COMPOSITIONS AND METHODS FOR DELIVERING POLYNUCLEOTIDES
The disclosure relates to compositions, methods, and kits for using perillyl alcohol and/or an Argonaute protein (e.g., Ago-2) to deliver a polynucleotide to a cell. The disclosure also relates to compositions, methods, and kits for treating a condition by using perillyl alcohol and/or an Argonaute protein (e.g., Ago-2) to deliver a polynucleotide to a cell. The conditions may be brain vascular diseases and brain tumors.
1 . A method of delivering a polynucleotide to a cell, the method comprising:
contacting the cell with the polynucleotide and perillyl alcohol (POH).
2 . The method of claim 1 , wherein the polynucleotide and POH are provided in one composition.
3 . The method of claim 1 , wherein the polynucleotide and POH are provided in separate compositions.
4 . The method of claim 1 , wherein the polynucleotide and POH are mixed prior to contacting the cell.
5 . The method of claim 1 , wherein the polynucleotide is a microRNA (miRNA).
6 . The method of claim 5 , wherein the miRNA is miR-18a.
7 . The method of claim 1 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
8 . A method of delivering a polynucleotide to a cell, the method comprising:
contacting the cell with the polynucleotide, perillyl alcohol (POH) and an Argonaute protein or a variant thereof.
9 . The method of claim 8 , wherein the Argonaute protein is Argonaute-2 (Ago-2).
10 . The method of claim 8 , wherein the polynucleotide, POH and the Argonaute protein or a variant thereof are provided in one composition.
11 . The method of claim 8 , wherein the polynucleotide, POH and the Argonaute protein or a variant thereof are provided in two or three compositions.
12 . The method of claim 8 , wherein the polynucleotide, POH and the Argonaute protein or a variant thereof are mixed prior to contacting the cell.
13 . The method of claim 8 , wherein the polynucleotide is a microRNA (miRNA).
14 . The method of claim 13 , wherein the miRNA is miR-18a.
15 . The method of claim 8 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
16 . A method of delivering a polynucleotide to a subject, the method comprising administering the polynucleotide, perillyl alcohol (POH), and optionally an Argonaute protein or a variant thereof to the subject.
17 . The method of claim 16 , wherein the Argonaute protein is Argonaute-2 (Ago-2).
18 . The method of claim 16 , wherein the polynucleotide is a microRNA (miRNA).
19 . The method of claim 16 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
20 . The method of claim 19 , wherein the miRNA is miR-18a.
21 . The method of claim 16 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are provided in one composition.
22 . The method of claim 16 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are provided in two or three compositions.
23 . The method of claim 16 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are mixed prior to administration to the subject.
24 . A method of treating a condition in a subject, the method comprising of administering a polynucleotide, perillyl alcohol (POH), and optionally an Argonaute protein or a variant thereof to the subject.
25 . The method of claim 24 , wherein the polynucleotide is a microRNA (miRNA).
26 . The method of claim 25 , wherein the miRNA is miR-18a.
27 . The method of claim 24 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
28 . The method of claim 24 , wherein the Argonaute protein is Argonaute-2 (Ago-2).
29 . The method of claim 24 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are provided in one composition.
30 . The method of claim 24 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are provided in separate compositions.
31 . The method of claim 24 , wherein the polynucleotide, POH and optionally the Argonaute protein or a variant thereof are mixed prior to administration to the subject.
32 . The method of claim 24 , wherein the condition is a neurovascular disease.
33 . The method of claim 24 , wherein the condition is a stroke.
34 . The method of claim 24 , wherein the condition is a tumor.
35 . The method of claim 24 , wherein the condition is a brain tumor, glioma, glioblastoma, and/or glioblastoma multiforme (GBM).
36 . The method of claim 24 , wherein the condition is a spinal cord injury.
37 . The method of claim 24 , wherein the administration is intranasal, intratumoral, intracranial, intraventricular, intrathecal, epidural, intradural, intravascular, intravenous, intraarterial, intramuscular, subcutaneous, intraperitoneal, or oral.
38 . The method of claim 24 , wherein the administration is given once, twice, three or more times.
39 . The method of claim 24 , further comprising administering an anti-angiogenic drug to the subject.
40 . The method of claim 24 , further comprising administering a chemotherapeutic agent to the subject.
41 . A kit comprising: (i) a polynucleotide; (ii) perillyl alcohol (POH); and
(iii) instructions for delivering the polynucleotide to a cell or a subject using POH.
42 . The kit of claim 41 , wherein the polynucleotide is a microRNA (miRNA).
43 . The kit of claim 42 , wherein the miRNA is miR-18a.
44 . The kit of claim 41 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
45 . A kit comprising: (i) a polynucleotide; (ii) perillyl alcohol (POH); (iii) an Argonaute protein or a variant thereof; and (iv) instructions for delivering the polynucleotide to a cell or a subject using the POH and the Argonaute protein or a variant thereof.
46 . The kit of claim 45 , wherein the polynucleotide is a microRNA (miRNA).
47 . The kit of claim 46 , wherein the miRNA is miR-18a.
48 . The kit of claim 45 , wherein the polynucleotide is a short interfering RNA (siRNA) or a short-hairpin RNA (shRNA).
49 . The kit of claim 45 , wherein the Argonaute protein is Argonaute-2 (Ago-2).