Abstract: Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Abstract: Novel polypeptides are provided, together with methods for making and using them, and nucleic acids encoding them. These polypeptides are useful as cell surface adhesion molecules and ligands, and are useful in therapeutic or diagnostic compositions and methods.

Abstract: This invention provides a method for determining susceptibility for an HCV or HCMV anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c).

Abstract: Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Abstract: This invention provides a method for determining susceptibility for an anti-viral drug comprising: (a) introducing a resistance test vector comprising a patient-derived segment and an indicator gene into a host cell; (b) culturing the host cell from (a); (c) measuring expression of the indicator gene in a target host cell; and (d) comparing the expression of the indicator gene from (c) with the expression of the indicator gene measured when steps (a)-(c) are carried out in the absence of the anti-viral drug, wherein a test concentration of the anti-viral drug is present at steps (a)-(c); at steps (b)-(c); or at step (c) This invention also provides a method for determining anti-viral drug resistance in a patient comprising: (a) determining anti-viral drug susceptibility in the patient at a first time using the susceptibility test described above, wherein the patient-derived segment is obtained from the patient at about said time;(b) determining anti-viral drug susceptibility of the same patient at a later tim

Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, the .beta..sub.2- microglobulin gene is inactivated for reducing or eliminating the expression of functional Class I MHC antigens. The resulting cells may be used as allogeneic donor cells. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.

Abstract: Novel derivatives of cell surface proteins which are homologous to the immunoglobulin superfamily (adhesons) are provided. Amino acid sequence variations are introduced into adheson, the most noteworthy of which are those in which the transmembrane and, preferably, cytoplasmic domains are rendered functionally inactive, and in which adheson extracellular domains replace an immunoglobulin variable region. These variants are useful in therapy or diagnostics, in particular, CD4 variants are therapeutically useful in the treatment of HIV infections.

Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: Novel multispecific chimeric receptor DNA sequences, expression cassettes and vectors containing these sequences as well as cells containing the chimeric DNA and novel chimeric receptor proteins expressed from the sequences are provided in the present invention. The novel multispecific chimeric receptor DNA and amino acid sequences comprise at least three domains that do not naturally exist together: (1) a multispecific binding domain comprising at least two extracellular inducer-responsive clustering domains which serves to bind at least one specific inducer molecule, (2) a transmembrane domain, which crosses the plasma membrane, and (3) either a proliferation signaling domain that signals the cell to divide, or an effector function signaling domain which directs a host cell to perform its specialized function.

Abstract: The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide.

Abstract: Antibodies with fully human variable regions against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Abstract: Diagnostic product and vaccine for Acquired Immuno-deficiency Syndrome (AIDS) and methods for making and using same, wherein viral polypeptide sequences from an AIDS associated retrovirus are expressed directly or as a fusion polypeptide in a prokaryotic or mammalian cell expression host to produce a diagnostic product which specifically binds complementary antibody produced by individuals afflicted with AIDS or a vaccine against AIDS which confers resistance to infection by AIDS associated retrovirus. The reverse transcriptase of an AIDS associated retrovirus is used separately or in a whole cell assay to identify compounds which selectively inhibit retroviral reverse transcriptase.

Abstract: The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide.

Abstract: Distinct .alpha.-, .beta.- and .gamma.-interferon genes from various animal species have been identified, cloned and expressed to produce the corresponding non-human animal interferon proteins. Specifically disclosed are interferons of bovine, porcine, feline and rabbit origin.

Abstract: Distinct .alpha.-, .beta.- and .gamma.-interferon genes from various animal species have been identified, cloned and expressed to produce the corresponding non-human animal interferon proteins. Specifically disclosed are interferons of bovine, porcine, feline and rabbit origin.

Abstract: The present invention is directed to novel chimeric proliferation receptor proteins and DNA sequences encoding these proteins where the chimeric proteins are characterized in three general categories. In one category, the novel chimeric proteins comprise at least three domains, namely, an extracellular inducer-responsive clustering domain capable of binding an extracellular inducer that transmits a signal to a proliferation signaling domain, a transmembrane domain and a proliferation signaling domain that signals a host cell to divide. In the second category, the novel chimeric proteins comprise at least two domains, namely, an intracellular inducer-responsive clustering domain capable of binding an intracellular inducer and a proliferation signaling domain that signals the cell to divide.

Abstract: Novel polypeptides are provided, together with methods for making and using them, and nucleic acids encoding them. These polypeptides are useful as cell surface adhesion molecules and ligands, and are useful in therapeutic or diagnostic compositions and methods.

Abstract: A recombinant DNA vector is provided that expresses exons of genomic DNA fragments that are inserted into the vector. The vector contains a promoter and a genomic DNA fragment so characterized and configured that the vector, upon transcription in a transfected eukaryotic cell culture, expresses the corresponding RNA segment of the genomic DNA fragment free of any intron.