127 results about "Human telomerase" patented technology

Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

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.

A therapeutic compound consisting of human telomerase, its catalytic subunit hTert, or a known variant of either, and a biodegradable nanoparticle carrier, which can be administered to cells in a cell culture or in a living animal, is provided herein. The therapeutic compound is envisioned as a method for treating a wide variety of age-related diseases such as idiopathic pulmonary fibrosis, aplastic anemia, dyskeratosis congenita, arteriosclerosis, macular degeneration, osteoporosis, Alzheimer's, diabetes type 2, and any disease that correlates with telomere shortening and may be corrected or ameliorated by lengthening telomeres. The therapeutic compound is also envisioned as method for potentially treating more generic problems of human aging. The nanoparticle carrier is comprised of certain biodegradable biocompatible polymers such as poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), poly-allylamine, polyanhydride, polyhydroxybutyric acid, polycaprolactone, lactide-caprolactone copolymers, polyhydroxybutyrate, polyalkylcyanoacrylates, polyanhydrides, polyorthoester or a combination thereof. The nanoparticle may incorporate a targeting moiety to direct the nanoparticle to a particular tissue type or a location within a cell. The nanoparticle may incorporate a plasticizer to facilitate sustained release of telomerase such as L-tartaric acid dimethyl ester, triethyl citrate, or glyceryl triacetate. A nanoparticle of the present invention can further contain a polymer that affects the charge or lipophilicity or hydrophilicity of the particle. Any biocompatible hydrophilic polymer can be used for this purpose, including but not limited to, poly(vinyl alcohol).

The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.

The invention provides a eukaryotic expression vector for expressing shRNA (short hairpin Ribonucleic Acid) in manner of targeting in cancer cells, comprising the structure as follows: (1) an expression cassette structure which is driven by a polII-type promoter and connects a fluorescent protein gene and a mirshRNA structure in series together; (2) a hTERT (human telomerase reverse transcriptase) promoter enhanced by a CMV (cytomegalovirus) enhancer and a SV40 (simian virus 40) enhancer; (3) mirshRNA structures based on mir30: mir30 left arm-shRNA-mir30 right arm, and multiple mirshRNA structures can be connected in series; (4) a Kan or Amp resistance selection marker; and (5) LR homologous recombination arms. By utilizing the method to construct the shRNA eukaryotic expression vector, one or more than one shRNA can be specifically expressed in the cancer cells in manner of targeting; normal cells are not influenced while the RNA interference and the gene therapy are carried out on the cancer cells, thereby solving the problem of non-specific interference during carrying out the gene therapy by utilizing the RNA interference and being beneficial to the research and the application of the RNA interference in the cancer gene therapy aspect.

The present invention is directed to a novel variant of human telomerase reverse transcriptase (S16AhTERT), which displays properties distinct from those of wildtype telomerase reverse transcriptase. Accordingly, the amino acid sequence of S16AhTERT and nucleic acid sequences encoding same are presented herein, as are methods of use thereof.

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.

The invention provides compositions comprising fragments of human telomerase reverse transcriptase (hTERT) which can lead to telomere dysfunction in a cell and reduction of growth and tumorigenicity in cancer cells. The invention also relates to uses of the fragments in the treatment of cancer and in drug discovery.

We report the use of telomerase-immortalized human microvascular endothelial cells in the formation of functional capillary blood vessels in vivo. Previously we showed the superior in vitro survival of human telomerase reverse transcriptase (hTERT)-transduced human endothelial cells. Here we show that retroviral-mediated transduction of hTERT in human dermal microvascular endothelial cells (HDMEC) results in cell lines that form microvascular structures when subcutaneously implanted in severe combined immunodeficiency (SCID) mice. The human origin of xenografted microvaculature was confirmed both by basement membrane immunoreactivity with anti-human type IV collagen staining and visualization of fluorescent vessels containing HDMEC that were co-transduced with hTERT and green fluorescent protein (eGFP). The lack of human vascular structures after implantation of HT1080 fibrosarcoma cells, 293 human embryonic kidney cells or human skin fibroblasts demonstrated the specificity of HDMEC at forming capillaries. Intravascular red fluorescent microspheres injected into the host circulation were found within green “telomerized” microvessels indicating functional murine-human vessel anastamoses. Whereas primary HDMEC-derived vessel density decreased steadily with time, telomerized HDMEC maintained durable vessels 6 weeks after xenografting. Modulation of implant vessel density by exposure to different angiogenic and angiostatic factors demonstrated the utility of this system for the study of human microvascular remodeling in vivo.