VASCULAR THERAPEUTICS
The present invention provides a method of preventing or reducing restenosis, neointima formation, graft failure, atherosclerosis, angiogenesis and/or solid tumour growth in a subject. The method comprises administering to the subject a prophylactically effective dose of a nucleic acid which decreases the level of c-Jun mRNA, c-Jun mRNA translation or nuclear accumulation or activity of c-Jun. It is preferred that the nucleic acid is a DNAzyme that targets c-Jun mRNA.
1 - 2 . (canceled)
3 . A method of treating or inhibiting solid tumor growth in a subject, the method comprising administering to a subject an effective dose of a a DNAzyme targeted against c-Jun, wherein the DNAzyme comprises:
(i) a catalytic domain which cleaves mRNA at a purine:pyrimidine cleavage site;
(ii) first binding domain contiguous with the 5′ end of the catalytic domain; and
(iii) a second binding domain contiguous with the 3′ end of the catalytic domain; wherein the binding domains are sufficiently complementary to two regions immediately flanking a purine:pyrimidine cleavage site within the c-Jun mRNA such that the DNAzyme cleaves the c-Jun mRNA.
4 . (canceled)
5 . The method according to claim 3 , wherein the solid tumor growth is melanoma.
6 - 10 . (canceled)
11 . The method according to claim 3 , wherein both binding domains have a combined total length of at least 14 nucleotides.
12 . The method according to claim 3 , wherein the binding domain lengths are 9 nucleotides.
13 . The method according to claim 3 , wherein the catalytic domain has a nucleotide sequence GGCTAGCTACAACGA.
14 . (canceled)
15 . The method according to claim 3 , wherein the DNAzyme cleaves c-Jun mRNA in the region from residues U1296 to G1497.
16 . The method according to claim 3 , wherein the cleavage site is the GU site corresponding to nucleotides 1311-1312 of SEQ ID NO:1.
17 . (canceled)
18 . The method according to claim 3 , wherein the DNAzyme incorporates a 3′-3′ inversion at one or more termini.
19 - 40 . (canceled)
41 . A method of treating or inhibiting solid tumor growth in a subject, the method comprising administering to the subject an effective dose of a DNAzyme targeted against c-Jun, wherein the DNAzyme has the sequence of SEQ ID NO:5.
42 . The method according to claim 41 , wherein the solid tumor growth is melanoma.
43 . The method according to claim 41 , wherein the DNAzyme incorporates a 3′-3′ inversion at one or more termini.