Louisiana State University and Agricultural & Mechanical College

Transgenrx, Inc.

Proteovec Holding, L.l.c.

University of Georgia Research Foundation, Inc.

Richard K Cooper

William C Fioretti

Frederick M Enright

Gary G Cadd

Kenneth F De Boer

Ronald L Thune

Emmett B Shotts, Jr

The present invention provides novel compositions to transfect cells for production of growth hormone (GH). These novel compositions also are used to produce germline transgenic birds that can successfully pass the transgene encoding growth hormone to their offspring. These novel compositions include components of vectors such as a vector backbone, a novel promoter, and a gene of interest that encodes for GH, and the vectors comprising these components. In one embodiment these vectors are transposon-based vectors. The present invention also provides methods of making these compositions and methods of using these compositions for the production of GH in vitro and in vivo. In one embodiment the GH is human (h)GH.

Vectors for production of growth hormone

Novel compositions for the in vitro or in vivo production of specific proteins are provided. The compositions comprise components of vectors, such as a vector backbone, a promoter, and a gene of interest that encodes for the protein of interest, and the transposon-based vectors comprising these components. Also provided are methods of making these compositions and methods of using these compositions for the production of desired proteins in vivo or in transfected cells in vitro.

Production of proteins using transposon-based vectors

Novel compositions for the production of the light and heavy chains of an antibody are provided. These novel compositions are also used to produce germline transgenic birds that can successfully pass the transgene encoding the antibody to their offspring. The compositions comprise components of vectors, such as a vector backbone, a promoter, and a gene of interest that encodes the light or heavy chain of an antibody, and the vectors comprising these components. In certain embodiments, these vectors are transposon-based vectors. Also provided are methods of making these compositions and methods of using these compositions for the production of the light and heavy chains of an antibody. In one embodiment, the antibody is a human monoclonal antibody.

Vectors for production of antibodies

Methods and compositions for the administration of transposon-based vectors to the reproductive organs of animals and the creation of transgenic animals. Preferred methods involve administration of the transposon-based vectors to the lumen of the oviduct of an avian, expression of a vector derived transgene in the avian, and deposition of the resultant polypeptide in an egg. This invention allows for large amounts of protein to be deposited in the egg.

Administration of transposon-based vectors to reproductive organs

Methods and compositions are presented for the administration of transposon-based vectors to an animal or human to provide gene therapy to the animal or human.

Gene therapy using transposon-based vectors

Methods and compositions are presented for the administration of transposon based vectors to an animal or human to provide gene therapy to the animal or human.

Administration of modified transposon-based vectors has been used to achieve stable incorporation of exogenous genes into animals. These transgenic animals produce transgenic progeny. Further, these transgenic animals produce large quantities of desired molecules encoded by the transgene. Transgenic egg-laying animals produce large quantities of desired molecules encoded by the transgene and deposit these molecules in the egg.

Gene regulation in transgenic animals using a transposon-based vector

Novel means have been discovered for increasing the resistance of an animal host (including humans) to diseases caused by intracellular bacteria, protozoa, and viruses. The infection treated may, for example, be equine infectious anemia, or infection by the human immunodeficiency virus. Novel means have also been found for treating tumors. Augmentation of the host's defenses against infectious diseases or tumors is achieved by 'arming' the host's cells with an exogenous gene encoding a natural or synthetic lytic peptide. For example, the transfection of hematopoietic stem cells and embryonic cells will produce animals with enhanced disease resistance; and transfection of TIL (tumor infiltrating lymphocytes) cells or other cells can be used in the treatment of tumors. Genes coding for a cecropin or other native or synthetic lytic peptide can be transferred and stably expressed in mammalian, bony fish, other vertebrate, and other animal cells. The transformed cells have the ability to produce and secrete a broad spectrum chemotherapeutic agent that has a systemic effect on certain pathogens, particularly pathogens that might otherwise evade or overcome host defenses. Novel means have also been discovered for transforming a eukaryotic cell with a gene under the control of an exogenous promoter that is responsive to an inducer of an acute-phase peptide or protein. For example, a moth promoter for the cecropin B gene has been found to function appropriately in a mammalian cell.

Transformed eukaryotic cells

Live-attenuated vaccines against Edwardsiella ictaluri or against Pasteurella piscicida are disclosed. Both vaccines are incapable of reversion to virulence, because both are made by deletion mutations in the aroA gene, the purA gene, or both. These vaccines may be used not only to vaccinate fish against Edwardsiella ictaluri or Pasteurella piscicida, but also to serve as vectors to present antigens from other pathogens to the fish, thereby serving as vaccines against other pathogens as well, with no risk of infection by reversion to the virulent form of the pathogen in which the antigen occurs naturally.

Attenuated, invasive vaccines against fish pathogens

Novel means have been discovered for increasing the resistance of an animal host (including humans) to diseases caused by intracellular bacteria, protozoa, and viruses. The infection treated may, for example, be equine infectious anemia, or infection by the human immunodeficiency virus. Novel means have also been found for treating tumors Augmentation of the host's defenses against infectious diseases or tumors is achieved by 'arming' the host's cells with an exogenous gene encoding a natural or synthetic lytic peptide. For example, the transfection of hematopoietic stem cells and embryonic cells will produce animals with enhanced disease resistance; and transfection of TIL (tumor infiltrating lymphocytes) cells or other cells can be used in the treatment of tumors. Genes coding for a cecropin or other native or synthetic lytic peptide can be transferred and stably expressed in mammalian, bony fish, other vertebrate, and other animal cells. The transformed cells have the ability to produce and secrete a broad spectrum chemotherapeutic agent that has a systemic effect on certain pathogens, particularly pathogens that might otherwise evade or overcome host defenses.

Transgenic fish capable of expressing exogenous lytic peptides

A novel transposen-based vector has been developed that enhances the integration of DNA into a host genome, particularly a eukaryotic genome. The novel vector has been used, for example, in the transformation of mammalian and fish cells with a gene coding for the inductive expression of the lytic peptide cecropin B, and in the production of transgenic fish containing a gene coding for the inductive expression of the lytic peptide cecropin B. This vector shows greater transformation efficiencies than do other means for transforming a gene into a eukaryotic chromosome. The novel vector allows the rapid and efficient transformation of a eukaryotic genome. Its use does not require the high level of skill needed for microinjections. Nor does it rely on homologous recombination events for a successful transformation, as do the prior methods of microinjection, electropotation, and lipofection. A novel modification of mini-transposons was made to adapt them to carry a gene of interest into a genome.

Transposon-based transformation vectors

Novel means have been discovered for increasing the resistance of a mammalian host (including humans) to diseases caused by intracellular bacteria, protozoa, and viruses. Novel means have also been found for treating tumors. Augmentation of the host's defenses against infectious diseases or tumors is achieved by 'arming' the host's cells with a gene encoding the lytic peptide cecropin B. The host's own leukocytes, other cells involved in resistance to infection, or other cells are transformed, and expression of the gene is induced when needed to combat pathogens. Transfection of hematopoietic stem cells with the cecropin B gene will enhance disease resistance in mammals; and transfection of TIL (tumor infiltrating lymphocytes) cells or other cells can be used in the treatment of tumors. The transformed cells have the ability to produce and secrete a broad spectrum chemotherapeutic agent which has a systemic effect on certain pathogens, particularly pathogens that might otherwise evade or overcome host defenses. The peptide's expression is preferably induced only in areas of infection, where it will most effectively augment the host's defense systems. Expression of the exogenous gene does not damage a healthy recipient cell.

Transformed mammalian cells capable of expressing cecropin b

The present invention provides a chondroitinase attenuated Edwardsiella ictaluri bacteria. Further, this invention provides a vaccine comprising a protective amount of a chondroitinase attenuated strain of Edwardsiella ictduri bacteria and a method for protecting a fish from Enteric Septicemia comprising administering the vaccine to the fish.

Growing community of inventors

Baton Rouge, LA, United States of America

Richard K Cooper