Methods comprising apoptosis inhibitors for the generation of transgenic pigs

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Stem Cell Related Patent Number US6635740

Title:Ligand/lytic peptide compositions and methods of use
Inventors:Enright, Frederick M.; Baton Rouge, LA, USA
Jaynes, Jesse M.; Baton Rouge, LA, USA
Hansel, William; Baton Rouge, LA, USA
Koonce, Kenneth L.; Baton Rouge, LA, USA
McCann, Samuel M.; Baton Rouge, LA, USA
Yu, Wen H.; Baton Rouge, LA, USA
Melrose, Patricia A.; Baton Rouge, LA, USA
Foil, Lane D.; Baton Rouge, LA, USA
Elzer, Philip H.; Baton Rouge, LA, USA
Summary:This invention describes a novel fusion compound composed of hormone and lytic peptide, and methods of use in selective cell killing. The invention relates to amphipathic lytic peptides which are ideally suited for use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction, such as inducing sterility or long-term contraception, or in the attack of tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. Further disclosed are methods by which the in vivo administration of a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand, as the peptides are described as acting directly on cell membranes rather than requiring internalization. Means of administration are included for a combination of gonadotropin-releasing hormone (GnRH or a GnRH agonist) and a membrane-active lytic peptide, resulting in long-term contraception or sterilization in animals in vivo. Also described are genes encoding a lytic peptide or encoding a lytic peptide or peptide hormone fusion which may readily be inserted into hematopoietic stem cells or myeloid precursor cells. Applications in gene therapy are included, such as in the treatment of malignant or non-malignant tumors, and other diseases caused by clones or populations of normal host cells bearing specific receptors such as lymphocytes, and in the treatment of hormone-dependent cancer, viral infections and auto-immune diseases.
Abstract:Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components--the ligand and the lytic peptide--may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of normal host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.
US Patent Website:Click Here for Full Text of Patent
Title Number:US6635740
Application Number:US1999000381879
Date Filed:24/09/1999
Date Published:21/10/2003
Assignee:Board of Supervisors of Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA, USA


 
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