Selective killing of cells by activation of double-stranded rna dependent protein kniase-pkr

A method according to (2) wherein the DNA sequence is contained within any of a plasmid, a virus or a liposome or is delivered to the cell as naked DNA or is transcribed from an RNA sequence contained within a retrovirus

A method according to (2). wherein the DNA sequence is contained within a virus selected from the group consisting of an adenovirus, vaccinia virus and a herpes virus.

A method according to (3), wherein the DNA sequence is naked DNA, the naked being attached to a carrier.

A method according to (1). wherein obtaining an antisense RNA in step (b) further comprises:

• selecting an RNA sequence encoding anti-sense RNA wherein the RNA sequence is replicated in the target population to form double stranded RNA.

A method according to (6), wherein the RNA sequence is contained within a virus.

A method according to (7),wherein the virus is a lentivirus.

A method according to (6), wherein the RNA sequence includes a U6 small nuclear RNA promoter.

A method according to (1),wherein the target population of cells is selected from the group consisting of:

• neoplastic cells, autoimmune T-lymphocytes, infectious agents, smooth muscle cells in blood vessel plaque, cells in abnormal blood vessel growth, cells in psoriasis and keloid scarring.

A method according to (1),wherein the targeted population of cells are neoplastic cells.

A method according to (11),wherein the neoplastic cells are glioblastoma cells.

A method according to (11), wherein the neoplastic cells are lymphomas

A method according to (1), wherein the neoplastic cells are located in vivo in a subject

A method according to 1, wherein the neoplastic cells are located ex vivo in a culture vessel,

A method according to 1, wherein step (c) further comprises administering to the population of cells, an effective amount of interferon.

A method according to 1, wherein the anti-sense RNA has a sequence selected from SEQ 1-4 .

A method according to 1, wherein the double stranded RNA is at least 30 nucleotides in length.

A method according to 17, wherein the double stranded RNA is lee than 100 nucleotides in length.

A method according to 20, wherein the genetic locus is characterized by a mutation.

A method according to 20, where the proliferative disorder is neoplastic disease.

A method according to 20, wherein the proliferative disorder is psoriasis.

A method according to 20, wherein the proliferative disorder results from abnormal autoimmune T-lymphocytes.

A method according to 20, wherein the proliferative disorder includes vasculogenesis or angiogenesis

A pharmaceutical composition for treating proliferative disorders, comprising:

• an effective tumor cell growth inhibiting amount of anti-sense RNA, the antisense RNA having a sequence that is complementary to a contiguous mRNA sequence present in a neoplastic cell and absent in non-neoplastic cells, so as to form a double stranded RNA for activating a double stranded RNA dependent protein kinase and inhibiting tumor cell growth

A composition according to 26, wherein the anti-sense RNA has a sequence selected from the group consisting of SEQ ID Nos 1,3, 7, 9, 11, and 13 .

A composition according to 26, wherein the pharmaceutical composition. further comprises an interferon.

An anti-sense RNA, comprising:

• a natural or synthetic molecule having a length of less than 100 nucleotides, and having a sequence that hybridizes in situ or under stringent conditions in vitro with a contiguous nucleotide sequence that spans a site-specific mutation on a mammalian chromosome

An anti-sense mRNA according to 29, comprising:

• a sequence selected from the group consisting of SEQ ID Nos 1, 3, 5, 7, 9, 11 and 13.

A nucleic acid comprising:

• a sequence that is a template for an anti-sense RNA, wherein the anti-sense RNA hybridizing under stringent conditions to a messenger RNA, the messenger RNA being transcribed from a contiguous nucleotide sequence that spans a site specific mutation on a mammalian chromosome, the mutation occurring in a neoplastic cell and absent in a non-neoplastic cell, the nucleic acid having a length of less than 100 nucleotides

A vector comprising:

• a sequence that is a template for an anti-sense RNA of greater than 30 nucleotides and less than 100 nucleotides in length, wherein the anti-sense RNA hybridizes to an RNA, the RNA being identical to a transcription product from a contiguous nucleotide sequence that spans a site specific mutation on a mammalian chromosome, the mutation occurring in a neoplastic cell, being absent in a non-neoplastic cell at that site.

A vector according to 32, consisting of a retroviral vector

A vector according to 33 wherein the retroviral vector is a lentivirus

A cell population having transfected therein a vector according to 32

A cell population according to 35, wherein the transfection is a stable and the cell population is maintained in a cell culture medium,