序号 专利名 申请号 申请日 公开(公告)号 公开(公告)日 发明人
1 改善心脏功能的基于细胞和基因的方法 CN201280034527.5 2012-05-29 CN103946230B 2017-02-08 M·雷尼尔; M·拉弗拉梅; C·默里; F·S·科尔特; S·伦迪; S·D·豪施卡; J·S·张伯伦; G·奥多姆
提供了用于改善哺乳动物的心脏功能、心肌收缩和舒张的组合物和方法。将用一个或多个表达载体转染的心肌细胞移植至哺乳动物心肌,所述表达载体包含有效地连接于启动子的核糖核苷酸还原酶亚基R1编码核酸序列和核糖核苷酸还原酶亚基R2编码核酸序列。还提供了用于通过移植过表达R1和R2的供体细胞而向心肌递送dATP的组合物和方法。由此原位产生dATP并通过在供体细胞和宿主心肌细胞之间形成的缝隙连接而递送。或者,将具有R1和R2编码构建体的病毒载体直接给哺乳动物施用。心脏功能的改善还可通过施用包含编码L48Q-Q、61Q或L57Q cTnC变体的核酸序列的载体来实现。
2 改善心脏功能的基于细胞和基因的方法 CN201280034527.5 2012-05-29 CN103946230A 2014-07-23 M·雷尼尔; M·拉弗拉梅; C·默里; F·S·科尔特; S·伦迪; S·D·豪施卡; J·S·张伯伦
发明提供了用于改善哺乳动物的心脏功能、心肌收缩和舒张的组合物和方法。将用一个或多个表达载体转染的心肌细胞移植至哺乳动物心肌,所述表达载体包含有效地连接于启动子的核糖核苷酸还原酶亚基R1编码核酸序列和核糖核苷酸还原酶亚基R2编码核酸序列。还提供了用于通过移植过表达R1和R2的供体细胞而向心肌递送dATP的组合物和方法。由此原位产生dATP并通过在供体细胞和宿主心肌细胞之间形成的缝隙连接而递送。或者,将具有R1和R2编码构建体的病毒载体直接给哺乳动物施用。心脏功能的改善还可通过施用包含编码L48Q-Q、61Q或L57Q cTnC变体的核酸序列的载体来实现。
3 利用核糖核苷酸还原酶R1抑制恶性肿瘤 CN98805031.5 1998-03-18 CN1256632A 2000-06-14 J·A·莱特; A·H·扬
发明提供通过使肿瘤细胞与生长调节量哺乳动物核糖核苷酸还原酶R1的可表达核酸序列相互作用来调节人或者其它哺乳动物中细胞恶性特征的方法。本发明还提供和应用生长调节量核糖核苷酸还原酶R1蛋白或生物学活性肽来调节人或其它哺乳动物中细胞恶性特性。可表达核酸序列可以用于基因治疗的载体形式存在。
4 Compositions and methods for inhibiting expression of RRM2 genes US15415415 2017-01-25 US09938531B2 2018-04-10 John Frederick Boylan; Birgit Bramlage; Markus Hossbach; John Reidhaar-Olson
The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.
5 Cell and gene based methods to improve cardiac function US14122226 2012-05-29 US09868937B2 2018-01-16 Michael Regnier; Michael Laflamme; Charles Murry; F. Steven Korte; Scott Lundy; Stephen Denison Hauschka; Jeffrey S. Chamberlain; Guy Odom
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
6 CELL AND GENE BASED METHODS TO IMPROVE CARDIAC FUNCTION US14122226 2012-05-29 US20160186139A1 2016-06-30 Michael Regnier; Michael Laflamme; Charles Murry; F. Steven Korte; Scott Lundy; Stephen Denison Hauschka; Jeffrey S. Chamberlain
Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.
7 Combination viral-based and gene-based therapy of tumors US09302952 1999-04-30 US06602499B1 2003-08-05 E. Antonio Chiocca; Xandra O. Breakefield
The present invention relates to viral mutants and methods of using these viral mutants for selectively killing neoplastic cells. The viral mutants of the invention are capable of selectively killing neoplastic cells by a combination of viral mediated oncolysis and anti-cancer (“suicide”) gene therapy.
8 SUPRESSION OF MALIGNANCY UTILIZING RIBONUCLEOTIDE REDUCTASE R1 US09155246 1998-09-24 US20020004488A1 2002-01-10 JIM A. WRIGHT; AIPING H. YOUNG
The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.
9 Methods of identifying compounds that inhibit DNA synthesis in mycobacterium tuberculosis and compositions, reagents and kits for performing the same US813940 1997-03-03 US5834279A 1998-11-10 Harvey Rubin; Fude Yang; David Avarbock; Sean Curran
Nucleic acid molecules that encode R2 subunit protein and topoisomerase I protein, fragments thereof, recombinant expression vectors and host cells are disclosed. Oligonucleotide molecules with nucleotide sequences complimentary to a nucleotide sequence encode R2 subunit protein and topoisomerase I protein are disclosed.
10 Cardiac function improvement methods based on cell and gene JP2014512189 2012-05-29 JP2014517694A 2014-07-24 レグニアー、マイケル; ラフラム、マイケル; マリー、チャールズ; コート、エフ.、スティーヴン; ランディー、スコット; ハウシュカ、ステファン、デニソン; チャンバーレイン、ジェフリー、エス.
哺乳動物における心臓機能、心筋収縮性及び弛緩を改善するための組成物及び方法を提供する。 プロモーターと操作可能に連結された、リボヌクレオチドレダクターゼサブユニットR1をコードする核酸配列及びリボヌクレオチドレダクターゼサブユニットR2をコードする核酸配列を含む1以上の発現ベクターでトランスフェクトされた心筋細胞を、哺乳動物心筋に移植する。 あるいは、R1及びR2をコードする構築物(1以上)を有するウイルウスベクター(1以上)を哺乳動物に直接投与する。 R1及びR2サブユニットの過剰発現は、RR複合体の形成をもたらし、続いて、dATPが産生される。 心臓機能の改善は、L48Q置換、I61Q置換又はL57Q置換されたcTnC変異体をコードする核酸配列を含むベクターの投与によっても達成され得る。 また、R1及びR2を過剰発現するドナー細胞の移植を介した、心筋にdATPをデリバリーするための組成物及び方法も提供する。 それにより、dATPはin situで産生され、ドナー細胞と宿主心筋細胞との間に確立されたギャップジャンクションを介してデリバリーされる。
【選択図】図1
11 Therapeutic agent for hepatitis c containing rrm2 antagonist as active ingredient JP2010180981 2010-08-12 JP2013223426A 2013-10-31 OBARA MICHINORI; OBARA KYOKO; SATO MASAAKI; SUDO MASAYUKI
PROBLEM TO BE SOLVED: To provide a therapeutic agent for hepatitis C containing an RRM2 antagonist as an active ingredient, an oligoribonucleotide suppressing the expression of RRM2, a vector expressing the oligonucleotide, and a method for inhibiting the expression of RRM2 by combining the oligoribonucleotide with RRM2 RNA.SOLUTION: There is identified an siRNA sequence that binds to the IRES region of HCV virus and that exhibits RNAi activity against the ribonucleotide reductase M2 subunit that has been recognized as having an important role in HCV virus replication, and then reverse transfected the siRNA into persistently HCV-infected cells and measured replicon cytotoxicity activity. As a result, the siRNA are found to exhibit significant HCV replication-suppressing activity.
12 細胞及び遺伝子に基づく心臓機能改善方法 JP2014512189 2012-05-29 JP6162104B2 2017-07-12 レグニアー、マイケル; ラフラム、マイケル; マリー、チャールズ; コート、エフ.、スティーヴン; ランディー、スコット; ハウシュカ、ステファン、デニソン; チャンバーレイン、ジェフリー、エス.; オドム、ガイ
13 nrdF JP2000552156 1999-06-01 JP2002522010A 2002-07-23 アナ・エル・コスマトカ; エドウィナ・アイ・ワイルディング; デボラ・ディ・ジャワースキー; マイケル・ティ・ブラック; リサ・ケイ・シリング; ワン・ミン
(57)【要約】 本発明はnrdFポリペプチドおよびnrdFポリペプチドをコードするポリヌクレオチドならびに組換え技法によりそのようなポリぺプチドを産生する方法を提供する。 さらに、抗菌化合物をスクリーニングするのにnrdFポリペプチドを利用する方法を提供する。
14 Suppression of malignant tumors using ribonucleotide reductase r1 JP53998798 1998-03-18 JP2002501486A 2002-01-15 エイチ ヨン,アイピン; エー ライト,ジム
(57)【要約】 本発明は、新生物細胞を、哺乳動物のリボヌクレオチドレダクターゼR1に対する発現可能核酸配列の増殖調節量と接触させることによって、ヒトまたは他の哺乳動物における細胞の悪性腫瘍性質を調節するための方法を提供する。 本発明はまた、ヒトまたは他の哺乳動物における細胞の悪性腫瘍性質を調節するための、リボヌクレオチドレダクターゼR1タンパク質または生物学的活性なペプチドの増殖調節量を提供及び使用する。 該方法は、哺乳動物リボヌクレオチドレダクターゼのR1構成要素の遺伝学的に上昇した発現を提供する。 該発現可能核酸配列は、遺伝子治療のためのベクターの形態で存在することができる。
15 METHODS AND COMPOSITIONS USEFUL IN GENERATING NON CANONICAL CD8+ T CELL RESPONSES US15549814 2016-02-10 US20180298404A1 2018-10-18 Klaus FRUEH; Louis PICKER; Scott HANSEN; Jonah SACHA; Daniel MALOULI
Methods of inducing a CD8+ T cell response to a heterologous antigen in which at least 10% of the CD8+ T cells are MHC-E restricted are disclosed. The method involves immunizing with a CMV vector that does not express UL128 and UL130 proteins. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, a UL40 protein, and a US28 protein but that do not express an active UL128 and UL130 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active UL40 protein, UL128 protein, UL130 protein, and optionally a US28 protein. Also disclosed are recombinant CMV vectors comprising nucleic acids encoding a heterologous protein antigen, but that do not express an active US28 protein, UL128 protein, UL130 protein, and optionally a UL40 protein.
16 Compositions and Methods for Inhibiting Expression of RRM2 Genes US15906054 2018-02-27 US20180195074A1 2018-07-12 John Frederick Boylan; Birgit Bramlage; Markus Hossbach; John Reidhaar-Olson
The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a RRM2 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a RRM2 gene using said pharmaceutical composition; and methods for inhibiting the expression of RRM2 in a cell.
17 Suppression of malignancy utilizing ribonucleotide reductase R1 US10223655 2002-08-20 US20030087866A1 2003-05-08 Jim A. Wright; Aiping H. Young
The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.
18 Suppression of malignancy utilizing ribonucleotide reductase R1 US09155246 1998-09-24 US06472376B2 2002-10-29 Jim A. Wright; Aiping H. Young
The present invention provides a method of modulating the malignant properties of a cell in a human or other mammal by contacting a neoplastic cell with a growth modulating amount of an expressible nucleic acid sequence for ribonucleotide reductase R1 of the mammal. The present invention also provides and uses a growth modulating amount of the ribonucleotide reductase R1 protein or biologically active peptide to modulate the malignant properties of a cell in a human or other mammal. The method provides for a generally elevated expression of the R1 component of mammalian ribonucleotide reductase. The expressible nucleic acid sequence can be in the form of a vector for gene therapy.
19 nrdF US09740452 2000-12-19 US20010010912A1 2001-08-02 Michael Terence Black; Deborah Dee Jaworski; Anna Lisa Kosmatka; Lisa Kathleen Shilling
The invention provides nrdF polypeptides and polynucleotides encoding nrdF polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdF polypeptides to screen for antibacterial compounds.
20 Ribonucleotide diphosphate reductase, nrdF, of streptococcus pneumoniae US09092437 1998-06-05 US06190881B1 2001-02-20 Michael Terence Black; Deborah Dee Jaworski; Anna Lisa Kosmatka; Lisa Kathleen Shilling; Min Wang; Edwina Imogen Wilding
The invention provides nrdF polypeptides and polynucleotides encoding nrdF polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdF polypeptides to screen for antibacterial compounds.
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