686 results about "Tissue specific" patented technology

The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and / or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and / or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and / or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention also has important implications in the eradication of drug-resistant pathogens and drug-resistant diseased cells (such as cancer cells).

Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin(TM), interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and / or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.

Cell-penetrating peptides useful for targeting a therapeutic compound to a selected mammalian tissue, methods for their identification, methods of forming conjugate compounds containing such peptides, and conjugates formed thereby are disclosed. The cell-penetrating peptides are 8 to 30 amino acid residues in length and consist of subsequences selected from the group consisting of RXR, RX, RB, and RBR; where R is arginine, B is β-alanine, and each X is independently —C(O)—(CHR1)n—NH—, where n is 4-6 and each R1 is independently H or methyl, such that at most two R1's are methyl. In one embodiment, X is a 6-aminohexanoic acid residue.

The subject invention concerns materials and methods for controlling agricultural traits in plants that are mediated by the plant hormone ethylene. One aspect of the invention concerns a polynucleotide that comprises a sequence encoding a mutant ethylene receptor that is operably linked to a regulatory sequence that drives expression of the mutant receptor in a tissue-specific manner. In an exemplified embodiment, the mutant receptor sequence is an etr1-1 sequence, or a functional fragment or variant thereof, and the regulatory sequence is a promoter sequence from a cotton chitinase gene that can promote expression of the mutant ethylene receptor in abscission zone tissue of a plant. The subject invention also concerns plants and plant tissue transformed with the polynucleotide of the subject invention. Plants expressing the polynucleotide of the subject invention do not drop their flowers in response to exposure to ethylene.

The present invention relates to methods and devices for delivering one or more biologically active agents, particularly a diagnostic agent to the intradermal compartment of a subject's skin. The present invention provides an improved method of delivery of biologically active agents in that it provides among other benefits, rapid uptake into the local lymphatics, improved targeting to a particular tissue, improved bioavailability, improved tissue bioavailability, improved tissue specific kinetics, improved deposition of a pre-selected volume of the agent to be administered, and rapid biological and pharmacodynamics and biological and pharmacokinetics. This invention provides methods for rapid transport of agents through lymphatic vasculature accessed by intradermal delivery of the agent. Methods of the invention are particularly useful for delivery of diagnostic agents.

The present teachings provide methods for diagnosing biological conditions, including cancer. In some embodiments, a test sample is collected from a subject such as a clinical patient, wherein the test sample comprises background tissue and may or may not contain cells from a tissue of interest. Observation of a target miRNA normally present in a tissue of interest, but collected in an anatomical location ectopic to the tissue of interest, can be indicative of a biological condition. The present teachings further provide exponential amplification techniques applicable to performing these analyses.

The present invention relates to conjugates of a lipid, substrate peptide of an enzyme secreted from the cells of mammals, including humans, and a water-soluble polymer that can be used as colloidal carriers and the like of tissue-specific drug delivery systems, methods of producing these conjugates, peptide-water-soluble polymer conjugates optionally having protective groups that are useful as the intermediates of these conjugates, colloidal carriers made from these conjugates, and tissue-specific drug delivery systems that use these colloidal carriers.

This invention relates to a lamellae tissue layer, comprising a grooved silk fibroin substrate comprising tissue-specific cells. The silk fibroin substrates provides an excellent means of controlling and culturing cell and extracellular matrix development. A multitude of lamellae tissue layers can be used to create a tissue-engineered organ, such as a tissue-engineered cornea. The tissue-engineered organ is non-immunogenic and biocompatible.

The invention relates to plant transcription factor polypeptides, polynucleotides that encode them, homologs from a variety of plant species, and methods of using the polynucleotides and polypeptides to produce transgenic plants having advantageous properties, including increased soluble solids, lycopene, and improved plant volume or yield, as compared to wild-type or control plants. The invention also pertains to expression systems that may be used to regulate these transcription factor polynucleotides, providing constitutive, transient, inducible and tissue-specific regulation.

The present invention relates to formulations, methods and devices for delivering one or more biologically active agents, particularly a diagnostic or therapeutic agent to the intradermal compartment of a subject's skin. The present invention provides an improved method of delivery of biologically active agents in that it provides among other benefits, rapid uptake into the local lymphatics, improved targeting to a particular tissue, improved bioavailability, improved tissue bioavailability, improved tissue specific kinetics, improved deposition of a pre-selected volume of the agent to be administered. This invention provides methods for rapid transport of agents through lymphatic vasculature accessed by intradermal delivery of the agent. Methods of the invention are particularly useful for delivery of diagnostic and therapeutic agents. The invention relates to the synergy gained in diagnosing and treating disease when intradermal delivery and controlled release materials are combined. Specifically, the synergy is achieved when intradermal delivery is combined with lipid based particles.

Tolerogenic populations of dendritic cells are provided, where the dendritic cells are characterized by expression of select tissue-specific homing receptors including the chemokine receptors CCR9; or CMKLR1; or the integrin CD103. The dendritic cells may be conventional / myeloid or plasmacytoid dendritic cells. The cells may be isolated from lymphoid tissue, from blood, or from in vitro culture, e.g. bone marrow culture, etc. Methods are provided for their identification, isolation and targeting in immunotherapeutic interventions in suppressing inflammatory disorders including autoimmunity, transplantation responses and allergic diseases. In some embodiments dendritic cell populations are fixed to render them immunosuppressive, thus allowing the cells to be typed and banked for future use.

The contributions of different tissues to a DNA mixture are determined using methylation levels at particular genomic sites. Tissue-specific methylation levels of M tissue types can be used to deconvolve mixture methylation levels measured in the DNA mixture, to determine fraction contributions of each of the M tissue types. Various types of genomic sites can be chosen to have particular properties across tissue types and across individuals, so as to provide increased accuracy in determining contributions of the various tissue types. The fractional contributions can be used to detect abnormal contributions of a particular tissue, indicating a disease state for the tissue. A differential in fractional contributions for different sizes of DNA fragments can also be used to identify a diseased state of a particular tissue. A sequence imbalance for a particular chromosomal region can be detected in a particular tissue, e.g., identifying a location of a tumor.

The invention relates to plant transcription factor polypeptides, polynucleotides that encode them, homologs from a variety of plant species, and methods of using the polynucleotides and polypeptides to produce transgenic plants having advantageous properties, including increased biomass or improved cold or other osmotic stress tolerance, as compared to wild-type or reference plants. The invention also pertains to expression systems that may be used to regulate these transcription factor polynucleotides, providing constitutive, transient, inducible and tissue-specific regulation.

The present invention provides functionalized magnetic nanoparticles comprising a functional group, which functionalized magnetic nanoparticles exhibit differential binding to a tissue, indulging brain tissue, bone, and vascular tissues. The present invention further provides compositions, including pharmaceutical compostions, comprising a subject functionalized magnetic nanoparticle. The present invention further provides diagnostic and research methods including use of subject functionized magnetic nanoparticles. The present invention further provides a magnetic resonance imaging (MRI)-visible drug delivery system; drugs using MRI, as well as tissue-specific drug delivery.

Recombinant lentiviruses and transfer vectors for transgene delivery as well as methods for gene therapy using such vectors are disclosed. The invention provides a third generation lentiviral packaging system and a set of vectors for producing recombinant lentiviruses, as well as novel tissue specific enhancer and promoter elements useful for optimizing liver specific transgene delivery. The transgene is preferably a blood clotting factor such as human factor IX (hFIX) or human factor VIII (hFVIII) and can be used for treatment of hemophilia.

Antibodies and molecules derived therefrom that bind to 161P2F10B protein and variants thereof, are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 161P2F10B provides a diagnostic, prognostic, prophylactic and / or therapeutic target for cancer. The 161P2F10B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 161P2F10B can be used in active or passive immunization.

A novel cell seeded hollow fiber bioreactor is described as a potential bioartificial kidney. Endothelial cells along with pericyte, vascular smooth muscle, and / or mesangial cells or any mesenchymally derived support cells are seeded along a hollow fiber in a perfused bioreactor to reproduce the ultrafiltration function and transport function of the kidney. Maintenance of tissue specific function and ultrastructure suggest that this bioreactor provides an economical device for treating renal failure.

Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

Methods of delivering an agent in a tissue-specific manner, particularly lung tissue, by targeting a protein expressed on the endothelial cell surface, are described. The methods can be used for detecting, imaging and / or treating pathologies, as well as for diagnostics.

The present invention provides for the expression of phytase in transgenic plants or plant organs and methods for the production of such plants. DNA expression constructs are provided for the transformation of plants with a gene encoding phytase under the control of regulatory sequences which are capable of directing the expression of phytase. These regulatory sequences include sequences capable of directing transcription in plants, either constitutively, or stage and / or tissue specific, depending on the use of the plant or parts thereof. The transgenic plants and plant organs provided by the present invention may be applied to a variety of industrial processes either directly, e.g. in animal feeds or alternatively, the expressed phytase may be extracted and if desired, purified before application.

Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin(TM), interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and / or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.

The invention is directed to isolated promoters from stem-regulated, defense-inducible genes, such as JAS promoters. The promoters are useful in expression cassettes and expression vectors for the transformation of plants. Particularly, the invention provides transgenic plants of rice and sugarcane that have been modified such that expression of a heterologous coding sequence is directed by an JAS promoter and is limited to stem tissues or may be upregulated by the presence of a defense-inducing agent. The invention also discloses methods for producing the expression vectors and transgenic plants.

Described are non-invasive methods of detecting in vivo cell death by measuring levels of ubiquitous and tissue specific miRNA. The method can be applied for detection of pathologies caused or accompanied by cell death, as well as for diagnosis of infectious disease, cytotoxic effects induced by different chemical or physical factors, and the presence of specific fetal abnormalities.

A method of ascertaining the bio-safety of an agent is disclosed. The method comprises:(a) contacting the agent with differentiating human pluripotent stem cells;(b) analyzing a level of gene expression of a plurality of genes in the differentiating human pluripotent stem cells, wherein the agent is qualified as being safe if at least one of the following qualification parameters are fulfilled:(i) the agent causes a difference in the level of gene expression below a predetermined number of genes as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent;(ii) the agent causes a difference in gene expression below a predetermined number of tissue-specific genes of a tissue as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent; or(iii) the agent causes a difference in gene expression below a predetermined number of genes involved in fetal development as compared to control differentiating human pluripotent stem cells that have not been contacted with the agent.

The invention relates to a method using three-dimensional mechanics characteristics and tissue specific imaging of blood vessels and plaques for detection. The method is on the basis of a multi-beam focus wave and superfast plane wave alternative transmitting sequence and can also be extended to a line-by-line scan imaging manner; the forms and the functions of the blood vessels and the plaques are evaluated and imaged respectively from the aspects of the radial-direction, circumferential and axial-direction three-dimensional mechanics characteristics, blood vessel wall shear rate, plaque form and tissue characterization, and the like; the new method which is provided for detection of the vulnerable plaques of a carotid artery is regarded as the improvement of the existing method.

A laser system that includes a diode pump source. A frequency doubled solid state visible laser is pumped by the diode pump source and produces a pulsed laser output with a train of pulses. Resources provide instructions for the creation of the pulsed output, with on and off times that provide for substantial confinement of thermal effects at a target site. This laser system results in tissue specific photoactivation (or TSP) without photocoagulation damage to any of the adjacent tissues and without causing full thickness retinal damage and the associated vision loss.

The present invention is directed to detection and measurement of gene transcripts in blood. Specifically provided is a RT-PCR analysis performed on a drop of blood for detecting, diagnosing and monitoring diseases using tissue-specific primers. The present invention also describes methods by which delineation of the sequence and / or quantitation of the expression levels of disease-associated genes allows for an immediate and accurate diagnostic / prognostic test for disease or to assess the effect of a particular treatment regimen.