Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germ-line transgenic animals by direct injection of nucleic acid molecules into animals.

Abstract: This invention provides novel methods and compositions for treating and preventing seizures by administration of ASIC1a receptor activating compounds. A novel method of assaying ASIC1a receptor activating compounds is included in the present invention. According to the invention applicants have demonstrated that seizure duration, intensity, and progression may be modulated by administration of an ASIC1a receptor activator which acts to increase the endogenous activity of ASIC1a receptors to mediate the effects of low pH in the CNS. The inventors have also found that the ASIC1a receptor activator may prevent such seizures altogether.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of making and using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: The invention provides a transgenic Mustelidae in which a gene associated with a human disease or condition comprises a targeted genetic modification, and uses thereof. Also provided is a method to cryopreserve Mustelidae embryos or cells, and to enhance the number of live offspring from cryopreserved Mustelidae embryos.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: The present invention offers new therapies for treating Cystic Fibrosis (CF), that are based on novel DNA molecules and proteins encoded by the DNA molecules. The present invention features DNA molecules encoding CFTR having a partially deleted R domain. The partial deletions in the R domain are between residues 708 and 835 of the wild-type CFTR.

Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: The invention presented herein provides methods and compositions for the prevention and treatment of bacterial infections. The methods are based on the discovery that depletion of bioavailable iron stimulates surface motility in bacteria thus inhibiting the ability of a bacterial population to develop into a biofilm.

Abstract: The present invention relates to nucleic acid molecules comprising certain truncated forms of the human cytomegalovirus (CMV) immediate-early enhancer-promoter, either alone or operably linked to transgenes of interest, including those encoding partially-deleted CFTR proteins. This invention further relates to vectors comprising these nucleic acid molecules and host cells transformed by such vectors. The nucleic acid molecules, vectors and transformed host cells of the present invention are useful for treating a variety of genetic, metabolic and acquired diseases, including inter alia cystic fibrosis (CF) airway disease.

Abstract: The present invention offers new therapies for treating Cystic Fibrosis (CF), that are based on novel DNA molecules and proteins encoded by the DNA molecules. The present invention features DNA molecules encoding CFTR having a partially deleted R domain. The partial deletions in the R domain are between residues 708 and 835 of the wild-type CFTR.

Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13–19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: A method for killing infectious microbial cells by exposing the microbial cells to endogenous antimicrobial compounds. Activation of the antimicrobials is achieved by addition of low permeability, non-ionic osmolytes to lower ionic strength in body fluids where the antimicrobials have been previously suppressed by alteration of ionic transport (increase in salt concentration). The method can be used to treat cystic fibrosis. Cystic fibrosis causes elevated salt concentrations in the airway surface liquid (ASL) occur due to the impaired chloride transport across the epithelia. Xylitol has been found to be an effective low permeability, non-ionic osmolyte for use in the present invention.

Abstract: An assay for determining agonists, antagonists, or modulators for acid-sensing ion channels. The assay is especially useful for screening analgesics. The screening assay can be provided in a kit form. The assay comprises administering the composition to be screened to cells expressing acid-gated channels and then determining whether the composition inhibits, enhances, or has no effect on the channels when acid is introduced. The determination can be performed by analyzing whether a current is sustained by the cells in the presence of the composition and the acid. This current can be compared to that sustained by the FMRFamide and related peptides.

Abstract: A method for killing infectious microbial cells by exposing the microbial cells to endogenous antimicrobial compounds. Activation of the antimicrobials is achieved by addition of low permeability, non-ionic osmolytes to lower ionic strength in body fluids where the antimicrobials have been previously suppressed by alteration of ionic transport (increase in salt concentration). The method can be used to treat cystic fibrosis. Cystic fibrosis causes elevated salt concentrations in the airway surface liquid (ASL) occur due to the impaired chloride transport across the epithelia. Xylitol has been found to be an effective low permeability, non-ionic osmolyte for use in the present invention.

Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: The present invention offers new therapies for treating Cystic Fibrosis (CF), that are based on novel DNA molecules and proteins encoded by the DNA molecules. The present invention features DNA molecules encoding CFTR having a partially deleted R domain. The partial deletions in the R domain are between residues 708 and 835 of the wild-type CFTR.

Abstract: The present invention relates to the targeted delivery of a delivery vehicle construct which specifically binds to and stimulates endocytosis into cells expressing the urokinase plasminogen activator receptor (uPAR), and particularly human airway epithelia. The delivery vehicle construct comprises a portion of uPA and a cargo linked thereto and is useful for the targeted delivery of the cargo to a cell. In one aspect of the invention, the uPA portion of the delivery vehicle construct comprises the wild-type uPA, a fragment of uPA which has the PAI-1 binding region deleted, or a uPA peptide comprising amino acids 13-19 and is useful for the targeted delivery of the cargo to cells, and in particular to airway epithelia. The present invention also provides a method for delivering the delivery vehicle construct to a cell.

Abstract: An assay for determining agonists, antagonists, or modulators for acid-sensing ion channels. The assay is especially useful for screening analgesics. The screening assay can be provided in a kit form. The assay comprises administering the composition to be screened to cells expressing acid-gated channels and then determining whether the composition inhibits, enhances, or has no effect on the channels when acid is introduced. The determination can be performed by analyzing whether a current is sustained by the cells in the presence of the composition and the acid. This current can be compared to that sustained by the FMRFamide and related peptides.

Abstract: Novel compositions for modulating acid-sensing ion channels (ASIC) function comprising ASIC&agr;, ASIC&bgr;, and BNC1 and derivatives thereof; methods for modulating ASIC function and methods for treating cognitive disorders and for memory enhancement using the novel compositions of the invention; and a method for increasing synaptic plasticity are described.