Therapeutic uses of microvesicles and related micrornas

Patent metadata

Field	Value
Publication number	US-2016243171-A1
Application number	US-201614987931-A
Country	US
Kind code	A1
Filing date	Jan 5, 2016
Priority date	Aug 13, 2010
Publication date	Aug 25, 2016
Grant date	—

Abstract

The present invention provides improved methods and compositions based on microvesicles for the treatment of various diseases, disorders and conditions. In particular, the present invention encompasses the recognition that microvesicles contain specific microRNAs which may function as intercellular regulators involved in cell or tissue regeneration, remodeling, reconstruction, reprogramming or transdifferentiation. Thus, among other things, the present invention provides methods and compositions based on microvesicles and/or associated microRNAs that provide more predictable and effective therapeutic results.

First claim

What is claimed is:

1 . A composition comprising purified microvesicles isolated from cells originated from kidney, liver, spleen, lymph node, myometrium, peripheral blood, cord blood, bone marrow, serum, mesenchymal tissue, or a combination thereof.

2 .- 3 . (canceled)

4 . The composition of claim 1 , wherein the cells are mammalian.

5 . The composition of claim 4 , wherein the mammalian cells are rat.

6 . The composition of claim 4 , wherein the mammalian cells are human.

7 . The composition of claim 1 , wherein the microvesicles comprise one or more miRNA selected from the group consisting of miRNA-122 (SEQ ID NO: 2), miRNA-127 (SEQ ID NO: 5), miRNA-133b (SEQ ID NO: 7), miRNA-323 (SEQ ID NO: 10), miRNA-346 (SEQ ID NO: 13), miRNA-433 (SEQ ID NO: 15), miRNA-451 (SEQ ID NO: 17), miRNA-466h (SEQ ID NO: 18), miRNA-467c (SEQ ID NO: 19), miRNA-467e (SEQ ID NO: 20), miRNA-468 (SEQ ID NO: 22), miRNA-491-5p (SEQ ID NO: 23), miRNA-491-3p (SEQ ID NO: 24), miRNA-495 (SEQ ID NO: 26), miRNA-546 (SEQ ID NO: 27), miRNA-666 (SEQ ID NO: 28), miRNA-680 (SEQ ID NO: 29), miRNA-136 (SEQ ID NO: 30), miRNA-202 (SEQ ID NO: 34), miRNA-206 (SEQ ID NO: 36), miRNA-224 (SEQ ID NO: 39), miRNA-327 (SEQ ID NO: 40), miRNA-347 (SEQ ID NO: 41), miRNA-369-5p (SEQ ID NO: 44), miRNA-369-3p (SEQ ID NO: 45), miRNA-370 (SEQ ID NO: 47), miRNA-375 (SEQ ID NO: 49), miRNA-376b-5p (SEQ ID NO: 51), miRNA-376b-3p (SEQ ID NO: 52), miRNA-381(SEQ ID NO: 54), miRNA-434 (SEQ ID NO: 55), miRNA-452 (SEQ ID NO: 56), miRNA-465a-5p (SEQ ID NO: 58), miRNA-465a-3p (SEQ ID NO: 59), miRNA-465b-5p (SEQ ID NO: 60), miRNA-465b-3p (SEQ ID NO: 61), miRNA-470 (SEQ ID NO: 62), miRNA-487b (SEQ ID NO: 64), miRNA-543 (SEQ ID NO: 66), miRNA-547 (SEQ ID NO: 68), miRNA-590-5p (SEQ ID NO: 69), miRNA-590-3p (SEQ ID NO: 70), miRNA-741 (SEQ ID NO: 71), and miRNA-881 (SEQ ID NO: 72).

8 . The composition of claim 1 wherein the microvesicles comprise one or more miRNA selected from the group consisting of miRNA-122 (SEQ ID NO: 2), miRNA-127 (SEQ ID NO: 5), miRNA-133b (SEQ ID NO: 7), miRNA-323 (SEQ ID NO: 10), miRNA-346 (SEQ ID NO: 13), miRNA-433 (SEQ ID NO: 15), miRNA-451 (SEQ ID NO: 17), miRNA-466h (SEQ ID NO: 18), miRNA-467c (SEQ ID NO: 19), miRNA-467e (SEQ ID NO: 20), miRNA-468 (SEQ ID NO: 22), miRNA-491-5p (SEQ ID NO: 23), miRNA-491-3p (SEQ ID NO:24), miRNA-495 (SEQ ID NO: 26), miRNA-546 (SEQ ID NO: 27), miRNA-666 (SEQ ID NO: 28), and miRNA-680 (SEQ ID NO: 29).

9 . The composition of claim 8 wherein the microvesicles do not contain miRNA-7b (SEQ ID NO: 73), miRNA-17-3p (SEQ ID NO: 74), miRNA-32 (SEQ ID NO: 75), miRNA-34c (SEQ ID NO: 76), miRNA-129-5p (SEQ ID NO: 78), miRNA-190 (SEQ ID NO: 79), miRNA-203 (SEQ ID NO: 80), miRNA-376c (SEQ ID NO: 81), miRNA-381 (SEQ ID NO: 82), miRNA-384-3p (SEQ ID NO: 83), miRNA-455 (SEQ ID NO: 84), miRNA-499 (SEQ ID NO: 85), miRNA-505 (SEQ ID NO: 86), miRNA-582-5p (SEQ ID NO: 87), miRNA-615-3p (SEQ ID NO: 88), and miRNA-615-5p (SEQ ID NO: 89).

10 . The composition of claim 1 , wherein the microvesicles have a mean diameter of from about 100 nm to about 1000 nm.

11 . The composition of claim 1 , wherein the pathfinder cells are cultured under hypoxic conditions.

12 . The composition of claim 1 , wherein the pathfinder cells are cultured in a medium that is substantially free of serum.

13 . The composition of claim 1 , wherein the microvesicles are characterized by an ability to increase the proliferation of cells.

14 . The composition of claim 13 , wherein the microvesicles are characterized by an ability to increase the proliferation of cells in an in vitro culture system.

15 . The composition of claim 14 , wherein the proliferation of cells is measured by doubling time.

16 . The composition of claim 1 , wherein the microvesicles are characterized by an ability to stimulate migration or regrowth of cells.

17 . A method for increasing the proliferation of cells comprising the step of contacting the cells with a composition comprising purified microvesicles isolated from cells originated from pancreas, kidney, or lymph node pancreas, kidney, liver, spleen, lymph node, myometrium, peripheral blood, cord blood, bone marrow, serum, mesenchymal tissue, or a combination thereof.

18 .- 21 . (canceled)

22 . The method of claim 17 , wherein the microvesicles are administered in vivo.

23 . The method of claim 17 , wherein the microvesicles are administered in vitro.

24 . A method of treating a disease, disorder, or condition associated with tissue damage in a subject comprising the step of administering to the subject a composition comprising purified microvesicles isolated from cells originated from pancreas, kidney, liver, spleen, lymph node, myometrium, peripheral blood, cord blood, bone marrow, serum, mesenchymal tissue, or a combination thereof.

25 . (canceled)

26 . The method of claim 24 , wherein the disease, disorder, or condition is selected from the group consisting of diabetes mellitus, congestive myocardial failure, myocardial infarct, acute renal disease, chronic renal disease, and traumatic injury.

27 .- 30 . (canceled)

Assignees

• Univ Glasgow Court

Inventors

• Shiels Paul
• Davies Wayne

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title