugated oligonucleotide |
CA2964155A1 (en) | 2014-10-10 | 2016-04-14 | Idera Pharmaceuticals, Inc. | Treatment of cancer using tlr9 agonist with checkpoint inhibitors |
US10538762B2 (en) | 2014-10-14 | 2020-01-21 | The Board Of Regents Of The University Of Texas System | Allele selective inhibition of mutant C9orf72 foci expression by duplex RNAS targeting the expanded hexanucleotide repeat |
AU2015336954A1 (en) | 2014-10-22 | 2017-06-08 | Katholieke Universiteit Leuven Ku Leuven Research & Development | Modulating adipose tissue and adipogenesis |
JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
WO2016077624A1 (en) | 2014-11-12 | 2016-05-19 | Nmc, Inc. | Transgenic plants with engineered redox sensitive modulation of photosynthetic antenna complex pigments and methods for making the same |
CN107250362B (zh) | 2014-11-17 | 2021-10-22 | 阿尔尼拉姆医药品有限公司 | 载脂蛋白C3(APOC3)iRNA组合物及其使用方法 |
WO2016081621A1 (en) | 2014-11-18 | 2016-05-26 | Yale University | Formulations for targeted release of agents under low ph conditions and methods of use thereof |
CN107106493A (zh) | 2014-11-21 | 2017-08-29 | 西北大学 | 球形核酸纳米颗粒缀合物的序列特异性细胞摄取 |
US20190002876A1 (en) * | 2014-12-09 | 2019-01-03 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treatment of friedreich's ataxia |
US20180002702A1 (en) * | 2014-12-26 | 2018-01-04 | Nitto Denko Corporation | Methods and compositions for treating malignant tumors associated with kras mutation |
US10792299B2 (en) | 2014-12-26 | 2020-10-06 | Nitto Denko Corporation | Methods and compositions for treating malignant tumors associated with kras mutation |
US10264976B2 (en) | 2014-12-26 | 2019-04-23 | The University Of Akron | Biocompatible flavonoid compounds for organelle and cell imaging |
UA124255C2 (uk) | 2015-01-22 | 2021-08-18 | Монсанто Текнолоджі Елелсі | Інсектицидна композиція та спосіб боротьби з leptinotarsa |
US10519447B2 (en) | 2015-04-01 | 2019-12-31 | Arcturus Therapeutics, Inc. | Therapeutic UNA oligomers and uses thereof |
IL254786B (en) | 2015-04-13 | 2022-09-01 | Alnylam Pharmaceuticals Inc | Preparations of angiopoietin-like 3 irna and methods of using them |
WO2016168197A1 (en) | 2015-04-15 | 2016-10-20 | Yale University | Compositions for enhancing delivery of agents across the blood brain barrier and methods of use thereof |
CA3020885A1 (en) | 2015-05-05 | 2016-11-10 | Mohammad Tariq MALIK | Anti-nucleolin agent-conjugated nanoparticles as radio-sensitizers and mri and/or x-ray contrast agents |
US11572543B2 (en) | 2015-05-08 | 2023-02-07 | The Children's Medical Center. Corporation | Targeting BCL11A enhancer functional regions for fetal hemoglobin reinduction |
AU2016269839B2 (en) | 2015-06-03 | 2021-07-08 | The University Of Queensland | Mobilizing agents and uses therefor |
KR20180017119A (ko) | 2015-06-10 | 2018-02-20 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 질환의 치료를 위한 엑소좀의 용도 |
EP3318275A4 (en) | 2015-06-30 | 2019-02-06 | Tadamitsu Kishimoto | NOVEL THERAPEUTIC AGENT AGAINST PULMONARY DISEASES AND / OR SCREENING METHOD THEREOF |
WO2017007825A1 (en) | 2015-07-06 | 2017-01-12 | Rxi Pharmaceuticals Corporation | Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach |
CA2991598A1 (en) | 2015-07-06 | 2017-01-12 | Rxi Pharmaceuticals Corporation | Nucleic acid molecules targeting superoxide dismutase 1 (sod1) |
WO2017011276A1 (en) | 2015-07-10 | 2017-01-19 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (dgat2) |
WO2017015671A1 (en) | 2015-07-23 | 2017-01-26 | Arcturus Therapeutics, Inc. | Compositions for treating amyloidosis |
ES2842300T3 (es) | 2015-07-31 | 2021-07-13 | Alnylam Pharmaceuticals Inc | Composiciones de ARNi de transtiretina (TTR) y métodos para su uso para el tratamiento o la prevención de enfermedades asociadas con TTR |
BR112018003784A2 (pt) | 2015-08-24 | 2018-09-25 | Halo-Bio Rnai Therapeutics, Inc. | nanopartículas de polinucleotídeo para a modulação da expressão gênica e sua utilização |
MA44908A (fr) | 2015-09-08 | 2018-07-18 | Sylentis Sau | Molécules d'arnsi et leur utilisation dans des procédés et des compositions pour inhiber l'expression du gène nrarp |
GB201516685D0 (en) * | 2015-09-21 | 2015-11-04 | Varghese Oommen P And Oommen Oommen P | Nucleic acid molecules with enhanced activity |
US10086063B2 (en) | 2015-09-23 | 2018-10-02 | Regents Of The University Of Minnesota | Methods of making and using live attenuated viruses |
JP6991977B2 (ja) | 2015-09-23 | 2022-02-03 | マサチューセッツ インスティテュート オブ テクノロジー | 修飾デンドリマーナノ粒子ワクチン送達用組成物及び方法 |
US10383935B2 (en) | 2015-09-23 | 2019-08-20 | Regents Of The University Of Minnesota | Methods of making and using live attenuated viruses |
CA2997444A1 (en) | 2015-09-29 | 2017-04-06 | Amgen Inc. | Asgr inhibitors for reducing cholesterol levels |
JOP20210043A1 (ar) * | 2015-10-01 | 2017-06-16 | Arrowhead Pharmaceuticals Inc | تراكيب وأساليب لتثبيط تعبير جيني للـ lpa |
EP4349363A3 (en) | 2015-10-07 | 2024-06-19 | Apellis Pharmaceuticals, Inc. | Dosing regimens |
JP2018531037A (ja) | 2015-10-19 | 2018-10-25 | アールエックスアイ ファーマシューティカルズ コーポレーション | 長い非コードrnaを標的とする減少したサイズの自己送達型核酸化合物 |
JP7027311B2 (ja) | 2015-11-16 | 2022-03-01 | オリックス ファーマシューティカルズ,インコーポレーテッド | MyD88又はTLR3を標的とするRNA複合体を使用した加齢黄斑変性の治療 |
WO2017095751A1 (en) | 2015-12-02 | 2017-06-08 | Partikula Llc | Compositions and methods for modulating cancer cell metabolism |
WO2017100193A1 (en) | 2015-12-10 | 2017-06-15 | Fibrogen, Inc. | Methods for treatment of motor neuron diseases |
CA3008788C (en) | 2015-12-18 | 2021-05-25 | Samyang Biopharmaceuticals Corporation | Method for preparing polymeric micelles containing an anionic drug |
BR102017001164A2 (pt) | 2016-01-26 | 2019-03-06 | Embrapa - Empresa Brasileira De Pesquisa Agropecuária | Composições de rna de fita dupla para controle de diaphorina citri e métodos de uso. |
US10478503B2 (en) | 2016-01-31 | 2019-11-19 | University Of Massachusetts | Branched oligonucleotides |
KR20180104692A (ko) | 2016-02-02 | 2018-09-21 | 올릭스 주식회사 | Angpt2 및 pdgfb를 표적화하는 rna 복합체를 사용하는 혈관신생 관련 질환의 치료 |
CN108779463B (zh) | 2016-02-02 | 2022-05-24 | 奥利克斯医药有限公司 | 使用靶向IL4Rα、TRPA1或F2RL1的RNA复合物治疗特应性皮炎和哮喘 |
US20170360815A1 (en) | 2016-02-25 | 2017-12-21 | Applied Biological Laboratories, Inc. | Compositions and methods for protecting against airborne pathogens and irritants |
WO2017147540A1 (en) | 2016-02-25 | 2017-08-31 | Applied Biological Laboratories, Inc. | Compositions and methods for protecting against airborne pathogens and irritants |
EP3420086A1 (en) | 2016-02-26 | 2019-01-02 | Yale University | COMPOSITIONS AND METHODS OF USING piRNAS IN CANCER DIAGNOSTICS AND THERAPEUTICS |
WO2017151623A1 (en) | 2016-03-01 | 2017-09-08 | Alexion Pharmaceuticals, Inc. | Biodegradable activated polymers for therapeutic delivery |
EP3423568A4 (en) | 2016-03-04 | 2019-11-13 | University Of Louisville Research Foundation, Inc. | METHOD AND COMPOSITIONS FOR EX-VIVO REPRODUCTION OF VERY SMALL EMBRYONAL STEM CELLS (VSELS) |
TWI783434B (zh) | 2016-03-07 | 2022-11-11 | 美商愛羅海德製藥公司 | 治療性化合物之標靶性配體 |
US10947317B2 (en) | 2016-03-15 | 2021-03-16 | Mersana Therapeutics, Inc. | NaPi2b-targeted antibody-drug conjugates and methods of use thereof |
MA45469A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques de bêta-caténine et leurs utilisations |
MA45349A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques egfr et leurs utilisations |
MA45470A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Acides nucléiques kras et leurs utilisations |
US20190117799A1 (en) | 2016-04-01 | 2019-04-25 | The Brigham And Women's Hospital, Inc. | Stimuli-responsive nanoparticles for biomedical applications |
MA45328A (fr) | 2016-04-01 | 2019-02-06 | Avidity Biosciences Llc | Compositions acide nucléique-polypeptide et utilisations de celles-ci |
WO2017176894A1 (en) | 2016-04-06 | 2017-10-12 | Ohio State Innovation Foundation | Rna ligand-displaying exosomes for specific delivery of therapeutics to cell by rna nanotechnology |
CA3020487C (en) | 2016-04-11 | 2022-05-31 | Olix Pharmaceuticals, Inc. | Treatment of idiopathic pulmonary fibrosis using rna complexes that target connective tissue growth factor |
RU2755544C2 (ru) * | 2016-04-14 | 2021-09-17 | Бенитек Биофарма Лимитед | Реагенты для лечения окулофарингеальной мышечной дистрофии (OPMD) и их применение |
US11410746B2 (en) | 2016-04-27 | 2022-08-09 | Massachusetts Institute Of Technology | Stable nanoscale nucleic acid assemblies and methods thereof |
WO2017197128A1 (en) | 2016-05-11 | 2017-11-16 | Yale University | Poly(amine-co-ester) nanoparticles and methods of use thereof |
KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
RU2758007C2 (ru) | 2016-06-30 | 2021-10-25 | Онкорус, Инк. | Доставка терапевтических полипептидов посредством псевдотипированных онколитических вирусов |
RU2627179C1 (ru) * | 2016-07-28 | 2017-08-03 | федеральное государственное бюджетное учреждение "Федеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. Гамалеи" Министерства здравоохранения Российской Федерации | ТЕСТ-СИСТЕМА ДЛЯ ОПРЕДЕЛЕНИЯ РНК ИНТЕРФЕРОНА λ, ИНТЕРЛЕЙКИНА IL23 И ПРОТИВОВИРУСНОГО БЕЛКА MxA |
EP3519582A1 (en) | 2016-07-29 | 2019-08-07 | Danmarks Tekniske Universitet | Methods for decoupling cell growth from production of biochemicals and recombinant polypeptides |
EP3496736A4 (en) | 2016-08-03 | 2020-05-13 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | THERAPEUTICS AGAINST TLR9 |
US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
ES2924806T3 (es) | 2016-09-02 | 2022-10-11 | Dicerna Pharmaceuticals Inc | Análogos de 4'-fosfato y oligonucleótidos que comprenden el mismo |
KR102557906B1 (ko) | 2016-09-02 | 2023-07-20 | 애로우헤드 파마슈티컬스 인코포레이티드 | 표적화 리간드 |
WO2018057575A1 (en) | 2016-09-21 | 2018-03-29 | Alnylam Pharmaceuticals, Inc | Myostatin irna compositions and methods of use thereof |
EP3521430A4 (en) * | 2016-09-29 | 2020-05-20 | National University Corporation Tokyo Medical and Dental University | DOUBLE-STRANDED NUCLEIC ACID COMPLEX WITH OVERHEAD |
WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
WO2018107096A1 (en) | 2016-12-08 | 2018-06-14 | University Of Utah Research Foundation | Staufen1 agents and associated methods |
US20200085758A1 (en) | 2016-12-16 | 2020-03-19 | The Brigham And Women's Hospital, Inc. | Co-delivery of nucleic acids for simultaneous suppression and expression of target genes |
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 |
WO2018146557A2 (en) * | 2017-02-10 | 2018-08-16 | Dong Ki Lee | Long double-stranded rna for rna interference |
US10934547B2 (en) * | 2017-02-20 | 2021-03-02 | Northwestern University | Use of trinucleotide repeat RNAs to treat cancer |
DE102017103383A1 (de) | 2017-02-20 | 2018-08-23 | aReNA-Bio GbR (vertretungsberechtigter Gesellschafter: Dr. Heribert Bohlen, 50733 Köln) | System und Verfahren zur Zelltyp-spezifischen Translation von RNA-Molekülen in Eukaryoten |
WO2018160538A1 (en) | 2017-02-28 | 2018-09-07 | Mersana Therapeutics, Inc. | Combination therapies of her2-targeted antibody-drug conjugates |
US11261441B2 (en) | 2017-03-29 | 2022-03-01 | Bluebird Bio, Inc. | Vectors and compositions for treating hemoglobinopathies |
EP3606465A4 (en) | 2017-04-07 | 2021-03-24 | Apellis Pharmaceuticals, Inc. | DOSING PLANS, ASSOCIATED COMPOSITIONS AND PROCEDURES |
CN110945128B (zh) | 2017-04-14 | 2023-11-03 | 代表亚利桑那大学的亚利桑那董事会 | 用于治疗肺纤维化的组合物和方法 |
US11324820B2 (en) | 2017-04-18 | 2022-05-10 | Alnylam Pharmaceuticals, Inc. | Methods for the treatment of subjects having a hepatitis b virus (HBV) infection |
US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
WO2018218135A1 (en) | 2017-05-25 | 2018-11-29 | The Children's Medical Center Corporation | Bcl11a guide delivery |
CN110945030A (zh) * | 2017-06-20 | 2020-03-31 | 丹娜法伯癌症研究院 | 使用april-taci相互作用的调节剂调节调控性t细胞、调控性b细胞和免疫响应的方法 |
JP7406793B2 (ja) | 2017-06-23 | 2023-12-28 | ユニバーシティー オブ マサチューセッツ | 2テイル自己デリバリー型siRNAおよび関連方法 |
MX2019014800A (es) | 2017-07-06 | 2020-02-10 | Arrowhead Pharmaceuticals Inc | Agentes de iarn para la inhibicion de la expresion de alfa-enac y metodos de uso. |
EP3651775A4 (en) | 2017-07-13 | 2021-04-07 | Alnylam Pharmaceuticals, Inc. | METHOD FOR INHIBITION OF HAO1 (HYDROXYIC ACID OXIDASE-1 (GLYCOLATE OXIDASE) GENE EXPRESSION |
US11104700B2 (en) | 2017-07-17 | 2021-08-31 | Oxford University Innovation Limited | Oligonucleotides |
US11110114B2 (en) | 2017-07-17 | 2021-09-07 | Oxford University Innovation Limited | Dinucleotides |
BR112020002413A2 (pt) | 2017-09-11 | 2020-07-28 | Arrowhead Pharmaceuticals, Inc. | agentes rnai e composições para inibir a expressão de apolipoproteína c-iii (apoc3) |
MA50267A (fr) | 2017-09-19 | 2020-07-29 | Alnylam Pharmaceuticals Inc | Compositions et méthodes de traitement de l'amylose médiée par la transthyrétine (ttr) |
WO2019068326A1 (en) | 2017-10-05 | 2019-04-11 | Université D'aix-Marseille | INHIBITORS OF LSD1 FOR THE TREATMENT AND PREVENTION OF CARDIOMYOPATHIES |
CN118185936A (zh) | 2017-10-20 | 2024-06-14 | 戴瑟纳制药公司 | 治疗乙型肝炎感染的方法 |
WO2019100053A1 (en) | 2017-11-20 | 2019-05-23 | University Of Georgia Research Foundation, Inc. | Compositions and methods for modulating hif-2α to improve muscle generation and repair |
WO2019104289A1 (en) | 2017-11-27 | 2019-05-31 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
AU2018375807A1 (en) | 2017-12-01 | 2020-05-07 | The Texas A&M University System | Angelman syndrome antisense treatment |
KR102443358B1 (ko) | 2017-12-06 | 2022-09-14 | 어비디티 바이오사이언시스 인크. | 근위축증 및 근긴장성 이영양증을 치료하는 조성물 및 방법 |
TW201929908A (zh) | 2017-12-21 | 2019-08-01 | 美商梅爾莎納醫療公司 | 吡咯并苯并二氮呯抗體共軛物 |
US11597932B2 (en) | 2017-12-21 | 2023-03-07 | Alnylam Pharmaceuticals, Inc. | Chirally-enriched double-stranded RNA agents |
US10960086B2 (en) | 2017-12-28 | 2021-03-30 | Augusta University Research Institute, Inc. | Aptamer compositions and methods of use thereof |
US11865081B2 (en) | 2017-12-29 | 2024-01-09 | Virogin Biotech Canada Ltd. | Oncolytic viral delivery of therapeutic polypeptides |
KR20200106513A (ko) | 2018-01-05 | 2020-09-14 | 다이서나 파마수이티컬, 인크. | 면역요법을 강화시키기 위하여 베타-카테닌 및 ido 발현의 감소 |
CA3086409A1 (en) | 2018-01-16 | 2019-07-25 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting aldh2 expression |
EP3749766A1 (en) | 2018-02-09 | 2020-12-16 | F.Hoffmann-La Roche Ag | Oligonucleotides for modulating tmem106b expression |
CN112424375A (zh) | 2018-05-07 | 2021-02-26 | 罗氏创新中心哥本哈根有限公司 | 用于寡核苷酸治疗剂的大规模平行发现方法 |
AU2019266548A1 (en) | 2018-05-10 | 2021-01-07 | Complement Therapeutics Limited | Methods for assessing macular degeneration |
AU2019275071B2 (en) | 2018-05-24 | 2022-12-15 | Sirnaomics, Inc. | Composition and methods of controllable co-coupling polypeptide nanoparticle delivery system for nucleic acid therapeutics |
WO2019241734A1 (en) * | 2018-06-14 | 2019-12-19 | University Of Utah Research Foundation | Staufen1 regulating agents and associated methods |
EA202190528A1 (ru) | 2018-08-13 | 2021-04-23 | Элнилэм Фармасьютикалз, Инк. | КОМПОЗИЦИИ АГЕНТОВ дцРНК ВИРУСА ГЕПАТИТА B (HBV) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
US20210205264A1 (en) | 2018-09-04 | 2021-07-08 | H. Lee Moffitt Cancer Center & Research Institute Inc. | Use of delta-tocotrienol for treating cancer |
US20210317479A1 (en) | 2018-09-06 | 2021-10-14 | The Broad Institute, Inc. | Nucleic acid assemblies for use in targeted delivery |
JP2022513400A (ja) | 2018-10-29 | 2022-02-07 | メルサナ セラピューティクス インコーポレイテッド | ペプチド含有リンカーを有するシステイン操作抗体-薬物コンジュゲート |
KR20210132661A (ko) | 2019-02-12 | 2021-11-04 | 다이서나 파마수이티컬, 인크. | Cyp27a1의 발현을 억제하기 위한 방법 및 조성물 |
CN113924365A (zh) | 2019-03-29 | 2022-01-11 | 迪克纳制药公司 | 用于治疗kras相关疾病或病症的组合物和方法 |
EP3947683A1 (en) | 2019-04-04 | 2022-02-09 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting gene expression in the central nervous system |
US11814464B2 (en) | 2019-04-29 | 2023-11-14 | Yale University | Poly(amine-co-ester) polymers and polyplexes with modified end groups and methods of use thereof |
EP3963072A1 (en) | 2019-05-03 | 2022-03-09 | Dicerna Pharmaceuticals, Inc. | Double-stranded nucleic acid inhibitor molecules with shortened sense strands |
US20200369759A1 (en) | 2019-05-23 | 2020-11-26 | Fibrogen, Inc. | Methods of treatment of muscular dystrophies |
CA3144333A1 (en) | 2019-06-26 | 2020-12-30 | Biorchestra Co., Ltd. | Micellar nanoparticles and uses thereof |
CN114502730A (zh) | 2019-08-09 | 2022-05-13 | 马萨诸塞大学 | 经化学修饰的靶向snp的寡核苷酸 |
EP4021496A1 (en) | 2019-08-30 | 2022-07-06 | Yale University | Compositions and methods for delivery of nucleic acids to cells |
KR20220061972A (ko) | 2019-09-10 | 2022-05-13 | 다이이찌 산쿄 가부시키가이샤 | 간장 송달용 GalNAc-올리고뉴클레오티드 콘주게이트 및 제조 방법 |
KR20220069103A (ko) | 2019-10-02 | 2022-05-26 | 다이서나 파마수이티컬, 인크. | 최소 플루오린 함량을 갖는 작은 간섭 rna의 화학적 변형 |
US11355185B2 (en) | 2019-11-26 | 2022-06-07 | Cypress Semiconductor Corporation | Silicon-oxide-nitride-oxide-silicon multi-level non-volatile memory device and methods of fabrication thereof |
JP2023509870A (ja) | 2019-12-24 | 2023-03-10 | エフ. ホフマン-ラ ロシュ アーゲー | Hbvの処置のためのhbvを標的とする治療用オリゴヌクレオチドとtlr7アゴニストとの医薬組合せ |
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 |
AU2021207901A1 (en) | 2020-01-14 | 2022-09-08 | Synthekine, Inc. | IL2 orthologs and methods of use |
WO2021150300A1 (en) | 2020-01-22 | 2021-07-29 | Massachusetts Institute Of Technology | Inducible tissue constructs and uses thereof |
WO2021173965A1 (en) | 2020-02-28 | 2021-09-02 | Massachusetts Institute Of Technology | Identification of variable influenza residues and uses thereof |
BR112022018667A2 (pt) | 2020-03-18 | 2022-11-29 | Dicerna Pharmaceuticals Inc | Composições e métodos para inibir a expressão de ang-ptl3 |
US11555190B2 (en) | 2020-03-19 | 2023-01-17 | Avidity Biosciences, Inc. | Compositions and methods of treating Facioscapulohumeral muscular dystrophy |
JP2023527638A (ja) | 2020-03-27 | 2023-06-30 | アビディティー バイオサイエンシーズ,インク. | 顔面肩甲上腕型筋ジストロフィーを処置するための組成物および方法 |
BR112022021020A2 (pt) | 2020-04-22 | 2023-02-14 | Iovance Biotherapeutics Inc | Método de fabricação de um produto de terapia celular, métodos de tratamento do paciente com o produto de terapia celular de expansão e fabricado, e, método de fabricação de um produto de terapia celular |
WO2021255262A1 (en) | 2020-06-19 | 2021-12-23 | Sylentis Sau | siRNA AND COMPOSITIONS FOR PROPHYLACTIC AND THERAPEUTIC TREATMENT OF VIRUS DISEASES |
MX2022016581A (es) | 2020-06-19 | 2023-02-01 | Univ Yale | Polimeros de poli(amina-co-ester) con grupos de extremo modificado y liberacion pulmonar mejorada. |
US20220031633A1 (en) | 2020-07-28 | 2022-02-03 | Yale University | Poly(amine-co-ester) polymeric particles for selective pulmonary delivery |
EP4192478A2 (en) | 2020-08-04 | 2023-06-14 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting plp1 expression |
EP4192505A1 (en) | 2020-08-04 | 2023-06-14 | Dicerna Pharmaceuticals, Inc. | Systemic delivery of oligonucleotides |
TW202221120A (zh) | 2020-08-04 | 2022-06-01 | 美商黛瑟納製藥公司 | 用於治療代謝症候群之組成物及方法 |
EP4192954A1 (en) | 2020-08-05 | 2023-06-14 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting lpa expression |
KR20230043877A (ko) | 2020-08-05 | 2023-03-31 | 에프. 호프만-라 로슈 아게 | B형 간염 환자의 올리고뉴클레오티드 치료 |
MX2023002480A (es) | 2020-08-31 | 2023-05-18 | Univ Yale | "composiciones y métodos para el suministro de ácidos nucleicos a las células. |
EP3964204A1 (en) | 2020-09-08 | 2022-03-09 | Université d'Aix-Marseille | Lsd1 inhibitors for use in the treatment and prevention of fibrosis of tissues |
WO2022058447A1 (en) | 2020-09-16 | 2022-03-24 | The University Of Manchester | Complementome assay |
WO2022115645A1 (en) | 2020-11-25 | 2022-06-02 | Akagera Medicines, Inc. | Lipid nanoparticles for delivery of nucleic acids, and related methods of use |
CN117295753A (zh) | 2020-12-04 | 2023-12-26 | 基那奥生物公司 | 用于将核酸递送到细胞的组合物和方法 |
EP4015634A1 (en) | 2020-12-15 | 2022-06-22 | Sylentis, S.A.U. | Sirna and compositions for prophylactic and therapeutic treatment of virus diseases |
BR112023017737A2 (pt) | 2021-03-04 | 2023-10-03 | Alnylam Pharmaceuticals Inc | Composições de irna de angiopoietina-semelhantes 3 (angptl3) e métodos de uso das mesmas |
WO2022211740A1 (en) | 2021-03-31 | 2022-10-06 | Carmine Therapeutics Pte. Ltd. | Extracellular vesicles loaded with at least two different nucleic acids |
BR112023017367A2 (pt) | 2021-04-12 | 2023-12-12 | Boehringer Ingelheim Int | Composições e métodos para inibição de ceto-hexoquinase (khk) |
CA3209418A1 (en) | 2021-04-14 | 2022-10-20 | Utsav SAXENA | Compositions and methods for modulating pnpla3 expression |
MX2023012086A (es) | 2021-04-19 | 2023-10-25 | Novo Nordisk As | Composiciones y metodos para inhibir la expresion del miembro 3 del grupo h de la subfamilia 1 de receptores nucleares (nr1h3). |
EP4347820A1 (en) | 2021-05-28 | 2024-04-10 | Novo Nordisk A/S | Compositions and methods for inhibiting mitochondria amidoxime reducing component 1 (marc1) expression |
US20240254490A1 (en) | 2021-05-29 | 2024-08-01 | 1Globe Health Institute Llc | Short Duplex DNA as a Novel Gene Silencing Technology and Use Thereof |
EP4347829A1 (en) | 2021-05-29 | 2024-04-10 | 1Globe Health Institute LLC | Asymmetric short duplex dna as a novel gene silencing technology and use thereof |
MX2023015523A (es) | 2021-06-23 | 2024-03-11 | Univ Massachusetts | Compuestos de oligonucleotidos anti-flt1 optimizados para el tratamiento de la preeclampsia y otros desordenes angiogenicos. |
TW202328445A (zh) | 2021-08-03 | 2023-07-16 | 美商艾拉倫製藥股份有限公司 | 甲狀腺素運載蛋白(TTR)iRNA組成物及其使用方法 |
EP4388094A1 (en) | 2021-08-16 | 2024-06-26 | Vib Vzw | Oligonucleotides for modulating synaptogyrin-3 expression |
EP4392556A1 (en) | 2021-08-25 | 2024-07-03 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting ?lpha-1 antitrypsin expression |
AU2022349065A1 (en) | 2021-09-21 | 2024-04-04 | The Johns Hopkins University | Dendrimer conjugates of small molecule biologics for intracellular delivery |
AU2022384619A1 (en) | 2021-11-11 | 2024-04-11 | F. Hoffmann-La Roche Ag | Pharmaceutical combinations for treatment of hbv |
US20240043846A1 (en) | 2021-11-19 | 2024-02-08 | Kist (Korea Institute Of Science And Technology) | Therapeutic Compounds for Red Blood Cell-Mediated Delivery of an Active Pharmaceutical Ingredient to a Target Cell |
KR20240111757A (ko) | 2021-12-01 | 2024-07-17 | 다이서나 파마수이티컬, 인크. | Apoc3 발현을 조절하기 위한 조성물 및 방법 |
WO2023118546A2 (en) | 2021-12-23 | 2023-06-29 | Boehringer Ingelheim International Gmbh | METHODS AND MOLECULES FOR RNA INTERFERENCE (RNAi) |
WO2023159189A1 (en) | 2022-02-18 | 2023-08-24 | Yale University | Branched poly(amine-co-ester) polymers for more efficient nucleic expression |
GB202203627D0 (en) | 2022-03-16 | 2022-04-27 | Univ Manchester | Agents for treating complement-related disorders |
US20230302423A1 (en) | 2022-03-28 | 2023-09-28 | Massachusetts Institute Of Technology | Rna scaffolded wireframe origami and methods thereof |
GB202204884D0 (en) | 2022-04-04 | 2022-05-18 | Fondo Ricerca Medica S R I | Sirna targeting kcna1 |
WO2023201369A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | Til expansion processes using specific cytokine combinations and/or akti treatment |
AR129073A1 (es) | 2022-04-15 | 2024-07-10 | Dicerna Pharmaceuticals Inc | Composiciones y métodos para modular la actividad de scap |
US20230416742A1 (en) | 2022-05-12 | 2023-12-28 | Dicerna Phrmaceuticals, Inc. | Compositions and methods for inhibiting mapt expression |
WO2023220351A1 (en) | 2022-05-13 | 2023-11-16 | Dicerna Pharmaceuticals, Inc. | Compositions and methods for inhibiting snca expression |
WO2023230587A2 (en) | 2022-05-25 | 2023-11-30 | Akagera Medicines, Inc. | Lipid nanoparticles for delivery of nucleic acids and methods of use thereof |
TW202400193A (zh) | 2022-06-24 | 2024-01-01 | 丹麥商諾佛 儂迪克股份有限公司 | 抑制跨膜絲胺酸蛋白酶6(tmprss6)表現的組成物及方法 |
WO2024040041A1 (en) | 2022-08-15 | 2024-02-22 | Dicerna Pharmaceuticals, Inc. | Regulation of activity of rnai molecules |
WO2024081736A2 (en) | 2022-10-11 | 2024-04-18 | Yale University | Compositions and methods of using cell-penetrating antibodies |
WO2024107993A1 (en) | 2022-11-16 | 2024-05-23 | Dicerna Pharmaceuticals, Inc. | Stat3 targeting oligonucleotides and uses thereof |
WO2024108217A1 (en) | 2022-11-18 | 2024-05-23 | Genkardia Inc. | Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction |
WO2024112571A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
GB202219829D0 (en) | 2022-12-29 | 2023-02-15 | Ivy Farm Tech Limited | Genetically manipulated cells |
WO2024151877A2 (en) | 2023-01-11 | 2024-07-18 | Engage Biologics Inc. | Non-viral expression systems and methods of use thereof |
Family Cites Families (136)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2003006A (en) * | 1933-04-11 | 1935-05-28 | Michelson Barnett Samuel | Water tank cover |
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 |
US5208149A (en) * | 1983-10-20 | 1993-05-04 | The Research Foundation Of State University Of New York | Nucleic acid constructs containing stable stem and loop structures |
GB8704365D0 (en) * | 1987-02-25 | 1987-04-01 | Exxon Chemical Patents Inc | Zeolite l preparation |
IE66830B1 (en) | 1987-08-12 | 1996-02-07 | Hem Res Inc | Topically active compositions of double-stranded RNAs |
US5712257A (en) * | 1987-08-12 | 1998-01-27 | Hem Research, Inc. | Topically active compositions of mismatched dsRNAs |
US5703055A (en) * | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
DE69033495T2 (de) * | 1989-10-24 | 2000-07-20 | Isis Pharmaceuticals, Inc. | 2'-modifizierte nukleotide |
US5457189A (en) * | 1989-12-04 | 1995-10-10 | Isis Pharmaceuticals | Antisense oligonucleotide inhibition of papillomavirus |
US5670633A (en) * | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
DE69133405T2 (de) | 1990-01-11 | 2005-07-07 | Isis Pharmaceutical, Inc., Carlsbad | Oligonukleotidderivate zur detektieren und modulation von rna aktivität und genexpression |
US5514577A (en) * | 1990-02-26 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide therapies for modulating the effects of herpes viruses |
DE69123979T2 (de) * | 1990-10-12 | 1997-04-30 | Max Planck Gesellschaft | Abgeänderte ribozyme |
FR2675803B1 (fr) | 1991-04-25 | 1996-09-06 | Genset Sa | Oligonucleotides fermes, antisens et sens et leurs applications. |
WO1994008003A1 (en) * | 1991-06-14 | 1994-04-14 | Isis Pharmaceuticals, Inc. | ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE |
FR2685346B1 (fr) * | 1991-12-18 | 1994-02-11 | Cis Bio International | Procede de preparation d'arn double-brin, et ses applications. |
CA2131311C (en) * | 1992-03-05 | 2004-06-29 | Phillip Dan Cook | Covalently cross-linked oligonucleotides |
US5792751A (en) * | 1992-04-13 | 1998-08-11 | Baylor College Of Medicine | Tranformation of cells associated with fluid spaces |
US20030171311A1 (en) * | 1998-04-27 | 2003-09-11 | Lawrence Blatt | Enzymatic nucleic acid treatment of diseases or conditions related to hepatitis C virus infection |
US20030068301A1 (en) * | 1992-05-14 | 2003-04-10 | Kenneth Draper | Method and reagent for inhibiting hepatitis B virus replication |
US20030206887A1 (en) * | 1992-05-14 | 2003-11-06 | David Morrissey | RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) |
US20040054156A1 (en) * | 1992-05-14 | 2004-03-18 | Kenneth Draper | Method and reagent for inhibiting hepatitis B viral replication |
US5693535A (en) * | 1992-05-14 | 1997-12-02 | Ribozyme Pharmaceuticals, Inc. | HIV targeted ribozymes |
AU4770093A (en) | 1992-07-02 | 1994-01-31 | Hybridon, Inc. | Self-stabilized oligonucleotides as therapeutic agents |
US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
WO1994015645A1 (en) | 1992-12-31 | 1994-07-21 | Texas Biotechnology Corporation | Antisense molecules directed against genes of the raf oncogene family |
US6056704A (en) * | 1993-03-03 | 2000-05-02 | Ide; Masatake | Foot-pressure massage stand |
EP0616026A1 (en) | 1993-03-19 | 1994-09-21 | The Procter & Gamble Company | Concentrated cleaning compositions |
CA2165821C (en) * | 1993-06-23 | 2002-01-08 | Albert D. Friesen | Antisense oligonucleotides and therapeutic use thereof in human immunodeficiency virus infection |
FR2710074B1 (fr) | 1993-09-15 | 1995-12-08 | Rhone Poulenc Rorer Sa | Gène GRB3-3, ses variants et leurs utilisations. |
US5624803A (en) * | 1993-10-14 | 1997-04-29 | The Regents Of The University Of California | In vivo oligonucleotide generator, and methods of testing the binding affinity of triplex forming oligonucleotides derived therefrom |
US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
AU689182B2 (en) | 1993-11-16 | 1998-03-26 | Genta Incorporated | Chimeric oligonucleoside compounds |
US5578716A (en) * | 1993-12-01 | 1996-11-26 | Mcgill University | DNA methyltransferase antisense oligonucleotides |
US5908779A (en) * | 1993-12-01 | 1999-06-01 | University Of Connecticut | Targeted RNA degradation using nuclear antisense RNA |
EP0759979A4 (en) * | 1994-05-10 | 1999-10-20 | Gen Hospital Corp | ANTISENSE OLIGONUCLEOTIDES INHIBITION OF HEPATITIS C VIRUS |
US6057153A (en) * | 1995-01-13 | 2000-05-02 | Yale University | Stabilized external guide sequences |
US5674683A (en) * | 1995-03-21 | 1997-10-07 | Research Corporation Technologies, Inc. | Stem-loop and circular oligonucleotides and method of using |
US5624808A (en) * | 1995-03-28 | 1997-04-29 | Becton Dickinson And Company | Method for identifying cells committed to apoptosis by determining cellular phosphotyrosine content |
EP1489184A1 (en) | 1995-06-07 | 2004-12-22 | Inex Pharmaceutical Corp. | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
WO1997011170A1 (en) * | 1995-09-20 | 1997-03-27 | Worcester Foundation For Biomedical Research | Antisense oligonucleotide chemotherapy for benign hyperplasia or cancer of the prostate |
US5998203A (en) * | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
WO1997030067A1 (en) | 1996-02-14 | 1997-08-21 | Isis Pharmaceuticals, Inc. | Sugar-modified gapped oligonucleotides |
BR9708701A (pt) | 1996-04-17 | 2000-01-04 | Hoechst Marion Roussel De Gmbh | Inibidores anti-sense de expressão do fator de crescimento endotelial vascular. |
DE19618797C2 (de) | 1996-05-10 | 2000-03-23 | Bertling Wolf | Vehikel zum Transport molekularer Substanz |
US5898031A (en) * | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
US20040266706A1 (en) | 2002-11-05 | 2004-12-30 | Muthiah Manoharan | Cross-linked oligomeric compounds and their use in gene modulation |
DE19631919C2 (de) | 1996-08-07 | 1998-07-16 | Deutsches Krebsforsch | Anti-Sinn-RNA mit Sekundärstruktur |
US6225290B1 (en) * | 1996-09-19 | 2001-05-01 | The Regents Of The University Of California | Systemic gene therapy by intestinal cell transformation |
JP2002513276A (ja) * | 1996-10-04 | 2002-05-08 | デレク ナイジェル ジョン ハート | S―アデノシル―l―ホモシステイン加水分解酵素(ahcy)型活性を有する酵素 |
US5814500A (en) * | 1996-10-31 | 1998-09-29 | The Johns Hopkins University School Of Medicine | Delivery construct for antisense nucleic acids and methods of use |
AU727611B2 (en) | 1996-12-12 | 2000-12-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Synthetic antisense oligodeoxynucleotides and pharmaceutical compositions containing them |
US20030064945A1 (en) * | 1997-01-31 | 2003-04-03 | Saghir Akhtar | Enzymatic nucleic acid treatment of diseases or conditions related to levels of epidermal growth factor receptors |
GB9703146D0 (en) * | 1997-02-14 | 1997-04-02 | Innes John Centre Innov Ltd | Methods and means for gene silencing in transgenic plants |
US6218142B1 (en) * | 1997-03-05 | 2001-04-17 | Michael Wassenegger | Nucleic acid molecules encoding polypeptides having the enzymatic activity of an RNA-directed RNA polymerase (RDRP) |
GB9710475D0 (en) | 1997-05-21 | 1997-07-16 | Zeneca Ltd | Gene silencing |
ATE293123T1 (de) | 1997-09-12 | 2005-04-15 | Exiqon As | Bi- und tri-zyklische - nukleosid, nukleotid und oligonukleotid-analoga |
WO1999014346A2 (en) | 1997-09-19 | 1999-03-25 | Sequitur, Inc. | SENSE mRNA THERAPY |
GB9720148D0 (en) | 1997-09-22 | 1997-11-26 | Innes John Centre Innov Ltd | Gene silencing materials and methods |
US6506559B1 (en) * | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
US6475726B1 (en) * | 1998-01-09 | 2002-11-05 | Cubist Pharmaceuticals, Inc. | Method for identifying validated target and assay combinations for drug development |
CN101818145A (zh) | 1998-03-20 | 2010-09-01 | 联邦科学和工业研究组织 | 控制基因表达 |
AUPP249298A0 (en) * | 1998-03-20 | 1998-04-23 | Ag-Gene Australia Limited | Synthetic genes and genetic constructs comprising same I |
JP5015373B2 (ja) | 1998-04-08 | 2012-08-29 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼイション | 改良表現型を得るための方法及び手段 |
US20040214330A1 (en) * | 1999-04-07 | 2004-10-28 | Waterhouse Peter Michael | Methods and means for obtaining modified phenotypes |
EP1071753A2 (en) | 1998-04-20 | 2001-01-31 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid molecules with novel chemical compositions capable of modulating gene expression |
AR020078A1 (es) | 1998-05-26 | 2002-04-10 | Syngenta Participations Ag | Metodo para alterar la expresion de un gen objetivo en una celula de planta |
GB9827152D0 (en) | 1998-07-03 | 1999-02-03 | Devgen Nv | Characterisation of gene function using double stranded rna inhibition |
EP1050583A4 (en) | 1998-11-24 | 2005-02-02 | Hisamitsu Pharmaceutical Co | INHIBITORS OF HIV INFECTIONS |
WO2000032619A1 (en) | 1998-11-30 | 2000-06-08 | Ribogene, Inc. | Methods and compositions for identification of inhibitors of ribosome assembly |
US6939712B1 (en) * | 1998-12-29 | 2005-09-06 | Impedagen, Llc | Muting gene activity using a transgenic nucleic acid |
EP1147204A1 (en) * | 1999-01-28 | 2001-10-24 | Medical College Of Georgia Research Institute, Inc. | Composition and method for in vivo and in vitro attenuation of gene expression using double stranded rna |
DE19956568A1 (de) * | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
IL145778A0 (en) | 1999-04-21 | 2002-07-25 | American Home Prod | Methods and compositions for inhibiting the function of polynucleotide sequences |
US20040002153A1 (en) * | 1999-07-21 | 2004-01-01 | Monia Brett P. | Modulation of PTEN expression via oligomeric compounds |
GB9925459D0 (en) * | 1999-10-27 | 1999-12-29 | Plant Bioscience Ltd | Gene silencing |
GB9927444D0 (en) | 1999-11-19 | 2000-01-19 | Cancer Res Campaign Tech | Inhibiting gene expression |
DE10160151A1 (de) | 2001-01-09 | 2003-06-26 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens |
US7829693B2 (en) * | 1999-11-24 | 2010-11-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of a target gene |
DE10100586C1 (de) * | 2001-01-09 | 2002-04-11 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines Ziegens |
RU2164944C1 (ru) * | 1999-12-09 | 2001-04-10 | Институт молекулярной биологии им. В.А. Энгельгардта РАН | Способ изменения генетических свойств организма |
US8202979B2 (en) * | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
WO2001068826A2 (en) | 2000-03-14 | 2001-09-20 | Syngenta Participations Ag | Protoporphyrinogen oxidase ('protox') genes |
IL151781A0 (en) * | 2000-03-16 | 2003-04-10 | Genetica Inc | Methods and compositions for rna interference |
US20030084471A1 (en) * | 2000-03-16 | 2003-05-01 | David Beach | Methods and compositions for RNA interference |
PT2360253E (pt) | 2000-03-30 | 2014-05-29 | Max Planck Ges Zur Förderung Der Wissenschaften E V | Métodos de produção de células ou organismos knockdown através de interferência por rna com mediadores de rna específicos de sequência e usos dos mesmos |
WO2001075164A2 (en) * | 2000-03-30 | 2001-10-11 | Whitehead Institute For Biomedical Research | Rna sequence-specific mediators of rna interference |
WO2001092513A1 (en) | 2000-05-30 | 2001-12-06 | Johnson & Johnson Research Pty Limited | METHODS FOR MEDIATING GENE SUPPRESION BY USING FACTORS THAT ENHANCE RNAi |
US7033801B2 (en) | 2000-12-08 | 2006-04-25 | Invitrogen Corporation | Compositions and methods for rapidly generating recombinant nucleic acid molecules |
WO2003103600A2 (en) | 2002-06-05 | 2003-12-18 | Invitrogen Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
DK2813582T3 (en) * | 2000-12-01 | 2017-07-31 | Max-Planck-Gesellschaft Zur Förderung Der Wss E V | Small RNA molecules that mediate RNA interference |
JP2004532616A (ja) * | 2000-12-28 | 2004-10-28 | ジョンソン・アンド・ジョンソン・リサーチ・ピー・ティー・ワイ・リミテッド | 二本鎖rna仲介遺伝子抑制 |
US7423142B2 (en) * | 2001-01-09 | 2008-09-09 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of anti-apoptotic genes |
WO2003035869A1 (de) | 2001-10-26 | 2003-05-01 | Ribopharma Ag | Verwendung einer doppelsträngigen ribonukleinsäure zur gezielten hemmung der expression eines vorgegebenen zielgens |
EP1229134A3 (en) * | 2001-01-31 | 2004-01-28 | Nucleonics, Inc | Use of post-transcriptional gene silencing for identifying nucleic acid sequences that modulate the function of a cell |
EP1383782A1 (en) * | 2001-03-26 | 2004-01-28 | Sirna Therpeutics, Inc. | Oligonucleotide mediated inhibition of hepatitis b virus and hepatitis c virus replication |
US20040019001A1 (en) * | 2002-02-20 | 2004-01-29 | Mcswiggen James A. | RNA interference mediated inhibition of protein typrosine phosphatase-1B (PTP-1B) gene expression using short interfering RNA |
US20040006035A1 (en) * | 2001-05-29 | 2004-01-08 | Dennis Macejak | Nucleic acid mediated disruption of HIV fusogenic peptide interactions |
EP1390472A4 (en) * | 2001-05-29 | 2004-11-17 | Sirna Therapeutics Inc | NUCLEIC ACID TREATMENT OF DISEASES OR SIDES RELATED TO RAS, HER2 AND HIV LEVELS |
DE50101770D1 (de) | 2001-06-01 | 2004-04-29 | Mobilkom Austria Ag & Co Kg Wi | Verfahren zur Bestimmung des Standortes einer Mobilstation in einem Mobilfunksystem |
US20030140362A1 (en) * | 2001-06-08 | 2003-07-24 | Dennis Macejak | In vivo models for screening inhibitors of hepatitis B virus |
CA2462144C (en) | 2001-09-28 | 2016-09-20 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Micro-rna molecules |
DE10163098B4 (de) | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
US20050119202A1 (en) * | 2001-10-26 | 2005-06-02 | Roland Kreutzer | Medicament to treat a fibrotic disease |
DE10230997A1 (de) * | 2001-10-26 | 2003-07-17 | Ribopharma Ag | Medikament zur Erhöhung der Wirksamkeit eines Rezeptor-vermittelt Apoptose in Tumorzellen auslösenden Arzneimittels |
US20040121348A1 (en) * | 2001-10-26 | 2004-06-24 | Ribopharma Ag | Compositions and methods for treating pancreatic cancer |
DE10154113A1 (de) | 2001-11-03 | 2003-05-15 | Opel Adam Ag | Frontstruktur eines Kraftfahrzeuges |
DE10202419A1 (de) * | 2002-01-22 | 2003-08-07 | Ribopharma Ag | Verfahren zur Hemmung der Expression eines durch eine Chromosomen-Aberration entstandenen Zielgens |
EP1572902B1 (en) | 2002-02-01 | 2014-06-11 | Life Technologies Corporation | HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES |
CA2476530A1 (en) * | 2002-02-14 | 2003-08-21 | City Of Hope | Methods for producing interfering rna molecules in mammalian cells and therapeutic uses for such molecules |
WO2003076592A2 (en) * | 2002-03-06 | 2003-09-18 | Rigel Pharmaceuticals, Inc. | Novel method for delivery and intracellular synthesis of sirna molecules |
AU2003224725A1 (en) * | 2002-03-20 | 2003-10-08 | Brigham And Women's Hospital, Inc. | Hiv therapeutic |
US20030180756A1 (en) * | 2002-03-21 | 2003-09-25 | Yang Shi | Compositions and methods for suppressing eukaryotic gene expression |
US20040053876A1 (en) * | 2002-03-26 | 2004-03-18 | The Regents Of The University Of Michigan | siRNAs and uses therof |
AU2003237686A1 (en) | 2002-05-24 | 2003-12-12 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna interference mediating small rna molecules |
AU2003276666A1 (en) | 2002-06-12 | 2003-12-31 | Ambion, Inc. | Methods and compositions relating to polypeptides with rnase iii domains that mediate rna interference |
AU2003254334A1 (en) | 2002-07-10 | 2004-02-02 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Rna-interference by single-stranded rna molecules |
DK1527176T4 (en) | 2002-08-05 | 2017-07-03 | Silence Therapeutics Gmbh | ADDITIONAL NEW FORMS OF INTERFERRING RNA MOLECULES |
US20040241854A1 (en) * | 2002-08-05 | 2004-12-02 | Davidson Beverly L. | siRNA-mediated gene silencing |
US8729036B2 (en) * | 2002-08-07 | 2014-05-20 | University Of Massachusetts | Compositions for RNA interference and methods of use thereof |
EP1546344A4 (en) | 2002-09-18 | 2007-10-03 | Isis Pharmaceuticals Inc | EFFICIENT REDUCTION OF TARGET RNA USING OLIGOMERIC COMPOUNDS WITH SINGLE AND DOUBLE STRAPS |
EP1556402B1 (en) | 2002-09-25 | 2011-06-22 | University of Massachusetts | In vivo gene silencing by chemically modified and stable sirna |
EP1578765A4 (en) | 2002-11-05 | 2008-04-23 | Isis Pharmaceuticals Inc | OLIGOMERIC COMPOUNDS CONTAINING SUGAR SUBSTITUTE AND COMPOSITIONS FOR USE IN GENE MODULATION |
US8090542B2 (en) | 2002-11-14 | 2012-01-03 | Dharmacon Inc. | Functional and hyperfunctional siRNA |
AU2003295539A1 (en) | 2002-11-15 | 2004-06-15 | University Of Massachusetts | Allele-targeted rna interference |
AU2003298718A1 (en) * | 2002-11-22 | 2004-06-18 | University Of Massachusetts | Modulation of hiv replication by rna interference |
US20040224328A1 (en) * | 2003-01-15 | 2004-11-11 | Hans Prydz | siRNA screening method |
WO2004063375A1 (en) | 2003-01-15 | 2004-07-29 | Hans Prydz | OPTIMIZING siRNA BY RNAi ANTISENSE |
EP2333063A1 (en) | 2003-01-17 | 2011-06-15 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inducible small interfering RNA (sirna) expression constructs for targeted gene silencing |
WO2004065600A2 (en) | 2003-01-17 | 2004-08-05 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Rna interference by palindromic or modified rna molecules |
US20060247193A1 (en) | 2003-02-10 | 2006-11-02 | National Institute Of Advanced Industrial Science And Technology | Regulation of gene expression by dna interference |
NZ541967A (en) * | 2003-02-19 | 2008-07-31 | Commw Scient Ind Res Org | Gene silencing by double-stranded RNA in plants using a type 3 Pol III promoter |
AU2004248136B2 (en) | 2003-06-02 | 2011-09-15 | University Of Massachusetts | Methods and compositions for controlling efficacy of RNA silencing |
US6998203B2 (en) * | 2003-08-01 | 2006-02-14 | Intel Corporation | Proximity correcting lithography mask blanks |
ATE551421T1 (de) * | 2005-01-07 | 2012-04-15 | Alnylam Pharmaceuticals Inc | Rnai modulation von rsv und deren therapeutische verwendungen |
WO2013009634A2 (en) | 2011-07-08 | 2013-01-17 | Inteva Products Llc. | Method for stitching vehicle interior components and components formed from the method |
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