Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes.
Type:
Grant
Filed:
February 1, 2002
Date of Patent:
November 11, 2003
Assignee:
The Board of Trustees of the Leland Stanford Junior
University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: The present invention is directed to an isoform of the p53 tumor suppressor and to polynucleotides that encode this isoform. The isoform may be used as a marker to indicate that cardiac cells have experienced hypoxia, as would occur during a myocardial infarction. In addition, vectors encoding the isoform may be transfected into cells as a means of regulating proliferation.
Type:
Grant
Filed:
October 7, 1999
Date of Patent:
September 25, 2001
Assignee:
The Brigham and Women's Hospital Inc.
Inventors:
Giorgio Dell'Acqua, Michael J. Mann, Victor J. Dzau
Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes.
Type:
Grant
Filed:
August 15, 2001
Date of Patent:
November 4, 2003
Assignee:
The Board of Trustees of the Leland Stanford Junior
University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: The present disclosure provides compositions and methods for the reprogramming of cells such as fibroblasts into cardiomyocytes. The invention provided herein features a chemically defined media and methods of reprogramming cells to increase cardiac gene and protein expression in cardiac fibroblasts and other fibroblasts, e.g. dermal fibroblasts. The media and methods also enhance miR-combo mediated cardiac reprogramming of fibroblasts to cardiomyocytes. Thus, the invention encompasses a chemically defined reprogramming media comprising a base tissue culture media, insulin-transferrin-selenium (ITS) or ascorbic acid in a somatic cell-reprogramming, e.g., fibroblast-to-cardiomyocyte-reprogramming, amount.
Type:
Application
Filed:
June 20, 2019
Publication date:
January 9, 2020
Inventors:
Xiaowen Wang, Conrad P. Hodgkinson, Victor Dzau
Abstract: The present disclosure provides compositions and methods for the reprogramming of cells such as fibroblasts into cardiomyocytes. The invention provided herein features a chemically defined media and methods of reprogramming cells to increase cardiac gene and protein expression in cardiac fibroblasts and other fibroblasts, e.g. dermal fibroblasts. The media and methods also enhance miR-combo mediated cardiac reprogramming of fibroblasts to cardiomyocytes. Thus, the invention encompasses a chemically defined reprogramming media comprising a base tissue culture media, insulin-transferrin-selenium (ITS) or ascorbic acid in a somatic cell-reprogramming, e.g., fibroblast-to-cardiomyocyte-reprogramming, amount.
Type:
Application
Filed:
August 7, 2015
Publication date:
February 15, 2018
Inventors:
Xiaowen Wang, Conrad P. Hodgkinson, Victor Dzau
Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host.
Type:
Grant
Filed:
May 8, 1998
Date of Patent:
January 8, 2002
Assignee:
The Board of Trustees of the Leland Stanford Junior
University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds, namely L-arginine, L-lysine, physiologically acceptable salts thereof, and polypeptide precursors thereof, which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. In or in combination, other compounds, such as B.sub.6, folate, B.sub.12, or an antioxidant, which provide for short term enhancement of nitric oxide, either directly or by physiological processes may be employed.
Type:
Application
Filed:
February 1, 2002
Publication date:
October 17, 2002
Applicant:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
John
P.
COOKE
, Victor
J.
DZAU
, Gary
H.
GIBBONS
Abstract: Atherogenesis and restenosis are treated by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes. In addition, cells may be genetically engineered to provide a component in the synthetic pathway to nitric oxide, so as drive the process to enhance nitric oxide concentration, particularly in conjunction with the administration of a nitric oxide precursor.
Type:
Grant
Filed:
June 11, 1993
Date of Patent:
June 27, 1995
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: A method of enhancing injury-induced revascularization of a tissue as treatment of a disease, such as coronary artery disease, is described. The method involves (i) creating injury in a tissue (e.g., muscle, such as cardiac muscle) by, for example, use of a laser, an ultrasonic device, or a Thermal probe, and (ii) injecting into the tissue a revascularization-promoting molecule or a nucleic acid molecule encoding a revascularization-promoting molecules Also described is an apparatus that can be used to practice this method.
Type:
Grant
Filed:
March 27, 1998
Date of Patent:
March 13, 2001
Assignee:
The Brigham and Women's Hospital, Inc.
Inventors:
Michael J. Mann, Umer Sayeed-Shah, Victor Dzau, Lawrence H. Cohn
Abstract: Methods and compositions are provided for intracellular transfer of a wide variety of agents, by using Sendai virus comprising liposomes having various compositions in the liposome lumen. A preferred method for preparing the liposomes provides for enhanced levels of luminal concentrations, as well as incorporation of high molecular weight molecules. The method comprises fusing liposomes, where one liposome comprises the Sendai virus proteins and the other liposome comprises the luminal composition. The subject methods find particular application with intranuclear transfer of nucleic acids, more particularly with cells of the vasculature.
Abstract: Disclosed herein is a method for implanting cells onto a prosthesis, including the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. Also disclosed herein are methods for culturing cells for implantation.
Type:
Application
Filed:
January 18, 2002
Publication date:
May 16, 2002
Inventors:
Victor J. Dzau, Richard E. Pratt, Michael J. Mann, Afshin Ehsan, Daniel P. Griese
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Application
Filed:
April 25, 2003
Publication date:
October 2, 2003
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signaling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Application
Filed:
June 5, 2001
Publication date:
September 12, 2002
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Application
Filed:
May 20, 2004
Publication date:
November 18, 2004
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita
Abstract: Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds, namely L-arginine, L-lysine, physiologically acceptable salts thereof, and polypeptide precursors thereof, which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. In or in combination, other compounds, such as B.sub.6, folate, B.sub.12, or an antioxidant, which provide for short term enhancement of nitric oxide, either directly or by physiological processes may be employed.
Type:
Grant
Filed:
November 9, 1995
Date of Patent:
April 6, 1999
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Application
Filed:
April 19, 2001
Publication date:
May 2, 2002
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita
Abstract: Atherogenesis and restenosis are treated by long term administration of physiologically acceptable compounds which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. Alternatively, or in combination, other compounds may be administered which provide for short term enhancement of nitric oxide, either directly or by physiological processes. In addition, cells may be genetically engineered to provide a component in the synthetic pathway to nitric oxide, so as to drive the process to enhance nitric oxide concentration, particularly in conjunction with the administration of a nitric oxide precursor.
Type:
Grant
Filed:
February 7, 1997
Date of Patent:
August 31, 1999
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
John P. Cooke, Victor J. Dzau, Gary H. Gibbons
Abstract: Disclosed herein is a method for implanting cells onto a prosthesis, including the steps of: (a) providing a prosthesis including a porous tube, where at least 25% of the pores on the inner surface of the tube have diameters of more than about 40 &mgr;m, at least 25% of the pores on the outer surface of the tube have diameters of less than about 30 &mgr;m, and the tube includes a substantially continuous layer of a biocompatible material; (b) contacting the prosthesis with a suspension of cells; and (c) providing a pressure differential between the inner surface and the outer surface, whereby the cells are retained in the pores of the inner surface. Also disclosed herein are methods for culturing cells for implantation.
Type:
Grant
Filed:
July 8, 1999
Date of Patent:
March 5, 2002
Assignee:
The Brigham and Womens Hospital, Inc.
Inventors:
Victor J. Dzau, Richard E. Pratt, Michael J. Mann, Afshin Ehsan, Daniel P. Griese
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Grant
Filed:
September 8, 1995
Date of Patent:
August 10, 2004
Assignee:
The Brigham and Women's Hospital, Inc.
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita
Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.
Type:
Grant
Filed:
April 19, 2001
Date of Patent:
November 23, 2004
Assignee:
The Brigham and Women's Hospital, Inc.
Inventors:
Victor J. Dzau, Gary H. Gibbons, Ryuichi Morishita