Abstract: Disclosed herein are methods of obtaining human hematopoietic cells from human pluripotent embryonic stem cells using mammalian stromal cells. Hematopoietic cells derived in this way are useful for creating cell cultures suitable for transplantation, transfusion, and other purposes.

Abstract: Disclosed are methods for the isolation of primordial germ cells, culturing these cells to produce primordial germ cell-derived cell lines, methods for transforming both the primordial germ cells and the cultured cell lines, and using these transformed cells and cell lines to generate transgenic animals. The efficiency at which transgenic animals are generated by the present invention is greatly increased, thereby allowing the use of homologous recombination in producing transgenic non-rodent animal species.

Abstract: Glaucoma compositions comprising the GLC1A gene are disclosed.

Abstract: Disclosed herein is a transgenic non-human animal carrying a transgene which expresses non-infectious HIV ribonucleic acid and complementary proteins thereof. Among the expressed proteins, which can be found in the milk, serum and several tissues, are the gag and envelope proteins. The transgenic animal is useful as a source for obtaining the complementary proteins, and as an animal model to study HIV host cell interactions and to evaluate anti-HIV drugs.

Abstract: A process for screening an agent to determine its effect upon the frequency of genome rearrangement in transgenic mammals. The process comprises the steps of: (a) providing a transgenic mammal into which repeated genetic elements have been inserted into its haploid genome. The repeated genetic elements are sufficiently homologous so that, under ambient conditions, they recombine with each other and give rise to an identifiable genome rearrangement at a rate of at least about 1×10−11 occurrences per cell per generation. In a preferred embodiment the rearrangement can be identified as a phenotypic event or by PCR. The process further comprises (b) exposing at least one of the transgenic mammals to the agent to be tested, thereby providing an exposed mammal and (c) determining the extent of genome rearrangement which exists in a first exposed animal selected from the group consisting of the exposed mammal, its offspring, and mixtures thereof.

Abstract: Nucleic acid constructs comprising hypoxia response elements in operable linkage with a coding sequence of a gene of interest, and methods for expressing a nucleic acid sequence using the constructs, are disclosed. In particular, such nucleic acid constructs comprise genes encoding prodrug activation systems or cytokines.

Abstract: The invention provides an isolated DNA which regulates vascular smooth muscle cell-specific transcription of a polypeptide-encoding sequence to which it is operably linked

Abstract: The present invention provides a method for inducing reendothelialization of the lining of an injured blood vessel comprising contacting the injured portion of the vessel with nucleic acid encoding an endothelial cell mitogen operably linked to a promoter (nucleic acid cassette) to result in expression of the mitogen when delivered to the cells at the site of vascular injury. The resulting reendothelialization of the injured blood vessel inhibits smooth muscle cell proliferation and consequently reduces restenosis. The methods of the present invention may be used to treat any blood vessel injury that results in denuding of the endothelial lining of the vessel wall, including, for example, those injuries resulting from balloon angioplasty and deployment of endovascular stents.

Abstract: This invention pertains to a method for homing hematopoietic stem cells to bone marrow stromal cells in a host. The method comprises, administering to the host genetically-engineered hematopoietic stem cells capable of expressing a first member of a ligand-receptor binding pair. The stem cells are administered to the host under conditions whereby binding of the first member of the ligand-receptor binding pair to the second member of the ligand-receptor binding pair, present on stromal cells, occurs thereby homing the stem cells to the stromal cells. This method is useful for transplanting bone marrow in a host or in treating a host afflicted with a disease associated with a disorder of the bone marrow.

Abstract: The invention relates to methods for targeting an exogenous polynucleotide or exogenous complementary polynucleotide pair to a predetermined endogenous DNA target sequence in a eukaryotic cell by homologous pairing, particularly for altering an endogenous DNA sequence, such as a chromosomal DNA sequence, typically by targeted homologous recombination. In certain embodiments, the invention relates to methods for targeting an exogenous polynucleotide having a linked chemical substituent to a predetermined endogenous DNA sequence in a metabolically active eukaryotic cell, generating a DNA sequence-specific targeting of one or more chemical substituents in an intact nucleus of a metabolically active eukaryotic cell, generally for purposes of altering a predetermined endogenous DNA sequence in the cell.

Abstract: The present invention relates to recombinatorial substrates which include a promoter, a terminator, a gene positioned 3′ to the terminator and whose expression is to be controlled, and recombination sites on each side of the terminator such that when the substrate is treated with a specific recombinase the gene will be expressed. Recombinatorial substrates which have a promoter, a gene to be controlled, and recombination sites on each side of the gene which when treated with recombinase delete the gene are also provided. Also enclosed are methods of creating transgenic mammals carrying the recombinatorial substrate and methods for activating the recombinatorial substrate.

Abstract: A method of reducing immune response to a viral vector containing a selected transgene is provided. The method involves co-administration of the viral vector and a selected immune modulator capable of inhibiting the formation of neutralizing antibodies and/or CTL elimination of the vectors upon repeated administration.

Abstract: The invention provides methods and compositions for expressing targeted gene products in vertebrate neurons. The compositions include gene trap vectors comprising a polynucleotide comprising promoterless selectable marker and axon reporter encoding sequences, which may be operatively joined to an internal ribosome-entry site, and may comprise a splice acceptor site located 5′ to the selectable marker and axon reporter encoding sequences. The methods include methods of expressing an axon reporter in a cell by transferring the subject vectors into an embryonic stem cell and incubating the cell under conditions whereby the cell or a progeny of the cell differentiates into a neuron comprising an axon or dendrites, and the neuron expresses the axon reporter under the transcriptional control of the gene; and specifically detecting the axon reporter in the axon or dendrites. Neuronal specific expression may also be effected in disclosed binary systems.

Abstract: The present application shows that the expression of Coxsackievirus and/or Adenovirus (CAR) in various lymphocyte cell lines is sufficient to facilitate the efficient transduction of these cells by adenoviruses. This property of CAR does not require its cytoplasmic domain. Use of a truncated CAR (tCAR) lacking the cytoplasmic domain has the unexpected advantage in that integrin expression is not increased in lymphocytes expressing tCAR, whereas lymphocytes expressing full-length CAR exhibit upregulated integrin expression. Further provided are transgenic mice which have been genetically engineered for tissue-specific (lymphocyte) expression of tCAR.

Abstract: The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in utility for agents such as oligonucleotides which are plagued with problems in reaching targeted sites in necessary therapeutic levels. The delivery system includes gas-filled microbubbles formed in a nitrogen-free environment. Microbubbles formed through sonication in a nitrogen-free environment are smaller and more stable than microbubbles sonicated in the presence of room air.

Abstract: A method for determining the Rfp-Y or B-F haplotype of a chicken which involves a nucleic acid amplification-single-stranded conformational polymorphism (“SSCP”) method is disclosed.

Abstract: The invention provides a transgenic mouse that is a model for heart muscle disease and heart failure. Also provided are methods of using the transgenic mouse model to study heart muscle disease and heart failure and conditions and treatments related thereto.

Abstract: The present invention relates to new viral vectors derived from adenoviruses, their preparation and utilization in gene therapy. It relates particularly to defective recombinant adenoviruses wherein the Iva2 gene at least is inactivated.

Abstract: The susceptibility to human immunodeficiency virus (HIV) infection depends on the cell surface expression of the human CD4 molecule and a human fusion accessory factor associated with HIV infection (CXCR4). CXCR4 is a member of the 7-transmembrane segment superfamily of G-protein-coupled cell surface molecules. CXCR4 plays an essential role in the membrane fusion step of HIV infection. The establishment of stable cell lines that coexpress human CD4 and CXCR4 provides valuable tools for the continuing research of HIV infection and the development of more effective anti-HIV therapeutics.

Abstract: Primordial germ cells are extracted from post blastocyst piorcine embryos such as extracting primordial germ cells from the gonadal ridges of 25-day porcine embryos. The primordial germ cells are cultured in long term culture (over 30 days) resulting in cells which resemble embryonic stem cells in morphology and with respect to maintaining pluripotency. The cells obtained can be maintained for several months in culture and can be genetically manipulated using homologous recombination technology in order to insert desired genetic material into the genetic complement of the cell at a desired location. The genetically manipulated cell can be inserted into a porcine blastocyst to produce a chimeric porcine.