Abstract: A variety of zinc finger proteins (ZFPs) and methods utilizing such proteins are provided for use in treating neuropathic pain. ZFPs that bind to a target site in genes that are aberrantly expressed in subjects having neuropathic pain are described. In addition, ZFPs that bind to a target site in genes expressed at normal levels in subjects experiencing neuropathic pain, modulation of whose expression results in decreased pain perception, are also provided. For example, genes that are over-expressed in the dorsal root ganglia (DRG) of pain patients (e.g., VR1, TRKA and/or Nav1.8) can be repressed, whereas genes that are under-expressed in the same populations can be activated.

Abstract: The present invention provides transgenic, non-human animals that include a transgene that encodes a fatty acid desaturase, e.g., stearoyl-CoA desaturase, and methods for producing such animals. The invention further provides an expression cassette that includes a coding region for a desaturase such as stearoyl-CoA desaturase, operably linked to a heterologous, tissue-specific animal cell promoter. The invention further provides methods of producing a food product, such as milk, meat, or eggs, using a subject transgenic non-human animal, as well as food products harvested from a subject transgenic non-human animal.

Abstract: The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of the delivered gene and for in vivo secretion of the therapeutic protein from transduced muscle cells such that systemic delivery is achieved.

Abstract: Nucleic acid, including DNA, immunization is used to generate a protective immune response in a host, including humans, to a serine-threonine kinase (STK) of a strain of Chlamydia. A non-replicating vector, including a plasmid vector, contains a nucleotide sequence encoding a STK or a fragment of the STK that generates antibodies that specifically react with STK and a promoter sequence operatively coupled to the first nucleotide sequence for expression of the STK in the host. The non-replicating vector may be formulated with a pharmaceutically-acceptable carrier for in vivo administration to the host.

Abstract: A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

Abstract: The present invention provides a herpes virus with improved oncolytic properties which comprises a gene encoding an immunomodulatory cytokine and which lacks a functional ICP34.5 gene and a functional ICP47 encoding gene.

Abstract: Dendritic cells play a critical role in antigen-specific immune responses. Materials and methods are provided for treating disease states, including cancer and autoimmune disease, by facilitating or inhibiting the migration or activation of antigen-presenting dendritic cells. In particular, chemokines are used to initiate, amplify or modulate an immune response. In one embodiment, chemokines are used to attract dentritic cells to the site of antigen delivery. An increase number of dendritic at the site of antigen delivery means more antigen uptake and a modified immune response.

Abstract: The invention is directed to tissue-engineered biografts, methods for preparing the biografts of the invention, and methods for repairing a damaged myocardium in a mammal. The methods of the invention can include providing a three-dimensional porous polysaccharide matrix; introducing mammalian cells into said matrix; growing said cells in said matrix in vitro, until a tissue-engineered biograft is formed; and transplanting the tissue-engineered biograft onto myocardial tissue or myocardial scar tissue of said mammal. The tissue-engineered biograft of the invention can form a contracting tissue. The methods of the invention can optionally include removing scar tissue or dead tissue from the site of implantation prior to transplanting the biograft.

Abstract: The present invention relates to a Type II diabetes model mouse, having a causative gene responsible for the following characteristics (1) to (3) in the heterologous or homologous state, wherein the characteristics are autosomal recessive genetic traits: (1) having a higher blood sugar level as compared to a normal strain mouse at 10 to 14 weeks of age and having a blood glycosylated hemoglobin concentration of 2.5% or higher at 10 to 14 weeks of age or older; (2) being positive in test for urine sugar at 10 to 14 weeks of age; and (3) exhibiting essentially no inflammation of the pancreatic islets and having a blood insulin concentration equivalent to or higher than that of a normal strain mouse. According to the present invention, there is provided a novel mouse having a gene responsible for the spontaneous development of type II diabetes.

Abstract: Disclosed herein are isolated nucleic acid molecules encoding a humanized version of a calcitonin gene-related peptide (CGRP) receptor, which comprises the G-protein coupled receptor calcitonin-receptor-like receptor (CRLR) and the receptor-activity-modifying protein 1 (RAMP1). The humanized CGRP receptors of the present invention attain pharmacological profiles similar to the wild type human receptor via modifications to the respective mammalian RAMP1 nucleotide sequence, specifically at amino acid 74. Also described are related recombinant vectors, recombinant hosts and associated methods for generating such humanized CGRP receptors. Also presented are non-human transgenic animals which express humanized RAMP1. Such animals have been engineered to provide for a CGRP pharmacological profile similar to human CGRP.

Abstract: A transgenic mouse whose genome comprises a transcriptional control region operably linked to a cDNA encoding calreticulin (CRT) is described.

Abstract: Disclosed are compositions comprising a novel cell-death protecting protein, sentrin-1, and the gene which encodes it. Also disclosed are methods of making and using sentrin polypeptides and nucleic acid segments in various diagnostic and pharmaceutical applications. In a preferred embodiment, overexpression of sentrin-1 confers protection against both anti-Fas/APO-1 and TNF-induced apoptosis.

Abstract: It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an ?-galactosyl (Gal) epitope, for example, Gal?(1->3)Gal?(1->4)GlcNac (linear B type 2) or Gal?(1->3) Gal?(1->4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans.

Abstract: The invention provides methods for determining a prognosis for survival for a cancer patient. One method involves (a) measuring a level of a TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) comparing the level of TUCAN in the sample to a reference level of TUCAN, wherein a low level of TUCAN in the sample correlates with increased survival of the patient. Another method involves (a) measuring a level of TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) classifying the patient as belonging to either a first or second group of patients, wherein the first group of patients having low levels of TUCAN is classified as having an increased likelihood of survival compared to the second group of patients having high levels of TUCAN.

Abstract: A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.

Abstract: A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and/or increase in one or more tryptophan metabolites within the local macrophage microenvironment Studies demonstrate that expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and therefore other types of transplantation, and that inhibitors of IDO can be used to activate T cells and therefore enhance T cell activation when the T cells are suppressed by pregnancy, malignancy or a virus such as HIV. Inhibiting tryptophan degradation (and thereby increasing tryptophan concentration while decreasing tryptophan metabolite concentration), or supplementing tryptophan concentration, can therefore be used in addition to, or in place of, inhibitors of IDO.

Abstract: The present invention relates to transgenic animal models for altered Wnt expression. The present invention also provides methods for generating animal models and screening methods for identifying biologically active compounds.

Abstract: The present invention relates generally to the field of generating genetically modified C57 mice. More particularly, the present invention pertains to 1) blastocyst-derived mouse embryonic stem cell (ES) cell lines including, but not limited to, the IC1, IC2, IAC1, IAC2, IAC3, IAC4, IAC5, IAC6, IAC7 or IAC8 ES cell line, 2) to efficient methods of making genetically modified C57 mice by introducing the modified C57 ES cells into the mouse blastocysts of either the same mouse strain and/or color of albino C57 strain, or other C57 strain, to generate genetically modified novel, useful and hereto unknown models of C57 mice, and to methods for identifying the chimerism of chimeras which can be not known by coat color.

Abstract: This invention provides a series of low-copy number plasmids comprising restriction endonuclease recognition sites useful for cloning at least three different genes or operons, each flanked by a terminator sequence, the plasmids containing variants of glucose isomerase promoters for varying levels of protein expression. The materials and methods are useful for genetic engineering in microorganisms, especially where multiple genetic insertions are sought.

Abstract: This invention provides novel methods of obtaining autologous monoclonal antibodies (AMABs) to self-antigens or homologs thereof. The method involves obtaining a genetically engineered host animal that does not biosynthesize at least one epitope of the antigen and utilizes the lack of self-tolerance of the host to the epitope to produce antibodies specific to the antigen. The invention also encompasses the AMABs produced by the methods. The invention further encompasses methods of isolating cells comprising the use of such AMABs that have specificity for a cell surface antigen.