Abstract: This invention provides populations human cells of the cardiomyocyte lineage. The cells are obtained by causing cultures of pluripotent stem cells to differentiate in vitro, and then harvesting cells with certain phenotypic features. Differentiated cells bear cell surface and morphologic markers characteristic of cardiomyocytes, and a proportion of them undergo spontaneous periodic contraction. Highly enriched populations of cardiomyocytes and their replicating precursors can be obtained, suitable for use in a variety of applications, such as drug screening and therapy for cardiac disease.
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Grant
Filed:
June 24, 2004
Date of Patent:
August 19, 2008
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: This disclosure provides a system for obtaining genetically altered primate pluripotent stem (pPS) cells. The role of the feeder cells is replaced by supporting the culture on an extracellular matrix, and culturing the cells in a conditioned medium. The cells can be genetically altered with a viral vector or DNA/lipid complex, and then selected for successful transfection by drug-resistant phenotype in the transfected cells. The system allows for bulk proliferation of genetically altered pPS cells as important products for use in human therapy or drug screening.
Type:
Grant
Filed:
September 24, 2004
Date of Patent:
August 19, 2008
Assignee:
Geron Corporation
Inventors:
Joseph D. Gold, Melissa K. Carpenter, Margaret S. Inokuma, Chunhui Xu
Abstract: Methods and materials for culturing primate-derived primordial stem cells are described. In one embodiment, a cell culture medium for growing primate-derived primordial stem cells in a substantially undifferentiated state is provided which includes a low osmotic pressure, low endotoxin basic medium that is effective to support the growth of primate-derived primordial stem cells. The basic medium is combined with a nutrient serum effective to support the growth of primate-derived primordial stem cells and a substrate selected from feeder cells and an extracellular matrix component derived from feeder cells. The medium further includes non-essential amino acids, an anti-oxidant, and a first growth factor selected from nucleosides and a pyruvate salt.
Type:
Grant
Filed:
December 24, 2002
Date of Patent:
August 19, 2008
Assignee:
Geron Corporation
Inventors:
Andrea G. Bodnar, Choy-Pik Chiu, Joseph D. Gold, Margaret Inokuma, James T. Murai, Michael D. West
Abstract: This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
Type:
Grant
Filed:
September 4, 2002
Date of Patent:
August 12, 2008
Assignee:
Geron Corporation
Inventors:
Ramkumar Mandalam, Chunhui Xu, Joseph D. Gold, Melissa K. Carpenter
Abstract: The invention provides a method for activating a T lymphocyte by contacting the T lymphocyte with a dendritic cell (DC) that presents a telomerase reverse transcriptase (TRT) peptide in the context of an MHC class I or MHC class II molecule. The DC may be pulsed with a TRT polypeptide or may comprise a recombinant polynucleotide encoding a TRT such as hTRT. The invention also provides DCs comprising a recombinant TRT polynucleotide. The methods and compositions of the invention are used in prevention and treatment of cancers and other cell proliferation diseases or conditions.
Abstract: Telomerase reverse transcriptase is part of the telomerase complex responsible for maintaining telomere length and increasing the replicative capacity of progenitor cells. Telomerase activity is turned off in mature differentiated cells, but is turned back on again in hyperplastic diseases, including many cancers. This disclosure provides regulatory elements that promote transcription in cells that express telomerase reverse transcriptase (TERT). The disclosure also provides systems using TERT promoter sequences for identifying compounds that can be used to modulate telomerase expression.
Type:
Grant
Filed:
April 25, 2006
Date of Patent:
May 27, 2008
Assignee:
Geron Corporation
Inventors:
Gregg B. Morin, Serge Lichtsteiner, Alain Vasserot, Robert Adams, William H. Andrews
Abstract: This disclosure provides a system for producing pancreatic islet cells from embryonic stem cells. Differentiation is initiated towards endoderm cells, and focused using reagents that promote emergence of islet precursors and mature insulin-secreting cells. High quality populations of islet cells can be produced in commercial quantities for use in research, drug screening, or regenerative medicine.
Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(—O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-arabino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.
Abstract: This disclosure provides TRT antisense oligonucleotides, methods of detecting TRT, methods of diagnosing telomerase-related conditions, methods of diagnosing and providing a prognosis for cancer, and methods of treating telomerase-related conditions, including cancer.
Type:
Grant
Filed:
August 8, 2003
Date of Patent:
November 20, 2007
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: This disclosure provides an improved system for culturing human pluripotent stem cells. Traditionally, pluripotent stem cells are cultured on a layer of feeder cells (such as mouse embryonic fibroblasts) to prevent them from differentiating. In the system described here, the role of feeder cells is replaced by components added to the culture environment that support rapid proliferation without differentiation. Effective features are a suitable support structure for the cells, and an effective medium that can be added fresh to the culture without being preconditioned by another cell type. Culturing human embryonic stem cells in fresh medium according to this invention causes the cells to expand surprisingly rapidly, while retaining the ability to differentiate into cells representing all three embryonic germ layers. This new culture system allows for bulk proliferation of pPS cells for commercial production of important products for use in drug screening and human therapy.
Abstract: The present invention is directed to monoclonal or recombinant antibodies or fragments thereof that bind to human telomerase reverse transcriptase (hTRT) protein. The present invention is also directed to methods of identifying or detecting hTRT polypeptides in biological samples. The invention is further directed to methods of generating antibodies that specifically bind to hTRT protein.
Type:
Grant
Filed:
January 18, 2002
Date of Patent:
October 23, 2007
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function.
Type:
Grant
Filed:
March 1, 2002
Date of Patent:
October 16, 2007
Assignee:
Geron Corporation
Inventors:
Lakshmi Rambhatla, Melissa K. Carpenter
Abstract: It has been discovered that increasing telomerase activity in cells surrounding a wound has a variety of effects that enhance wound healing. Replication capacity is enhanced, and the mobility of the epithelial cells can be increased by 3-fold or more. Some aspects of the invention relate to agents that increase telomerase activity in cells at the site of the wound, promoting cells to move to the site and restore an epithelial layer and the underlying stratum. Other aspects of the invention relate to compositions comprising epithelial cells in which telomerase activity has been increased, useful as grafts for the treatment of wounds.
Type:
Grant
Filed:
May 9, 2002
Date of Patent:
August 28, 2007
Assignee:
Geron Corporation
Inventors:
Xu-Rong Jiang, Choy-Pik Chiu, Calvin B. Harley
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Grant
Filed:
November 22, 2000
Date of Patent:
August 28, 2007
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function.
Type:
Grant
Filed:
October 31, 2001
Date of Patent:
August 14, 2007
Assignee:
Geron Corporation
Inventors:
Lakshmi Rambhatla, Melissa K. Carpenter
Abstract: This invention provides populations of neural progenitor cells and differentiated neurons, obtained by culturing pluripotent cells in special growth cocktails. The technology can be used to produce progenitors that proliferate through at least ˜40 doublings, while maintaining the ability to differentiate into a variety of different neural phenotypes, including dopaminergic neurons. The neural progenitors and terminally differentiated neurons of this invention can be generated in large quantities for use in drug screening and the treatment of neurological disorders.
Type:
Grant
Filed:
May 28, 2002
Date of Patent:
July 31, 2007
Assignee:
Geron Corporation
Inventors:
Melissa K. Carpenter, Jerrod J. Denham, Margaret S. Inokuma, R. Scott Thies
Abstract: Formulations containing plant extracts, in particular Astragalus extracts, and their use in inducing telomerase activity in cells, are described. Such compositions include pharmaceutical, including topical, and nutraceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in selected cells, such as, for example, HIV infection, various degenerative diseases, and acute or chronic skin ailments. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and proliferation of stem cells. Also described are cosmetic formulations of such extracts for conditioning the skin.
Type:
Application
Filed:
June 25, 2004
Publication date:
May 31, 2007
Applicants:
Hong Kong University of Science and Technology, Geron Corporation
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Abstract: The present invention is directed to cells comprising a recombinant polynucleotide sequence that encodes a telomerase reverse transcriptase protein, variant, or fragment having telomerase catalytic activity when complexed with a telomerase RNA.
Type:
Grant
Filed:
January 11, 2002
Date of Patent:
March 27, 2007
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews