US2015190532A1PendingUtilityA1
Smooth muscle specific inhibition for anti-restenotic therapy
Est. expiryApr 4, 2032(~5.7 yrs left)· nominal 20-yr term from priority
A61K 48/005A61K 48/0058C12N 15/86C12N 2710/10043C12N 2830/008C12N 15/111C12N 2320/30C12N 2310/141C12N 2799/022
56
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Claims
Abstract
The present invention provides for the incorporation of target sequences of microRNAs into the 3′ UTR region of a gene of interest in nucleic acid vectors. The invention also provides for an expression system comprising such vectors, a pharmaceutical composition comprising such vectors, as well as methods of treating or preventing cardiovascular disease by using such vectors.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A nucleic acid vector comprising a gene of interest, and one or more target sequences for a microRNA within the 3′ UTR region of the gene of interest.
2 . The nucleic acid vector of claim 1 , wherein the gene of interest is the p27 gene.
3 . The nucleic acid vector of claim 1 , wherein the microRNA is miR-126.
4 . The nucleic acid vector of claim 3 , wherein the one or more target sequences comprise SEQ ID NO:2.
5 . The nucleic acid vector of claim 1 , wherein the vector comprises four target sequences for a microRNA.
6 . The nucleic acid vector of claim 5 , wherein the target sequences for a microRNA are identical.
7 . The nucleic acid vector of claim 6 , wherein the target sequences for a microRNA comprise SEQ ID NO:2.
8 . The nucleic acid vector of claim 1 , wherein the vector comprises a second gene of interest.
9 . The nucleic acid vector of claim 8 , wherein the vector comprises one or more target sequences for a microRNA within the 3′ UTR region of the second gene of interest.
10 . The nucleic acid vector of claim 1 , wherein the nucleic acid vector is a viral vector.
11 . The nucleic acid vector of claim 10 , wherein the viral vector is an adenoviral vector.
12 . The nucleic acid vector of claim 1 , wherein the vector is delivered to a cell of interest.
13 . The nucleic acid vector of claim 12 , wherein the cell of interest is an endothelial cell.
14 . An expression system comprising a nucleic acid vector, wherein the nucleic acid vector comprises a gene of interest, and one or more target sequences for a microRNA within the 3′ UTR region of the gene of interest.
15 . The expression system of claim 14 , wherein the gene of interest is the p27 gene.
16 . The expression system of claim 14 , wherein the microRNA is miR-126.
17 . The expression system of claim 16 , wherein the one or more target sequences comprise SEQ ID NO:2.
18 . The expression system of claim 14 , wherein the vector comprises four target sequences for a microRNA.
19 . The expression system of claim 18 , wherein the target sequences for a microRNA are identical.
20 . The expression system of claim 19 , wherein the target sequences for a microRNA comprise SEQ ID NO:2.
21 . The expression system of claim 14 , wherein the vector comprises a second gene of interest.
22 . The expression system of claim 21 , wherein the vector comprises one or more target sequences for a microRNA within the 3′ UTR region of the second gene of interest.
23 . The expression system of claim 14 , wherein the nucleic acid vector is a viral vector.
24 . The expression system of claim 23 , wherein the viral vector is an adenoviral vector.
25 . A cell comprising a nucleic acid vector, wherein the nucleic acid vector comprises a gene of interest, and one or more target sequences for a microRNA within the 3′ UTR region of the gene of interest.
26 . The cell of claim 25 , wherein the gene of interest is the p27 gene.
27 . The cell of claim 25 , wherein the microRNA is miR-126.
28 . The cell of claim 27 , wherein the one or more target sequences comprise SEQ ID NO:2.
29 . The cell of claim 25 , wherein the vector comprises four target sequences for a microRNA.
30 . The cell of claim 29 , wherein the target sequences for a microRNA are identical.
31 . The cell of claim 30 , wherein the target sequences for a microRNA comprise SEQ ID NO:2.
32 . The cell of claim 25 , wherein the vector comprises a second gene of interest.
33 . The cell of claim 32 , wherein the vector comprises one or more target sequences for a microRNA within the 3′ UTR region of the second gene of interest.
34 . The cell of claim 25 , wherein the nucleic acid vector is a viral vector.
35 . The cell of claim 34 , wherein the viral vector is an adenoviral vector.
36 . The cell of claim 25 , wherein the cell is an endothelial cell.
37 . The cell of claim 25 , wherein the cell is a vascular smooth muscle cell.
38 . A pharmaceutical composition comprising a nucleic acid vector, wherein the nucleic acid vector comprises a gene of interest, and one or more target sequences for a microRNA within the 3′ UTR region of the gene of interest.
39 . The pharmaceutical composition of claim 38 , wherein the gene of interest is the p27 gene.
40 . The pharmaceutical composition of claim 38 , wherein the microRNA is miR-126.
41 . The pharmaceutical composition of claim 40 , wherein the one or more target sequences comprise SEQ ID NO:2.
42 . The pharmaceutical composition of claim 41 , wherein the vector comprises four target sequences for a microRNA.
43 . The pharmaceutical composition of claim 42 , wherein the target sequences for a microRNA are identical.
44 . The pharmaceutical composition of claim 43 , wherein the target sequences for a microRNA comprise SEQ ID NO:2.
45 . The pharmaceutical composition of claim 38 , wherein the vector comprises a second gene of interest.
46 . The pharmaceutical composition of claim 45 , wherein the vector comprises one or more target sequences for a microRNA within the 3′ UTR region of the second gene of interest.
47 . The pharmaceutical composition of claim 38 , wherein the nucleic acid vector is a viral vector.
48 . The pharmaceutical composition of claim 47 , wherein the viral vector is an adenoviral vector.
49 . A method of treating or preventing a cardiovascular disease in a subject in need thereof, the method comprising administering a nucleic acid vector to the subject, wherein the nucleic acid vector comprises a gene of interest and one or more target sequences for a microRNA within the 3′ UTR region of the gene of interest.
50 . The method of claim 49 , wherein the gene of interest is the p27 gene.
51 . The method of claim 49 , wherein the microRNA is miR-126.
52 . The method of claim 51 , wherein the one or more target sequences comprise SEQ ID NO:2.
53 . The method of claim 52 , wherein the vector comprises four target sequences for a microRNA.
54 . The method of claim 53 , wherein the target sequences for a microRNA are identical.
55 . The method of claim 54 , wherein the target sequences for a microRNA comprise SEQ ID NO:2.
56 . The method of claim 49 , wherein the vector comprises a second gene of interest.
57 . The method of claim 56 , wherein the vector comprises one or more target sequences for a microRNA within the 3′ UTR region of the second gene of interest.
58 . The method of claim 49 , wherein the nucleic acid vector is a viral vector.
59 . The method of claim 58 , wherein the viral vector is an adenoviral vector.
60 . The method of claim 49 , wherein the nucleic acid vector is delivered into a cell of the subject.
61 . The method of claim 60 , wherein the cell expresses the microRNA.
62 . The method of claim 60 , wherein the gene of interest is not expressed in the cell.
63 . The method of claim 60 , wherein the cell is an endothelial cell.
64 . The method of claim 60 , wherein the cell is a vascular smooth muscle cell.
65 . The method of claim 60 , wherein the cardiovascular disease is coronary artery disease.Join the waitlist — get patent alerts
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