CMV GENE PRODUCTS PROMOTE CANCER STEM CELL GROWTH
The disclosure relates generally to compositions and methods useful for inhibiting the infection and propagation of viral particles, particularly members of the Herpesviridae family, and more particularly to cytomegalovirus (CMV) and methods of treating diseases and disorders, including cell proliferative disorders, associated with CMV infection.
1 . A method of treating glioblastoma in a subject comprising administering to a glioblastoma stem cell an inhibitor of a IE1, US28 and/or pp71 from a herpes virus, wherein the inhibitor inhibits the expression or activity of the IE1, US28 and/or pp71 gene or polypeptide and inhibits glioblastoma stem cell self-renewal in the subject.
2 - 4 . (canceled)
5 . The method of claim 1 , wherein the herpes virus is selected from the group consisting of CMV, EBV, HHV-6A, HHV-6B and HHV-7.
6 . The method of claim 1 , wherein the glioblastoma is glioblastoma multiforme.
7 . The method of claim 1 , wherein the inhibitor of the IE1, US28 and/or pp71 or homolog is an inhibitory nucleic acid.
8 . The method of claim 7 , wherein the inhibitory nucleic acid is an siRNA, ribozyme or triplex molecule.
9 . The method of claim 1 , wherein the inhibitor of the IE1, US28 and/or pp71 or homolog is an inhibitory peptide.
10 . The method of claim 9 , wherein the inhibitory peptide binds to IE1, US28 or pp71 polypeptide and inhibits activity of IE1, US28 or pp71.
11 . The method of claim 8 , wherein the inhibitory nucleic acid has a sequence selected from the group consisting of SEQ ID NO:4, 5, 6, 7 and any combination thereof.
12 . A method of treating a cancer comprising exposing a cancer stem cell infected with CMV to at least one small inhibitory RNA molecule (siRNA) that targets a IE1 CMV gene, under conditions that permit induction of ribonucleic acid interference (RNAi), such that cancer stem cell renewal is inhibited.
13 - 14 . (canceled)
15 . The method of claim 12 , wherein the siRNA is a double stranded RNA (dsRNA) molecule, each strand of which is about 18-29 nucleotides long.
16 . The method of claim 15 , wherein the dsRNA has a 3′ dTdT sequence and a 5′ phosphate group (PO 4 ).
17 . The method of claim 15 , wherein each strand of the dsRNA is encoded by a sequence contained within an expression vector.
18 . The method of claim 12 , wherein the at least one siRNA comprises two different siRNA to two different target genes.
19 . The method of claim 12 , wherein the at least one siRNA comprises three different siRNA to three different target genes.
20 - 38 . (canceled)