Means for inhibiting the expression of orc-1

Abstract

The present invention is related to a nucleic acid molecule comprising a double-stranded structure, whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and said first stretch is at least partially complementary to a target nucleic acid, and whereby the second strand comprises a second stretch of contiguous nucleotides and said second stretch is at least partially complementary to the first stretch, whereby the first stretch comprises a nucleic acid sequence which is at least complementary to a nucleotide core sequence of the nucleic acid sequence according to SEQ ID NO: 1, whereby the nucleotide core sequence comprises the nucleotide sequence from nucleotide positions 1755 to 1763 of SEQ ID NO: 1; from nucleotide positions 1904 to 1912 of SEQ ID NO: 1; from nucleotide positions 1905 to 1913 of SEQ ID NO: 1; from nucleotide positions 2548 to 2556 of SEQ ID NO: 1; whereby the first stretch is additionally at least partially complementary to a region preceding the 5′ end of the nucleotide core sequence and/or to a region following the 3′ end of the nucleotide core sequence.

1 . A nucleic acid molecule comprising a double-stranded structure that is optionally covalently linked,
 wherein the double-stranded structure comprises a first strand and a second strand,   wherein the first strand comprises a first stretch of contiguous nucleotides and said first stretch is at least partially complementary to a target nucleic acid, and   wherein the second strand comprises a second stretch of contiguous nucleotides and said second stretch is at least partially complementary to the first stretch,   wherein the first stretch comprises a nucleic acid sequence which is at least complementary to a nucleotide core sequence of the nucleic acid sequence according to SEQ ID NO: 1,   wherein the nucleotide core sequence comprises the nucleotide sequence
 from nucleotide positions 1755 to 1763 of SEQ ID NO: 1; 
 from nucleotide positions 1905 to 1913 of SEQ ID NO: 1; or 
 from nucleotide positions 2548 to 2556 of SEQ ID NO: 1; 
   
       wherein the first stretch is additionally at least partially complementary to a region preceding the 5′ end of the nucleotide core sequence and/or to a region following the 3′ end of the nucleotide core sequence. 
     
     
         2 . The nucleic acid according to  claim 1 , wherein the first stretch is complementary to the nucleotide core sequence. 
     
     
         3 . The nucleic acid according to  claim 1 , wherein the first stretch is additionally complementary to the region following the 3′ end of the nucleotide core sequence. 
     
     
         4 . The nucleic acid according to  claim 1 , wherein the first stretch is complementary to the target nucleic acid over: a) 18 to 29 nucleotides, b) 19 to 25 nucleotides; or c) 19 to 23 nucleotides. 
     
     
         5 . The nucleic acid according to  claim 4 , wherein the nucleotides are consecutive nucleotides. 
     
     
         6 . The nucleic acid according to  claim 1 , wherein the first stretch and/or the second stretch comprises: a) 18 to 29 consecutive nucleotides, b) 19 to 25 consecutive nucleotides or c) 19 to 23 consecutive nucleotides. 
     
     
         7 . The nucleic acid according to  claim 1 , wherein the first strand consists of the first stretch and/or the second strand consists of the second stretch. 
     
     
         8 . The nucleic acid according to  claim 1 , wherein the double-stranded structure is formed by a first strand and a second one strand, the first strand comprises a first stretch of contiguous nucleotides and the second strand comprises a second stretch of contiguous nucleotides and said first stretch is at least partially complementary to said second stretch, wherein:
 the first stretch consists of a nucleotide sequence according to SEQ ID NOs: 2, 22, 24 or 26, and the second stretch consists of a nucleotide sequence according to SEQ ID NOs: 3, 23, 25 or 27;   the first stretch consists of a nucleotide sequence according to SEQ ID NOs: 8, 38, 40 or 42, and the second stretch consists of a nucleotide sequence according to SEQ ID NOs: 9, 39, 41 or 43;   the first stretch consists of a nucleotide sequence according to SEQ ID NOs: 12, 50, 52 or 54, and the second stretch consists of a nucleotide sequence according to SEQ ID NOs: 13, 51, 53 or 55; or   the first stretch consists of a nucleotide sequence according to SEQ ID NOs: 14, 56, 58, 60, and the second stretch consists of a nucleotide sequence according to SEQ ID NOs: 15, 57, 59 or 61.   
     
     
         9 . The nucleic acid according to  claim 1 , wherein the first stretch and/or the second stretch comprises a plurality of groups of modified nucleotides having a modification at the 2′ position, wherein within the stretch each group of modified nucleotides is flanked on one or both sides by a flanking group of nucleotides, wherein the flanking nucleotide(s) forming the flanking group of nucleotides is/are either an unmodified nucleotide or a nucleotide having a modification different from the modification of the modified nucleotides, wherein the first stretch and/or the second stretch comprises at least two groups of modified nucleotides and at least two flanking groups of nucleotides. 
     
     
         10 . The nucleic acid according to  claim 1 , wherein the first stretch and/or the second stretch comprises a pattern of groups of modified nucleotides and/or a pattern of flanking groups of nucleotides, wherein the pattern is a positional pattern. 
     
     
         11 . The nucleic acid according to  claim 1 , wherein the first stretch and/or the second stretch comprise at the 3′ end a dinucleotide. 
     
     
         12 . The nucleic acid according to  claim 1 , wherein the first and/or the second stretch comprise an overhang of 1 to 5 nucleotides at the 3′ end. 
     
     
         13 . The nucleic acid according to  claim 1 , wherein the length of the double-stranded structure is from about 16 to 27 nucleotide pairs. 
     
     
         14 . A lipoplex comprising a nucleic acid according to  claim 1  and a liposome. 
     
     
         15 . The lipoplex according to  claim 14 , wherein the liposome consists of:
 a) about 50 mol % β-arginyl-2,3-diaminopropionic acid-N-palmityl-N-oleyl-amide trihydrochloride;   b) about 48 to 49 mol % 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE); and   c) about 1 to 2 mol % 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene-glycole.   
     
     
         16 . A vector, comprising or coding for a nucleic acid according to  claim 1 . 
     
     
         17 . An isolated cell comprising a nucleic acid according to  claim 1 . 
     
     
         18 . A composition, comprising a nucleic acid according to  claim 1 . 
     
     
         19 . The composition according to  claim 18 , wherein the composition is a pharmaceutical composition optionally further comprising a pharmaceutically acceptable vehicle. 
     
     
         20 . A method of treating a proliferative or DNA virus viral disease comprising the administration of a composition according to  claim 18  to a subject having a proliferative or DNA virus viral disease, wherein said proliferative disease is selected from carcinomas, sarcomas, hematopoietic malignancies, germ cell tumors, bladder cancer, melanoma, breast cancer, non-Hodgkin lymphoma, colon cancer, rectal cancer, pancreatic cancer, endometrial cancer, prostate cancer, kidney cancer, renal cell cancer, non-melanoma skin cancer, leukemia, thyroid cancer, lung cancer, neurofibromatosis or vascular proliferative diseases and wherein the viral disease is selected from Bell palsy, Burkitt lymphoma, chickenpox, cytomegalovirus infections, ecthyma, contagious, encephalitis, herpes simplex, Epstein-Barr virus infections, erythema infectiosum, exanthema subitum, herpes labialis, herpes simplex, herpes zoster, herpes zoster oticus, infectious mononucleosis, molluscum contagiosum, polyomavirus infections, smallpox, warts, infectious mononucleosis or EBV-associated malignancies.