公开(公告)号：US09868937B2

公开(公告)日：2018-01-16

申请号：US14122226

申请日：2012-05-29

Applicant: Michael Regnier ,  Michael Laflamme ,  Charles Murry ,  F. Steven Korte ,  Scott Lundy ,  Stephen Denison Hauschka ,  Jeffrey S. Chamberlain ,  Guy Odom

Inventor： Michael Regnier ,  Michael Laflamme ,  Charles Murry ,  F. Steven Korte ,  Scott Lundy ,  Stephen Denison Hauschka ,  Jeffrey S. Chamberlain ,  Guy Odom

IPC: C12N5/077 ,  C12N9/02 ,  A01K67/027 ,  A61K48/00 ,  C07K14/47 ,  C12N15/85 ,  A61K9/00 ,  A61K35/34 ,  C12N7/00 ,  C12N15/86

CPC classification number: C12N5/0657 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/0375 ,  A61K9/0019 ,  A61K35/34 ,  A61K48/005 ,  C07K14/4716 ,  C12N7/00 ,  C12N9/0093 ,  C12N15/8509 ,  C12N15/86 ,  C12N2750/14132 ,  C12N2750/14143 ,  C12N2799/022 ,  C12N2799/025 ,  C12Y117/04001 ,  C12Y117/04002

Abstract: 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.

公开(公告)号：US20160186139A1

公开(公告)日：2016-06-30

申请号：US14122226

申请日：2012-05-29

Applicant: University of Washington

Inventor： Michael Regnier ,  Michael Laflamme ,  Charles Murry ,  F. Steven Korte ,  Scott Lundy ,  Stephen Denison Hauschka ,  Jeffrey S. Chamberlain

IPC: C12N5/077 ,  C12N9/02 ,  A61K48/00 ,  A61K35/34 ,  A61K9/00 ,  C12N15/86 ,  C12N7/00

CPC classification number: C12N5/0657 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/0375 ,  A61K9/0019 ,  A61K35/34 ,  A61K48/005 ,  C07K14/4716 ,  C12N7/00 ,  C12N9/0093 ,  C12N15/8509 ,  C12N15/86 ,  C12N2750/14132 ,  C12N2750/14143 ,  C12N2799/022 ,  C12N2799/025 ,  C12Y117/04001 ,  C12Y117/04002

Abstract: 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.

Abstract translation: 提供了用于改善哺乳动物心脏功能，心肌收缩力和放松的组合物和方法。 用包含核糖核苷酸还原酶亚基R1编码核酸序列的一个或多个表达载体转染的心肌细胞和可操作地连接到启动子的核糖核苷酸还原酶亚基R2-编码核酸序列的哺乳动物心肌接种。 还提供了通过移植过量表达R1和R2的供体细胞将dATP递送至心肌的组合物和方法。 因此，原位产生dATP并通过在供体细胞和宿主心肌细胞之间建立的间隙连接递送。 或者，具有R1和R2编码构建体的病毒载体直接给予哺乳动物。 通过施用包含编码L48Q，61Q或L57Q cTnC变体的核酸序列的载体也可以改善心脏功能。

公开(公告)号：US20020098544A1

公开(公告)日：2002-07-25

申请号：US09884519

申请日：2001-06-19

Inventor： Michael Terence Black

IPC: C12P021/02 ,  C07H021/04 ,  C12N009/00 ,  C12N001/21

CPC classification number: C12N9/0093 ,  A61K38/00 ,  C12Y117/04002

Abstract: The invention provides nrdG polypeptides and polynucleotides encoding nrdG polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdG polypeptides to screen for antibacterial compounds.

Abstract translation: 本发明提供nrdG多肽和编码nrdG多肽的多核苷酸以及通过重组技术产生此类多肽的方法。 还提供了利用nrdG多肽筛选抗菌化合物的方法。

公开(公告)号：US06287804B1

公开(公告)日：2001-09-11

申请号：US09040213

申请日：1998-03-17

Applicant: Michael Terence Black

Inventor： Michael Terence Black

IPC: C12P2102

CPC classification number: C12N9/0093 ,  A61K38/00 ,  C12Y117/04002

Abstract: The invention provides nrdG polypeptides and polynucleotides encoding nrdG polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing nrdG polypeptides to screen for antibacterial compounds.

Abstract translation: 本发明提供nrdG多肽和编码nrdG多肽的多核苷酸以及通过重组技术产生此类多肽的方法。 还提供了利用nrdG多肽筛选抗菌化合物的方法。