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.