559 results about "Telomerase" patented technology

The present invention is directed to 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 present invention provides a method for diagnosing cancer, predicting a disease outcome or response to therapy in a patient sample. The method involves isolating a circulating tumor cell (CTC), for example, a viable CTC, from a sample using a parylene microfilter device comprising a membrane filter having or consisting of a parylene substrate, which has an array of holes with a predetermined shape and size; and detecting and quantifying telomerase activity in blood circulating tumor cells. The invention further provides methods of using cells live-captured in various applications.

The present invention provides methods and compositions for isolating and detecting rare cells from a biological sample containing other types of cells. In particular, the present invention includes a debulking step that uses a microfabricated filters for filtering fluid samples and the enriched rare cells can be used in a downstream process such as identifies, characterizes or even grown in culture or used in other ways. The invention also include a method of determining the aggressiveness of the tumor or of the number or proportion of cancer cells in the enriched sample by detecting the presence or amount of telomerase activity or telomerase nucleic acid or telomerase expression after enrichment of rare cells. This invention further provides an efficient and rapid method to specifically remove red blood cells as well as white blood cells from a biological sample containing at least one of each of red blood cells and white blood cells, resulting in the enrichment of rare target cells including circulating tumor cells (CTC), stromal cells, mesenchymal cells, endothelial cells, fetal cells, stem cells, non-hematopoietic cells etc from a blood sample. The method is based upon combination of immuno-microparticles (antibody coated microparticles) and density-based separation. The final enriched target cells can be subjected to a variety of analysis and manipulations, such as flowcytometry, PCR, immunofluorescence, immunocytochemistry, image analysis, enzymatic assays, gene expression profiling analysis, efficacy tests of therapeutics, culturing of enriched rare cells, and therapeutic use of enriched rare cells. In addition, depleted plasma protein and white blood cells can be optionally recovered, and subjected to other analysis such as inflammation studies, gene expression profiling, etc.

The present invention has identified compounds with extended aromatic chromophores that bind the G-quadruplex formed by the folding of single-stranded human telomeric DNA. These compounds have been shown to be effective telomerase inhibitors and are contemplated to be useful in developing cancer treatments. A model of cationic porphyrin interaction with quadruplex DNA by intercalation has been established and in combination with structure activity relations has provided novel porphyrin compounds that exhibit discrimination between binding duplex and quadruplex DNA and show improved activity against telomerase.

Novel adenovirus vectors which overexpress an adenovirus death protein and which are replication-competent in and, preferably, replication-restricted to cells expressing telomerase. One embodiment provides for efficient destruction and removal of viral-infected host cells expressing telomerase. Still further, another embodiment provides for additional restriction and safety by disrupting E1A's ability to bind p300 and / or members of the Rb family members. Compositions of the novel vectors and methods for promoting death of cells expressing telomerase with these vectors are also disclosed.

Substantially homogenous cells populations which co-express CD49c, CD90 and telomerase are made. In one embodiment, humans suffering from a degenerative, traumatic, acute injury, cardiac or neurological condition are treated with the substantially homogenous cells populations which co-express CD49c, CD90 and telomerase. In another embodiment, committed progenitor cells are made are made by selecting from a cultured source of a cell population which co-express CD49c and CD90 and modifying the cell population. The committed progenitor cells can be employed to treat a human suffering from a degenerative, traumatic, acute injury, cardiac or neurological condition and formulate pharmaceutical compositions.

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.

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 invention is directed to producing large numbers of cells using hollow fiber bioreactor technology. The cells are non-embryonic stem, non-germ cells that can be characterized by one or more of the following: extended replication in culture and markers of extended replication, such as telomerase, markers of pluripotentiality, and broad differentiation potential, without being transformed.

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.

A method for extracting antineoplastic component from Bupleurum scorzonerifolium applicable in treating cell proliferative disorder is proposed. The antineoplastic components of Bupleurum scorzonerifolium include at least a Y-butyolactone centred heterocyclic compound with a Z configuration or E configuration at its carbon 2(5) position, and molecules, such as Chaihulactone, Isochaihulactone, Chaihulactone analogues or derivatives containing in the heterocyclic compound. From results of cell and molecular biological studies, in vivo animal test, and histological study, it is found that antineoplastic components extracted from Bupleurum scorzonerifolium are effective in suppressing a variety of cancer cell growths, inhibiting telomerase activity, as well as effective in killing with high specificity Taxol-resistant tumor cells at later stage of chemical therapy, making the components a new choice for anti-cancer agent, anti-HIV agent, or synergistic agent.

Methods are disclosed for generating HLA homozygous parthenogenetic human stem cell (hpSC-Hhom) lines from both HLA homozygous and HLA heterozygous donors. These hpSC-Hhom lines demonstrate typical human embryonic stem cell morphology, expressing appropriate stem cell markers and possessing high levels of alkaline phosphatase and telomerase activity. Additionally, injection of these cell lines into immunodeficient animals leads to teratoma formation. Furthermore, in the case of HLA heterozygous donors, the hpSC-Hhom lines inherit the haplotype from only one of the donor's parents. SNP data analysis suggests that hpSC-Hhom lines derived from HLA heterozygous oocyte donors are homozygous throughout the genome as assessed by single-nucleotide polymorphism (SNP) analysis. The protocol as disclosed minimizes the use of animal-derived components, which makes the stem cells more practical for clinical application.

The invention provides methods and compositions for inhibiting telomerase activity and treatment of telomerase mediated conditions or diseases. The methods, compounds, and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents, surgery, or radiation in the treatment of conditions or diseases mediated by telomerase activity, such as in the treatment of cancer.

Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.

This invention relates to compounds, compositions, and methods useful for modulating telomerase gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of telomerase gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of telomerase genes, such as telomerase template RNA (TERC / TR), or a telomerase protein (TERT).

A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of a proteasome inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the proteasome inhibitor alone or the telomerase inhibitor alone. Preferably, efficacy is supraadditive or synergistic in nature relative to the combined effects of the individual agents, with minimal exacerbation of side effects.

The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L ("activator-antisense complex") which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

The invention discloses a colorectal cancer biomarker, relating to application of interferon-induced transmembrane protein 1 in inhibition of endogenous retrovirus in colorectal cancer. The hESCs of IFITM1-KO is constructed by using CRISPR / Cas9 technology so as to study the functions of IFITM1. Studies find that the IFITM1-deleted human embryonic stem cell (hESCs) is identical with IFITM1-WT in the aspects of cell proliferation, cell pluripotency, telomere length, telomerase activity and the like. The expression of human endogenous retrovirus in hESCs of IFITM1-KO increases, and expression in para-carcinoma tissue is higher than that in colorectal carcinoma tissue. ChIP-qPCR detection finds that the enrichment of H3K9me3 in hESCs of IFITM1-KO is reduced at the HERVs site. Data shows that the expression level of IFITM1 in hESCs and colorectal carcinoma is in negative correlation to HERVs expression, and the IFITM1 can inhibit the expression of HERVs by regulating epigenetic inheritance.

The present invention relates to a method of immortalizing progenitor cells by providing a population of progenitor cells (e.g, neural progenitor cells) and immortalizing the progenitor cells either before or after they are enriched or purified. The present invention is also directed to an enriched or purified population of immortalized progenitor cells (e.g., neural progenitor cells).

The invention provides methods and compositions relating to discrete elements of human telomerase and human telomerase RNA. In one embodiment, the invention provides a polynucleotide comprising only one element of human telomerase RNA, wherein the element consists of SEQ ID NO:1, residues 241-330. Such human telomerase RNA elements may be employed in mixtures with a human telomerase polypeptide such as TERT or dyskerin, wherein the polypeptide and polynucleotide specifically interact, and such mixtures may be employed in methods for identifying modulators of a human telomerase polypeptide-human telomerase RNA interaction.

Nucleic acid molecules encoding vertebrate telomerase are provided. Gene products, expression vectors and host cells suitable for expressing telomerase are also provided. Methods for identifying inhibitors of telomerase activity and inhibitor compositions are disclosed.

Non-embryonic blastomere-like totipotent stem cells are disclosed. Most preferably, such cells are obtained from various tissues of postnatal mammals (e.g., using tissue biopsied from the mammal), are smaller than 1 μm, have normal karyotype, and do not spontaneously differentiate in serum-free medium without differentiation inhibitors. These non-embryonic blastomere-like totipotent stem cells typically express CD66e, CEA-CAM-1 and telomerase, but do not typically express CD10, SSEA-1, SSEA-3, and SSEA-4. Such blastomere-like totipotent cells can be differentiated into ectodermal, mesodermal, or endodermal tissues, including placental tissues and germ cells. Moreover, when implanted into a mammal, such cells will not be teratogenic.

The present invention provides a reagent for cancer cell detection or cancer diagnosis. The present invention relates to a reagent for cancer cell detection, comprising a recombinant virus where a replication cassette comprising a promoter from human telomerase, an E1A gene, an IRES sequence and an E1B gene in this order is integrated in E1 region of the viral genome and a labeling cassette comprising a gene encoding a labeling protein and a promoter capable of regulating the expression of the gene encoding the labeling protein is integrated in E3 region of the viral genome.

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.

A primer for the amplification of a DNA template comprising a protelomerase target sequence, particularly for production of closed linear DNA, which primer is capable of specifically binding to a palindromic sequence within a protelomerase target sequence and priming amplification in both directions.

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 invention discloses a method for quantitatively detecting telomerase activity based on a nano pore channel and electrochemical sensing.The method comprises the following steps that firstly, a telomerase recognition sequence is connected to the inner wall of a porous anodic alumina template or a polyethylene terephthalate film to serve as a primer; secondly, telomerase amplifies the primer to form a G-rich sequence; a G-quadruplex is formed in the presence of potassium ions; electrochemical detection is conducted on the current produced through indicating molecules of the nano pore channel by utilizing an electrochemical workstation.The method does not need complex material preparation and DNA probe marking, and can avoid the defects of high detection cost, complicated operation and poor reproducibility caused by the complex material preparation and DNA probe marking and has the advantages of being low in cost, quick, simple, convenient, high in sensitivity and good in accuracy.