Use of double-stranded ribonucleic acid for inducing cell lysis
The present invention is related to the use of a ribonucleic acid for the manufacture of a medicament, wherein the ribonucleic acid comprises a double-stranded structure and the double-stranded structure comprises a first and a second strand, wherein the first strand comprises a first stretch of contiguous nucleotides and the second strand comprises a second stretch of contiguous nucleotides, wherein the first stretch is not complementary to a nucleic acid, preferably a mRNA, of a cell of an organism to be treated with said medicament and/or wherein the second stretch is different from a nucleic acid, preferably a mRNA of a cell of an organism to be treated with said medicament.
1 . A pharmaceutical composition comprising a nucleic acid, wherein the nucleic acid comprises a double-stranded structure and the double-stranded structure comprises a first strand and a second strand,
wherein the first strand comprises a first stretch of contiguous nucleotides and the second strand comprises a second stretch of contiguous nucleotides,
wherein the first stretch is not complementary to a target nucleic acid of a cell of an organism to be treated with said medicament and/or
wherein the second stretch is different from a target nucleic acid of a cell of an organism to be treated with said medicament;
and a pharmaceutically acceptable carrier.
2 . The composition according to claim 1 , wherein said nucleic acid is a ribonucleic acid.
3 . The pharmaceutical composition according to claim 1 , wherein said target nucleic acid is any nucleic acid of a cell of an organism to be treated using said pharmaceutical composition.
4 . The composition according to claim 3 , wherein said target nucleic acid in said cell is an mRNA.
5 . The composition according to claim 1 , wherein said target nucleic acid is an element of the transcriptome of a cell of an organism to be treated with said pharmaceutical composition.
6 . The composition according to claim 5 , wherein said target nucleic acid is, all elements of the transcriptome of said organism.
7 . The composition according to claim 1 , wherein said cell is a pathological cell which is associated with the disease which is to be treated and/or prevented by the pharmaceutical composition.
8 . The composition according to claim 1 , further comprising at least one lipid.
9 . The composition according to claim 8 , wherein said lipid is a cationic lipid.
10 . The composition according to claim 9 , wherein said lipid is beta-arginyl-2,3-diaminopropionic acid-N-palmityl-N-oleyl-amide trihydrochloride.
11 . The composition according to claim 8 , further comprising a helper lipid.
12 . The composition according to claim 11 , wherein said helper lipid is diphytanoylphosphatidylethanolamine.
13 . A method for the treatment of a disease in a subject, comprising administering to a subject suffering from said disease an effective amount of a composition according to claim 1 , wherein said cell of an organism is a cell of said subject.
14 . The method according to claim 13 , wherein said disease is cancer.
15 . A method of treating a disease in a subject, comprising administering to a subject suffering from said disease an effective amount of a nucleic acid, wherein said nucleic acid comprises a double-stranded structure and the double-stranded structure comprises a first and a second strand,
wherein said first strand comprises a first stretch of contiguous nucleotides and the second strand comprises a second stretch of contiguous nucleotides,
wherein said first stretch is not complementary to a target nucleic acid of a cell of said subject to be treated with said nucleic acid and/or
wherein said second stretch is different from a target nucleic acid of a cell of said subject to be treated with said nucleic acid.
16 . The method according to claim 15 , wherein said nucleic acid is a ribonucleic acid.
17 . The method according to claim 15 , wherein said target nucleic acid is an RNA
18 . The method according to claim 17 , wherein said target nucleic acid is any or all elements of the transcriptome of a cell of an organism.
19 . The method according to claim 15 , wherein said cell of said subject is a pathological cell involved in said disease.
20 . The method according to claim 15 , wherein said first stretch is complementary to a nucleic acid of a non-pathological cell of said subject and/or
wherein the second stretch is identical to a target nucleic acid of a non-pathological cell of said subject.
21 . The method according to claim 20 , wherein said nucleic acid is an mRNA.
22 . The method according to claim 21 , wherein the target nucleic acid of the non-pathological cell differs from the target nucleic acid of the pathological cell at one or more nucleotide positions.
23 . The method according to claim 15 , wherein said disease is a tumor or cancer.
24 . The method according to claim 19 , wherein said pathological cell is tumor suppressor-defective and said first stretch of contiguous nucleotides is complementary to the nucleic acid coding for the functional tumor suppressor and/or
said second stretch of contiguous nucleotides is identical to the nucleic acid coding for the functional tumor suppressor.
25 . The method according to claim 24 , wherein said first stretch is complementary to the nucleic acid coding for the functional tumor suppressor for which the pathological cell is tumor suppressor-defective, and
the second stretch is identical to the nucleic acid coding for the functional tumor suppressor for which the pathological cell is tumor suppressor-defective.
26 . The method according to claim 19 , wherein the pathological cell is lacking a gene of the functional tumor suppressor or a transcript thereof.
27 . The method according to claim 19 , wherein the pathological cell is lacking a gene or a transcript thereof providing for a functionally active tumor suppressor
28 . The method according to claim 27 , wherein the gene or the transcript thereof comprises one or several mutations, wherein each mutation is selected from the group consisting of point mutations and deletion mutations, wherein said mutation(s) results in a functionally inactive tumor suppressor.
29 . The method according to claim 15 , wherein said nucleic acid is RNA interference response-negative.
30 . The method according to claim 29 , wherein said nucleic acid is RNA interference response-negative in pathological cells of the subject.
31 . The method according to claim 29 , wherein said nucleic acid is RNA interference response-positive in non-pathological cells of said subject.
32 . The method according to claim 15 , wherein the nucleic acid induces a stress response in said cells.
33 . The method according to claim 32 , wherein said stress response is apoptosis and/or inhibition of proliferation of the pathological cells.