Abstract: A new protein named Tankyrase II is described in this disclosure. Sequences for the human Tankyrase II cDNA and the protein translation product are provided. Also provided are species homologs, muteins, related nucleic acids, peptides, and drug screening assays. Tankyrase II interacts with telomere-associated proteins, thereby affecting telomerase activity and potentially telomere length. The materials and techniques provided in this disclosure allow Tankyrase II activity to be studied in vitro and manipulated inside cells—to the potential benefit of clinical conditions associated with a defect in telomerase activity, or the replicative capacity of affected cells.

Abstract: This invention provides a system for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable. The cells contain an effector gene under control of a transcriptional control element (such as the TERT promoter) that causes the gene to be expressed in relatively undifferentiated cells in the population. Expression of the effector gene results in depletion of undifferentiated cells, or expression of a marker that can be used to remove them later. Suitable effector sequences encode a toxin, a protein that induces apoptosis, a cell-surface antigen, or an enzyme (such as thymidine kinase) that converts a prodrug into a substance that is lethal to the cell. The differentiated cell populations produced according to this disclosure are suitable for use in tissue regeneration, and non-therapeutic applications such as drug screening.

Abstract: An optimum time has been discovered for obtaining porcine oocytes with improved developmental competence. Harvested oocytes are matured by culturing in vitro, and then activated ˜42-46 hours after beginning of the culture period. Alternatively, ovulation is induced in a donor female using a gonadotrophic hormone (optionally monitored by ultrasonography), maturation is allowed to proceed in vivo, and then the harvested oocyte is activated ˜44-48 hours after inducing ovulation. Outside the optimal time frame, the ability of the oocytes to undergo parthenogenetic activation declines markedly. These methods overcome problems encountered with previous protocols for nuclear transfer and assisted reproduction in the pig.

Abstract: This invention provides purified telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of matrices that bind molecules bearing negative charges, matrices that bind molecules bearing positive charges, intermediate-selectivity matrices, methods that separate molecules based on their size, shape, or buoyant density, and by affinity purification.

Abstract: This invention provides purified telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of matrices that bind molecules bearing negative charges, matrices that bind molecules bearing positive charges, intermediate-selectivity matrices, methods that separate molecules based on their size, shape, or buoyant density, and by affinity purification.

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.

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: 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.

Abstract: Thiazolidinedione compounds, compositions, and methods of inhibiting telomerase activity in vitro and treatment of telomerase mediated conditions or diseases ex vivo and in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of conditions or diseases mediated by telomerase activity, such as in the treatment of cancer. Also disclosed are methods for assaying or screening for inhibitors of telomerase activity.

Abstract: The present invention 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.

Abstract: The invention provides a method of 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 a 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: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. Catalytically active human telomerase reverse transcriptase variants comprising deletions or other mutations are provided.

Abstract: Purified and recombinant proteins TPC2 and TPC3 and recombinant or synthetic oligonucleotides corresponding to those proteins or fragments thereof can be used to detect regulators of telomere length and telomerase activity in mammalian cells and for a variety of related diagnostic and therapeutic purposes.

Abstract: This invention provides purified human telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of a first matrix that binds molecules bearing negative charges, a matrix that binds molecules bearing positive charges, a second matrix that binds molecules bearing negative charges, an affinity purification step and a matrix that separates molecules according to their size.