Use of a Truncated eIF-5A1 Polynucleotide to Induce Apoptosis in Cancer Cells
AssigneeSenesco Technologies, Inc.
InventorsJohn E. THOMPSON, Zhong SUN, Catherine TAYLOR, Richard DONDERO, Zhenyu CHENG
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Abstract
The present invention relates to the combinatorial use of an siRNA targeted against an endogenous gene to knock out or knock down expression of the endogenous gene in a host and a delivery of a polynucleotide encoding the gene in a delivery vehicle/expression vector to the host to provide expression in the host of the protein encoded by the polynucleotide. The present invention also relates to a truncated form of eIF-5A1 that is useful for inducing apoptosis and killing of cells, especially cancer cells in a mammal.
Claims57
A method for inducing apoptosis in a cancer cell or in a tumor in a subject, the method comprising administering an eIF5A1 polynucleotide that encodes a truncated eIF5A1 protein.
An isolated polynucleotide encoding a truncated eIF5A1 protein wherein the polynucleotide comprises the sequence set forth in SEQ ID NO:38.
An isolated polynucleotide encoding a truncated eIF5A1 protein wherein the truncated protein comprises the amino acid sequence set forth in SEQ ID NO:37.
An isolated truncated eIF5A1 polypeptide formed by caspase mediated cleavage of eIF5A1.
A method for inducing apoptosis in a cancer cell or in a tumor in a subject, the method comprising administering an eIF5A1 polynucleotide that encodes a truncated eIF5A1 protein in combination with a full length eIF5A1 polynucleotide.
A method of inducing apoptosis is a mammalian cancer cell or mammalian tumor, the method comprising administering to the mammal the composition of claim 42.
A composition comprising a complex of an eIF5A1 siRNA targeted against the 3′ end of eIF5A1, an expression vector comprising a polynucleotide encoding a mutant eIF5A1 wherein the mutant eIF5A1 is unable to be hypusinated, and wherein the siRNA and the expression vector are complexed to polyethylenimine to form a complex.
A composition comprising an siRNA targeted against a target gene to suppress endogenous expression of the target gene in a subject;
- and a polynucleotide encoding a target protein capable of being expressed in the subject in an RNAI resistant plasmid, wherein the siRNA and the plasmid are complexed to polyethylenimine to form a complex.
A composition comprising an eIF5A1 siRNA targeted against the 3′ end of eIF5A1 and an expression vector comprising a polynucleotide encoding a mutant eIF5A1 wherein the mutant eIF5A1 is unable to be hypusinated, and wherein the siRNA and the expression vector are delivered to a subject to treat cancer.
Dependencies are inferred from the claim text.