JP2019512489A - マイクロrnaおよびその使用方法 - Google Patents
マイクロrnaおよびその使用方法 Download PDFInfo
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Abstract
Description
本開示は、がんの処置および/または診断、特に、マイクロRNAを利用する方法に関する。
マイクロRNA(miR)発現の脱制御は、がんの複雑な悪性表現型を媒介する異常に発現したmRNAの潜在的に重要な寄与駆動因子として明らかになった(Stahlhut and Slack, Genome Med. 5:111, 2013)。どのmiRが、悪性表現型を調整する多様な経路および遺伝子プログラム内の極めて重要なmRNA標的を共制御するかは、それほど明らかではない。単一のmiRが複数のmRNAを同時に標的とし得るので、miRベースの治療剤は、がんにおいて単一のがん遺伝子または経路を標的とするより選択的な低分子または生物学的治療を使用して観察される固有のまたは獲得した抵抗性を緩和するのに役立ち得る。
がんにおいて増加または減少した発現を有するmiRNAが本明細書で開示される。開示されるmiRNAまたはそのミミックおよび/もしくはミメティックは、がん(例えば、悪性腫瘍)を有する被験体を処置および/または診断するための方法において利用され得る。
本明細書で列挙されるかまたは添付の配列表中の任意の核酸配列およびアミノ酸配列は、特許法施行規則§1.822に定義されるように、ヌクレオチド塩基およびアミノ酸に関する標準文字略語を使用して示される。少なくともいくらかの場合には、各核酸配列の一方の鎖のみが示されるが、相補鎖は、示された鎖への任意の言及によって包含されると理解される。
ゲノムワイド発現プロファイリング研究は、原発性腫瘍および細胞株においてmRNAおよびmiR発現の広い脱制御および不均一性(heterogeneity)を示した。これは、数百もの候補の中から、悪性表現型および治療抵抗性において決定的に重要なmiRおよびmRNAを同定するにあたって複雑性および難題を強調する。しかし、The Cancer Genome Atlas(TCGA)からの頭頚部および全がん分析の近年の発表(Cancer Genome Atlas Network Nature 517:576−582, 2015; Hoadleyら, Cell 158:929−944, 2014)まで、複数のプラットフォームからの包括的データは、最も顕著に変化したmiR、逆に発現されるmRNA、およびそれらの発現を駆動するゲノム変化の寄与を比較し同定するために、このような大きなデータセットから利用可能ではなかった。
CNV コピー数多型
HNSCC 頭頚部扁平上皮癌
miRNAまたはmiR マイクロRNA
RPM 100万個の塩基対あたりのリード数
RSEM 期待値最大化法によるRNA−Seq
SCC 扁平上皮癌
TCGA がんゲノムアトラス(The Cancer Genome Atlas)
XTT 3’−[1−(フェニルアミノカルボニル)−3,4−テトラゾリウム]−ビス(4−メトキシ−6−ニトロ)ベンゼンスルホン酸ナトリウム水和物
別段注記されなければ、技術用語は、従来からの使用法に従って使用される。分子生物学における一般的用語の定義は、以下において見出され得る:Benjamin Lewin, Genes VII, 出版:Oxford University Press, 2000 (ISBN 019879276X); Kendrewら(編), The Encyclopedia of Molecular Biology, 出版:Blackwell Publishers, 1994(ISBN 0632021829);およびRobert A. Meyers(編), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, 出版:Wiley, John & Sons, Inc., 1995 (ISBN 0471186341);ならびに他の類似の参考文献。
本明細書で開示されるのは、がん(扁平上皮腫瘍(squamous cell tumor)が挙げられるが、これらに限定されない)において差次的に制御されるmiRNAである。これらのmiRNAは、腫瘍を処置するための方法において利用され得、診断方法においても使用され得る。組成物および処置方法においても利用され得る改変miRNAがまた、開示される。
腫瘍において差次的に発現されるmiRNAが本明細書で開示される。これらmiRNAは、被験体においてがんを処置または阻害する方法において利用され得る。従って、本明細書で開示されるのは、有効量の1種またはこれより多くのmiRNAを被験体に投与することを包含する、該被験体においてがんを処置または阻害するための方法である。特定の例では、上記方法は、がんを有する被験体に、腫瘍においてダウンレギュレートされる1種またはこれより多くのmiRNAを、腫瘍(例えば、扁平上皮癌)を有する被験体に投与することを包含する。
本明細書で開示されるのは、被験体における腫瘍を診断するための方法である。いくつかの例では、上記方法は、例えば、コントロールと比較して、被験体に由来するサンプル中の1種またはこれより多くのmiRNAの量の変化(例えば、増加または減少)を検出することによって、被験体における腫瘍を同定することを包含する。いくつかの例では、上記方法は、腫瘍を有すると診断された被験体に処置を投与することをさらに包含する。一例において、上記被験体は、1種またはこれより多くのmiRNAの減少した量(例えば、コントロールと比較した場合)を発現する腫瘍を有すると診断され、有効量の、低下した発現を有する上記1種またはこれより多くのmiRNAを含む組成物が上記被験体に投与される。
材料および方法
HNSCC患者サンプル: 新鮮な凍結HNSCC組織および粘膜サンプルを、IRB承認プロトコルの一部としてUniversity of Michigan Medical Centerから集めた。そのHNSCC患者の臨床的特徴づけを、表2にまとめる。その集めた組織を急速凍結し、OCT凍結媒体(Fisher)にマウントし、7マイクロメートル切片に切り出し、H&E標準法によって染色した。その染色したスライドを、SCANSCOPE画像獲得デバイス(Aperio)を使用してスキャンし、IMAGESCOPEソフトウェア(Aperio)で調べて、腫瘍または粘膜扁平上皮の存在を担保した。その染色したスライドを使用して、組織ブロックを大きく切り出して(macrodissect)、各サンプルにおいて所望の扁平上皮腫瘍または上皮細胞の最低70%を達成した。
HNSCC組織におけるmiR−30ファミリーメンバーの減少した発現
HNSCC組織において差次的に発現されるmiRNA(miRs)を調べるために、279のHNSCCとTCGA(Cancer Genome Atlas 2015)によって公開された16の粘膜扁平上皮コントロール標本のmiR配列決定データを、分析した。腫瘍標本と粘膜標本との間の差次的発現分析を介して、129のmiR(77の増加したmiRおよび53の減少したmiRを含む(FDR<0.2;表3、図1;図2Aおよび2B))を同定した。これらの観察を、口腔由来の13のHNSCC標本およびUniversity of Michiganからの9個のマッチした粘膜サンプルの独立したパネルのmiR配列決定および発現分析によって検証した(表4)。両方のデータセットにおいて有意に変化しかつ検証されたmiRのペアワイズ比較は、miR−30ファミリーのいくつかのメンバーおよび以前の研究において同定されたいくつかのmiRの減少した発現を明らかにした(図2Cおよび図2D;表3および表4)。顕著なことには、miR−30−5pファミリーメンバーは、両方のコホートにおいて標本のうちの>70%にわたって少なくとも2倍の発現の減少を示した。
miR−30ファミリーメンバーは、HNSCC増殖を阻害する
miRNAの逆に発現された標的および成長促進シグナル伝達および転移性mRNAの相関
標的遺伝子発現のmiR−30a−5p直接的制御の機能的検証
miR−30−5pファミリーメンバーによる選択された標的遺伝子の直接的制御をさらに検証するために、EGFR、MET、IGF1RおよびIRS−1の3’ UTRを含むルシフェラーゼ構築物(これは、miR−30a−5pに対する標的結合部位を含む)を利用した(図6A)。miR−30a−5pのシード配列に相補的な結合部位に欠失を有するベクターも、構築した(図6A)。miR−30a−5p(しかし抗miR30aではない)は、レポーター活性を抑制し、これは、ΔmiR−30部位欠失によって排除された(図6B)。成長シグナル伝達(EGFR、MET、IGF1R、IRS1)、接着(ITGA6)および分化(FZD2)に関わるいくつかの分子の発現に対する効果をまた、ウェスタンブロットによって確認した(図6Cおよび6E)。これら成長因子レセプターは、いくつかの発がんシグナル伝達経路を刺激するので、PI3K/mTOR−AKT(Freudlspergerら, Expert Opin. Ther. Targets 15:63−74, 2011)、SRC(Egloffら, Semin. Oncol. 35:286−297, 2008)、およびSTAT3シグナル伝達(Mali, Oral Oncol. 51:565−569, 2015)へのシグナルリン酸化に対するmiR30a−5pの機能的効果を調べた。miR−30a−5pは、これらのシグナル伝達分子の下流のリン酸化を減少させた(図6D)。これらのデータは、HNSCCの悪性表現型において過剰発現され、これに関わる生物学的標的に対してmiR−30a−5pの直接的な制御効果を示す。
miR−30aは、HNSCC細胞による細胞増殖、運動性および侵入性を阻害する
複数のmiR−30a標的は、細胞成長をモジュレートし得るので、hsa−miR−30a−5pの抗増殖効果を、11種のHNSCC細胞株のパネルにおいて確認した。4種の細胞株(UM−SCC−11A、11B、46、47)は、コントロールと比較した場合、<50%の有意に減少した細胞密度を示し(図7A)、このことは、これらの細胞株におけるmiR−30a−5pの低い発現と一致した(図7B)。しかし、成長阻害はHOK細胞において観察されなかった。UM−SCC−1およびUM−SCC−46細胞におけるmiR−30a−5pおよびmiR−30e−5p発現の基底レベルを、qRT−PCRによって測定した(図7C)。増殖を、XTTアッセイによってUM−SCC−1またはUM−SCC−46細胞においても測定した。類似の増殖阻害が、ファミリーメンバー間で観察された(図7D)。
miR−30aミミックは、ヒトHNSCC異種移植片の腫瘍成長を抑制する
miR−30a−5pミミックを、送達のために、腫瘍細胞上に過剰発現されたトランスフェリンレセプターを標的とする、1本鎖抗体フラグメント(TfRscFv)を有するカチオン性リポソームナノ送達システム(scL)へと製剤化した(Pirolloら, Cancer Res. 68:1247−1250, 2008; Pirolloら, Hum. Gene Ther. 17:117−124, 2006)。FITC結合体化コントロールオリゴヌクレオチドを含むscLキャリアは、肺または肝臓と比較した場合に、HNSCC異種移植片において優先的な取り込みを受けるか、または腎臓を介して排出される(図9A)。改変miR−30a−5pミミックと複合体化したナノリポソーム粒子(miR−30a−scL)またはコントロールmiR(60μgまたは約3mg/kg)を、月曜日、水曜日、および金曜日(MWF)に3週間にわたって静脈内(IV)に9用量で与え、UM−SCC−46異種移植片腫瘍を担持するマウスにおいて試験した。有意な腫瘍成長遅延および生存の長期化が、miR−30a−scL処置で観察された(図9B〜D)。miR−30a−scLでの処置は、体重の有意な低下を引き起こさず、その処置が十分に許容されたことが示唆された(図9C)。インビボでの腫瘍成長に対する類似の阻害効果は、第2のHNSCC異種移植片モデル、UM−SCC47(これは、HPV陽性である)において観察された(図9E)。
HNSCCの臨床上の特徴と関連するmiR−30ファミリーメンバーの遺伝的変化
miR−30ファミリーメンバーの発現の喪失がHNSCCの病因において重要である場合、そこには、ゲノムレベルでの欠失または後生的なサイレンシングに対する選択圧があり得る。この疑問に対処するために、HNSCC TCGAデータセットからのmiR−30ファミリーメンバーのコピー数多型を分析した(図11Aおよび図11B)。MIR30AおよびMIR30C2遺伝子は、染色体6上で一緒にクラスター化され、MIR30EおよびMIR30C1遺伝子は、染色体1上で一緒にクラスター化され、ここでこれらの遺伝子座においてそれぞれ19.7%および14.7%が、少なくともヘテロ接合性喪失を示す。統合分析は、miR−30a(p=0.15、図11Aおよび図11C)およびmiR−30e(p=0.0006、図11Bおよび図11D)に関して、ヘテロ接合性コピー数喪失と発現の減少との傾向または有意な相関を裏付けた。本発明者らはさらに、観察されるmiR−30a/eのより広く減少した発現が、推定プロモーターのメチル化と関連するかどうかを分析し、平均DNAメチル化を、MIR30A/C2プロモーターおよびコード領域とともに比較した(表16)。MIR30AプロモーターのDNAメチル化の増加と、腫瘍標本のサブセットにおけるより低下した発現との間に、相関が観察された(p=0.00057、図11Cおよび図11F)。
がん細胞株におけるmiR−30aの抗増殖活性
がんのさらなるタイプの増殖に対するmiR−30aの効果を、ME180(子宮頸部扁平上皮癌)、HeLa(子宮頚部腺癌)、HCT116(結腸直腸癌)、DU−145(前立腺癌)、PC3(前立腺癌)、MDA−MB−231(乳房腺癌)、およびPanc1(膵臓癌)細胞株に対して試験した。細胞を、96ウェルプレートにおいて2×103 細胞/ウェルで播種し、15nM miR−30a二重鎖で48時間、0.15μlのRNAiMAXとともに逆トランスフェクトした。トランスフェクションの後に、培地を交換し、細胞を5日間インキュベートした。インキュベーションの後に、細胞生存性を、XTTアッセイによって測定した。miR−30aは、全ての試験した細胞株において細胞生存性を減少させた(図13)。
改変miR−30a miRNA
いくつかの改変された前駆体hsa−miR−30aミミックおよび/またはミメティックの設計および合成を行った。例示的な改変miR−30a核酸を、表18に示す。
細胞増殖に対する組み合わせmiRNA処置の効果
細胞生存性を、4種のmiRNA− M−miR30a−014、miR−145−5p、miR−26a−5p、およびmiR−375の混合物で、7.5nMまたは15nMの全二重鎖(それぞれ、各二重鎖が1.875nMまたは3.75nM)でトランスフェクトした9種のHNSCC腫瘍細胞株において評価した。他の実験では、7.5nMまたは15nMの全二重鎖においてmiRNAの対で細胞をトランスフェクトした。細胞を、96ウェルプレートにおいて1.5〜2×103細胞/ウェルで播種し、混合物で48時間、0.15μLのRNAiMAXとともに逆トランスフェクトした。一晩のトランスフェクションの後に、培地を交換し、細胞を4〜5日間インキュベートした。インキュベーション後、細胞生存性を、実施例1に記載されるようにXTTアッセイによって測定した。
細胞生存性に対するさらなるmiRNAの効果
細胞生存性を、miR27−5pまたはmiR−2b−1−5p二重鎖でトランスフェクトしたUM−SCC−1細胞またはUM−SCC−46細胞において評価した。96ウェルプレートにおいて、UM−SCC−1細胞を1.5×103細胞/ウェルで播種し、UM−SCC−46細胞を2×103細胞/ウェルで播種し、7.5nMまたは15nMの二重鎖で48時間、0.15μLのRNAiMAXとともに逆トランスフェクトした。トランスフェクションの後に、培地を交換し、細胞を5日間インキュベートした。細胞生存性をXTTアッセイによって測定した。
改変miRNA
いくつかのmiRミミックおよび/またはミメティックの設計を行った。例示的なmiRミミックおよび/またはミメティックを表20に示す。
頭頚部扁平上皮癌の処置
この実施例は、被験体においてHNSCCを処置または阻害するために使用され得る方法を記載する。しかし、当業者は、本明細書中の教示に基づいて、これらの具体的方法から外れた方法がまた、HNSCCを成功裡に処置するために使用され得ることを理解する。当業者はまた、これらの方法がまた、被験体において他のがんを処置または阻害するために使用され得ることを認識する。
さらなるmiR−30ミミックの設計および試験
さらなる改変miR−30−5pガイド鎖およびパッセンジャー鎖を設計した。これを表21に示す。
さらなるmiRミミック
Claims (35)
- がんを有する被験体を処置するための方法であって、該方法は、有効量の、miR−30核酸、miR−26a−5p核酸、miR−26b−5p核酸、miR−145−5p核酸、miR−338−3p核酸、miR−205−5p核酸、miR−375核酸、miR−29核酸、miR−27核酸、miR−101核酸、これらのうちのいずれかのミミックおよび/もしくはミメティック、またはこれらのうちのいずれか2種もしくはこれより多くの組み合わせを含む単離されたマイクロRNA(miRNA)核酸を該被験体に投与し、それによってがんを有する該被験体を処置することを包含する、方法。
- 前記miR−30核酸は、miR−30a−5p核酸、miR−30b−5p核酸、miR−30c−5p核酸、miR−30d−5p核酸、miR−30e−5p核酸、またはこれらのミミックおよび/もしくはミメティックである、請求項1に記載の方法。
- 前記miR−30核酸またはそのミミックおよび/もしくはミメティックは、配列番号42および配列番号56の二重鎖、配列番号42および配列番号57の二重鎖、または配列番号1〜11、配列番号37〜61、および配列番号66のうちの1つもしくはこれより多くを含む、請求項1または請求項2に記載の方法。
- 前記miR−30核酸またはそのミミックおよび/もしくはミメティックは、配列番号73〜92、配列番号50および配列番号61の二重鎖、配列番号73および配列番号61の二重鎖、または配列番号74および配列番号61の二重鎖のうちの1つもしくはこれより多くを含む、請求項1または請求項2に記載の方法。
- 前記miR−26a−5p核酸またはそのミミックおよび/もしくはミメティックは、配列番号12を含み、前記miR−26b−5p核酸またはそのミミックおよび/もしくはミメティックは、配列番号15を含み、前記miR−145−5p核酸またはそのミミックおよび/もしくはミメティックは、配列番号18を含み、前記miR−338−3p核酸またはそのミミックおよび/もしくはミメティックは、配列番号21を含み、前記miR−375核酸またはそのミミックおよび/もしくはミメティックは、配列番号17を含む、請求項1〜4のいずれか1項に記載の方法。
- 前記miR−26a−5pミミックまたはミメティックは、配列番号64、配列番号65、および配列番号105〜115のうちの1つまたはこれより多くを含み、前記miR−145−5pミミックまたはミメティックは、配列番号66、配列番号67、および配列番号116〜125のうちの1つまたはこれより多くを含み、前記miR−375ミミックまたはミメティックは、配列番号62、配列番号63、および配列番号93〜104のうちの1つまたはこれより多くを含み、前記miR−101ミミックまたはミメティックは、配列番号126〜135のうちの1つまたはこれより多くを含み、前記miR−29ミミックまたはミメティックは、配列番号136〜146のうちの1つまたはこれより多くを含み、または前記miR−27ミミックまたはミメティックは、配列番号147〜158のうちの1つまたはこれより多くを含む、請求項5に記載の方法。
- 前記方法は、有効量の、前記miR−30核酸、前記miR−26a−5p核酸、前記miR−145−5p核酸、ならびに前記miR−375核酸またはこれらのミミックおよび/もしくはミメティックを投与することを包含する、請求項1〜6のいずれかに記載の方法。
- 前記miRNA核酸および/またはそのミミックもしくはミメティックは、表6〜14に列挙される1つまたはこれより多くのmRNAの発現を減少させる、請求項1〜7のいずれか1項に記載の方法。
- 1種またはこれより多くの前記単離されたmiRNA核酸は、リポソーム組成物において投与される、請求項1〜8のいずれか1項に記載の方法。
- 前記リポソームは、該リポソームを前記がんに向かわせる1種またはこれより多くの分子をさらに含む、請求項9に記載の方法。
- 前記標的化分子は、抗トランスフェリンレセプター抗体またはそのフラグメントを含む、請求項10に記載の方法。
- 前記がんは、扁平上皮癌を含む、請求項1〜11のいずれか1項に記載の方法。
- 前記扁平上皮癌は、頭頚部の扁平上皮癌、肺の扁平上皮癌、または子宮頸部の扁平上皮癌を含む、請求項12に記載の方法。
- 前記がんは、上皮起源のがんであり、子宮頸部の腺癌、結腸直腸癌、前立腺癌、乳房腺癌、および膵臓癌の群から選択される、請求項1〜12のいずれか1項に記載の方法。
- 1種またはこれより多くのさらなる治療を投与することをさらに包含する、請求項1〜14のいずれか1項に記載の方法。
- 前記1種またはこれより多くのさらなる治療は、外科手術、放射線療法、および化学療法を含む、請求項15に記載の方法。
- 少なくとも1種のmiR−30ミミックもしくはミメティック核酸、少なくとも1種のmiR−375ミミックもしくはミメティック核酸、少なくとも1種のmiR−26a−5pミミックもしくはミメティック核酸、または少なくとも1種のmiR−145−5pミミックもしくはミメティック核酸を含む、組成物。
- 少なくとも1種のmiR−101ミミックもしくはミメティック核酸、少なくとも1種のmiR−29ミミックもしくはミメティック核酸、または少なくとも1種のmiR−27ミミックもしくはミメティック核酸を含む、組成物。
- 前記ミミックまたはミメティック核酸は、5’末端改変、および/または3’末端改変の、1種もしくはこれより多くの改変核酸を含む、請求項17または18に記載の組成物。
- 前記ミミックまたはミメティック核酸は、2’−O−メチル改変、2’−メトキシエトキシ改変、2’−ジメチルアミノオキシエトキシ改変、2’−アミノプロポキシ改変、および2’−フルオロ改変のヌクレオチドのうちの1種またはこれより多くを含む、請求項17〜19のいずれか1項に記載の組成物。
- 前記ミミックまたはミメティック核酸は、5’−アミノC3改変、5’−アミノC6改変、または5’−アミノC12改変を含む、請求項17〜20のいずれか1項に記載の組成物。
- 前記ミミックまたはミメティック核酸は、配列番号37〜67、配列番号42および配列番号56の二重鎖、または配列番号42および配列番号57の二重鎖のうちのいずれか1つを含む、請求項17〜21のいずれか1項に記載の組成物。
- 前記ミミックまたはミメティック核酸は、配列番号73〜125、配列番号50および配列番号61の二重鎖、配列番号73および配列番号61の二重鎖、または配列番号74および配列番号61の二重鎖のうちのいずれか1つを含む、請求項17または19〜21に記載の組成物。
- 前記ミミックまたはミメティック核酸は、配列番号126〜158のいずれか1つを含む、請求項18〜21のいずれか1項に記載の組成物。
- 前記ミミックまたはミメティック核酸は、ナノ粒子またはリポソームの中に組み込まれる、請求項17〜24のいずれか1項に記載の組成物。
- 前記リポソームは、前記ナノ粒子またはリポソームを腫瘍に向かわせる1種またはこれより多くの分子をさらに含む、請求項25に記載の組成物。
- 前記標的化分子は、抗トランスフェリンレセプター抗体またはそのフラグメントを含む、請求項26に記載の組成物。
- 薬学的に受容可能なキャリアをさらに含む、請求項27〜27のいずれか1項に記載の組成物。
- 固形腫瘍を有する被験体を処置するための方法であって、該方法は、有効量の、請求項17〜28のいずれか1項に記載の組成物を該被験体に投与することを包含する、方法。
- 腫瘍を有する被験体を診断するための方法であって、該方法は、
該被験体から得られたサンプル中で少なくとも1種のマイクロRNA(miRNA)核酸の発現を検出することであって、ここで該少なくとも1種のmiRNA核酸は、表1、表3、表4、表5、表18、および表20のうちのいずれか1つに列挙されるmiRNA核酸のうちの少なくとも1種を含む、こと;ならびに
該被験体から得られた該サンプル中での該miRNA核酸のうちの少なくとも1種の発現を、コントロールと比較すること、
を包含し、
ここで該コントロールと比較した該被験体から得られた該サンプル中の該miRNA核酸の変化した発現は、腫瘍を有する被験体を同定する、方法。 - 前記少なくとも1種のmiRNA核酸は、miR−30、miR−26a−5p、miR−26b−5p、miR−145−5p、miR−375、miR−338−3p、miR−375、miR−27、miR−29、またはmiR−101核酸を含む、請求項30に記載の方法。
- 前記少なくとも1種のmiRNA核酸は、miR−30、miR−26a−5p、miR−26b−5p、miR−145−5p、miR−375、およびmiR−338−3pの各々を含む、請求項31に記載の方法。
- 前記被験体は、扁平上皮癌の腫瘍を有する、請求項30〜32のいずれか1項に記載の方法。
- 前記被験体に由来する前記サンプルは、該被験体に由来する腫瘍サンプルである、請求項30〜33のいずれか1項に記載の方法。
- 前記miRNAの前記変化した発現が、前記コントロールと比較して減少した発現である場合に、表1、表3、表4、表5、表18、表20、表21、および表23のうちのいずれか1つに列挙されるmiRNA核酸のうちの少なくとも1種の有効量を前記被験体に投与することをさらに包含する、請求項30〜34のいずれか1項に記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
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EP3492607A3 (en) * | 2017-11-30 | 2019-08-14 | Università Degli Studi Di Torino | Urinary mirnas for the in vitro diagnosis of bladder cancer |
EP3965895A4 (en) * | 2019-05-08 | 2023-10-25 | Nova Southeastern University | REGULATION OF NUCLEOTIDE EXCISION REPAIR (NER) BY MICRORNA FOR THE TREATMENT OF BREAST CANCER |
CN111235274A (zh) * | 2020-01-18 | 2020-06-05 | 山西医科大学第一医院 | 喉鳞癌血清外泌体标志物筛选方法和外泌体来源miR-941应用 |
JP2023521042A (ja) * | 2020-04-02 | 2023-05-23 | ミレキュール インコーポレイテッド | 操作されたオリゴヌクレオチドを使用する標的化された阻害 |
CN112007043B (zh) * | 2020-08-24 | 2021-07-20 | 谢琦 | 抗结直肠癌的药物或组合物 |
WO2022056454A2 (en) * | 2020-09-14 | 2022-03-17 | President And Fellows Of Harvard College | Methods and compositions for treating hpv-positive cancers |
CN112294960B (zh) * | 2020-10-30 | 2022-02-08 | 浙江大学 | 微小分子RNA-30b-5p作为靶分子的用途 |
CN112359115B (zh) * | 2020-11-30 | 2022-08-30 | 河北仁博科技有限公司 | 与肿瘤细胞顺铂耐药性相关的miR-517a-3p及其应用 |
CN112481273B (zh) * | 2020-12-29 | 2023-11-24 | 南通大学附属医院 | 结直肠癌抑癌基因及其启动子区高dna甲基化的验证方法 |
EP4124656A1 (en) * | 2021-07-26 | 2023-02-01 | Martin-Luther-Universität Halle-Wittenberg | Pd-l1 micrornas |
CN113528669A (zh) * | 2021-08-19 | 2021-10-22 | 柳州市工人医院 | 一种利用Small RNA测序技术揭示miRNA对肝癌作用机制的方法 |
WO2023137528A1 (en) * | 2022-01-21 | 2023-07-27 | Griffith University | Biomarkers and uses therefor |
CN114574596B (zh) * | 2022-03-11 | 2023-06-23 | 浙江省农业科学院 | SNPs分子标记g.43851G>A及其在湖羊分子标记辅助育种中的应用 |
CN115161321B (zh) * | 2022-06-24 | 2023-04-18 | 天津市农业科学院 | ssc-miR-30c-3p在制备抗PDCoV增殖药物中的应用 |
WO2024015724A1 (en) * | 2022-07-10 | 2024-01-18 | Precigen, Inc. | POLYCISTRONIC miRNA CONSTRUCTS FOR IMMUNE CHECKPOINT INHIBITION |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005017145A1 (ja) * | 2003-08-13 | 2005-02-24 | Japan Biological Informatics Consortium | 機能性rnaが制御する被制御遺伝子の同定・予測方法及びその利用方法 |
JP2006248978A (ja) * | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
JP2009519339A (ja) * | 2005-12-12 | 2009-05-14 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 筋細胞増殖及び分化を調節するマイクロrna |
JP2010535246A (ja) * | 2007-07-31 | 2010-11-18 | ボード オブ リージェンツ, ザ ユニバーシティー オブ テキサス システム | ミオシンの発現及び筋線維の同一性を制御するマイクロrna |
JP2012529295A (ja) * | 2009-06-08 | 2012-11-22 | ミラゲン セラピューティクス | miRNA阻害剤およびミメティクスの化学修飾モチーフ |
JP2014506789A (ja) * | 2011-02-03 | 2014-03-20 | マーナ セラピューティクス インコーポレイテッド | miR−124の合成模倣体 |
JP2014506791A (ja) * | 2011-02-03 | 2014-03-20 | マーナ セラピューティクス インコーポレイテッド | miR−34の合成模倣体 |
JP2014530222A (ja) * | 2011-10-06 | 2014-11-17 | ミラゲン セラピューティクス, インコーポレイテッド | マイクロrnaの調節による全身エネルギーホメオスタシスの制御 |
US20150313932A1 (en) * | 2014-04-14 | 2015-11-05 | Dana-Farber Cancer Institute, Inc. | Composition and method for treating a hematological malignancy |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
PT1504126E (pt) | 2002-05-03 | 2014-06-02 | Univ Duke | Um método para regular a expressão génica |
WO2006078278A2 (en) | 2004-04-27 | 2006-07-27 | Alnylam Pharmaceuticals, Inc. | Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety |
US7674778B2 (en) | 2004-04-30 | 2010-03-09 | Alnylam Pharmaceuticals | Oligonucleotides comprising a conjugate group linked through a C5-modified pyrimidine |
JP2008504840A (ja) | 2004-06-30 | 2008-02-21 | 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 | 非リン酸骨格結合を含むオリゴヌクレオチド |
CA2574088C (en) | 2004-07-21 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
WO2006133022A2 (en) | 2005-06-03 | 2006-12-14 | The Johns Hopkins University | Compositions and methods for decreasing microrna expression for the treatment of neoplasia |
US20070213292A1 (en) | 2005-08-10 | 2007-09-13 | The Rockefeller University | Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof |
CN103028120B (zh) | 2005-09-12 | 2015-08-12 | 俄亥俄州立大学研究基金会 | 用于诊断或治疗bcl2相关癌症的组合物和方法 |
US8603991B2 (en) | 2005-11-18 | 2013-12-10 | Gradalis, Inc. | Individualized cancer therapy |
US8148069B2 (en) | 2006-01-05 | 2012-04-03 | The Ohio State University | MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of solid cancers |
WO2007143752A2 (en) | 2006-06-09 | 2007-12-13 | The Regents Of The University Of California | Targets in breast cancer for prognosis or therapy |
US20100292299A1 (en) | 2006-06-20 | 2010-11-18 | Mendell Joshua T | Nucleotide Motifs Providing Localization Elements and Methods of Use |
US8114982B2 (en) | 2006-12-06 | 2012-02-14 | Albert Einstein College Of Medicine Of Yeshiva University | Multi-microRNA methods and compositions |
WO2008073915A2 (en) | 2006-12-08 | 2008-06-19 | Asuragen, Inc. | Micrornas differentially expressed in leukemia and uses thereof |
JP2010516249A (ja) | 2007-01-17 | 2010-05-20 | ザ・ジョンズ・ホプキンス・ユニバーシティ | 腫瘍治療のためのミクロrnaに関する組成物及び方法 |
WO2009075817A1 (en) * | 2007-12-06 | 2009-06-18 | Minerva Biotechnologies Corporation | Method for treating cancer using interference rna |
EP2306978A2 (en) | 2008-06-06 | 2011-04-13 | Mirna Therapeutics, Inc. | Compositions for the in vivo delivery of rnai agents |
JP2010094122A (ja) | 2008-06-12 | 2010-04-30 | Keio Gijuku | バイオマーカーとしてのマイクロrnaを用いた頭頸部腫瘍の診断・治療選択 |
US8729041B2 (en) | 2008-12-03 | 2014-05-20 | The Johns Hopkins University | Compositions and methods for treating hepatic neoplasia |
WO2011034811A1 (en) | 2009-09-17 | 2011-03-24 | Sigma-Aldrich Co. | Short rna mimetics |
JP5935030B2 (ja) * | 2010-05-14 | 2016-06-15 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | 白血病を治療するための組成物および方法 |
TWI516267B (zh) | 2011-11-07 | 2016-01-11 | 臺北榮民總醫院 | 抑制癌症或腫瘤細胞之類癌幹細胞特性及抗化學及放射治療特性的醫藥組合物 |
KR102390629B1 (ko) * | 2014-04-25 | 2022-04-26 | 칠드런'즈 메디컬 센터 코포레이션 | 헤모글로빈병증을 치료하기 위한 조성물 및 방법 |
-
2017
- 2017-03-07 WO PCT/US2017/021178 patent/WO2017156015A2/en active Application Filing
- 2017-03-07 CN CN202410174426.2A patent/CN117757794A/zh active Pending
- 2017-03-07 EP EP17712348.6A patent/EP3426781A2/en active Pending
- 2017-03-07 CN CN201780027750.XA patent/CN109312341B/zh active Active
- 2017-03-07 JP JP2018547943A patent/JP2019512489A/ja active Pending
- 2017-03-07 US US16/082,852 patent/US11655469B2/en active Active
- 2017-03-07 CN CN202410174429.6A patent/CN117757795A/zh active Pending
-
2023
- 2023-04-14 US US18/301,040 patent/US20230295631A1/en active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005017145A1 (ja) * | 2003-08-13 | 2005-02-24 | Japan Biological Informatics Consortium | 機能性rnaが制御する被制御遺伝子の同定・予測方法及びその利用方法 |
JP2006248978A (ja) * | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
JP2009519339A (ja) * | 2005-12-12 | 2009-05-14 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 筋細胞増殖及び分化を調節するマイクロrna |
JP2010535246A (ja) * | 2007-07-31 | 2010-11-18 | ボード オブ リージェンツ, ザ ユニバーシティー オブ テキサス システム | ミオシンの発現及び筋線維の同一性を制御するマイクロrna |
JP2012529295A (ja) * | 2009-06-08 | 2012-11-22 | ミラゲン セラピューティクス | miRNA阻害剤およびミメティクスの化学修飾モチーフ |
JP2014506789A (ja) * | 2011-02-03 | 2014-03-20 | マーナ セラピューティクス インコーポレイテッド | miR−124の合成模倣体 |
JP2014506791A (ja) * | 2011-02-03 | 2014-03-20 | マーナ セラピューティクス インコーポレイテッド | miR−34の合成模倣体 |
JP2014530222A (ja) * | 2011-10-06 | 2014-11-17 | ミラゲン セラピューティクス, インコーポレイテッド | マイクロrnaの調節による全身エネルギーホメオスタシスの制御 |
US20150313932A1 (en) * | 2014-04-14 | 2015-11-05 | Dana-Farber Cancer Institute, Inc. | Composition and method for treating a hematological malignancy |
Non-Patent Citations (5)
Title |
---|
JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. Volume 135, Supplement 1, JPN6022007527, 2015, pages 99 - 105, ISSN: 0004866923 * |
MOL. BIOL. REP., vol. 41, JPN6021011285, 2014, pages 2779 - 2788, ISSN: 0004866920 * |
MOLECULAR AND CELLULAR BIOLOGY, vol. 35, no. 6, JPN6021011286, 2015, pages 988 - 1000, ISSN: 0004866921 * |
ONCOGENE, vol. 33, JPN6021011284, 2014, pages 3119 - 3128, ISSN: 0004866919 * |
日本癌学会学術総会抄録集(WEB), vol. 73, JPN6022007529, 2014, pages 1125, ISSN: 0004866922 * |
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