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AssigneeBoard of Supervisors of Louisiana State University and Agricultural and Mechanical College
InventorsFrederick M. Enright, Jesse M. Jaynes, William Hansel, Kenneth L. Koonce, Samuel M. McCann, Wen H. Yu, Patricia A. Melrose, Lane D. Foil, Philip H. Elzer
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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.
A compound comprising a first domain and a second domain, wherein:
A method for killing or inhibiting the growth of a cell in a mammal, wherein the activity of the cell is dependent on the binding of a receptor on the cell surface to a ligand, said method comprising administering to the mammal an effective amount of the ligand on which the activity of the cell depends, and an effective amount of a lytic peptide, wherein the lytic peptide comprises from 10 to 39 amino acid residues, is basic, and will form an amphipathic alpha helix.
A method for decreasing fertility in an animal, comprising administering to the animal an effective amount of a compound comprising a first domain and a second domain;
A method for selectively reducing the number of viable gonadotrophic cells in the pituitary of an animal, comprising the consecutive steps of:
A method for selectively reducing the number of viable gonadotrophic cells in the pituitary of an animal, comprising administering to the animal an effective amount of a compound comprising a first domain and a second domain;
A method for selectively reducing the number of viable neurons having gonadotrophic receptors in an animal, comprising the consecutive steps of:
A method for selectively reducing the number of viable neurons having gonadotrophic receptors in an animal, comprising administering to the animal an effective amount of a compound comprising a first domain and a second domain;
A method for decreasing fertility in an animal, comprising the consecutive steps of:
A method as recited in herein the hormone and the lytic peptide are expressed by an exogenous gene or genes in a plant consumed by the insect.
A plant containing a first exogenous gene that encodes gonadotropin-releasing hormone or that encodes lamprey III luteinizing hormone releasing hormone (1-LHRH-III) or that encodes an analog of one of these hormones;
A plant containing an exogenous gene that encodes a peptide comprising a first domain and a second domain;
A method for killing or inhibiting the growth of a cell in a hormone-dependent or ligand-dependent tumor in a mammal, comprising administering to the mammal an effective amount of the hormone or ligand on which the growth of the tumor depends, and an effective amount of a lytic peptide, wherein the lytic peptide comprises from 10 to 39 amino acid residues, is basic, and will form an amphipathic alpha helix.
Dependencies are inferred from the claim text.