Endothelial cell genes and uses thereof
AssigneesPresident and Fellows of Harvard College, The Brigham and Women's Hospital, Inc.
InventorsUlrich H. von Andrian, Aude Thiriot, Omid Farokhzad, Jinjun Shi
Life of this patent
Estimating the term…
Abstract
Disclosed herein are genes which are differentially expressed in venule endothelial cells (V-ECs) compared to non-venule endothelial cells (NV-ECs) and methods, compositions, kits, and agents relating to those genes.
Claims41
A method of modulating the venuleness of an endothelial cell, comprising contacting the endothelial cell with an effective amount of an agent that modulates expression of at least one gene that is differentially expressed in venule endothelial cells compared to non-venule endothelial cells.
-7. (canceled)
-13. (canceled)
-53. (canceled)
-56. (canceled)
-65. (canceled)
-171. (canceled)
A method of targeting an agent to microvessel endothelial cells in a subject, comprising administering to the subject a therapeutically effective amount of an agent to be targeted to microvessel endothelial cells, wherein the agent is coupled to a microvessel endothelial cell targeting agent.
-204. (canceled)
-226. (canceled)
-309. (canceled)
A method of identifying a candidate agent that modulates the venuleness of an endothelial cell, comprising:
- (a) contacting an endothelial cell or a population of endothelial cells with a test agent;
- (b) detecting expression levels in the endothelial cell or the population of endothelial cells, in the presence of the test agent, of at least one gene which is differentially expressed in venule endothelial cells compared to non-venule endothelial cells;
- and
- (c) identifying a candidate agent that modulates the venuleness of an endothelial cell, wherein:
- (i) the test agent is a candidate agent that induces endothelial cells to become venule endothelial cells if, in the presence of the test agent, the endothelial cell or the population of endothelial cells exhibit elevated levels of expression of at least one gene exhibiting higher expression levels in venule endothelial cells compared to non-venule endothelial cells;
- (ii) the test agent is a candidate agent that induces endothelial cells to become venule endothelial cells if, in the presence of the test agent, the endothelial cell or the population of endothelial cells exhibit reduced levels of expression of at least one gene exhibiting lower expression levels in venule endothelial cells compared to non-venule endothelial cells;
- (iii) the test agent is a candidate agent that induces endothelial cells to become non-venule endothelial cells if, in the presence of the test agent, the endothelial cell or the population of endothelial cells exhibit elevated levels of expression of at least one gene exhibiting higher expression levels in non-venule endothelial cells compared to venule endothelial cells;
- or
- (iv) the test agent is a candidate agent that induces endothelial cells to become non-venule endothelial cells if, in the presence of the test agent, the endothelial cell or the population of endothelial cells exhibit reduced levels of expression of at least one gene exhibiting lower expression levels in non-venule endothelial cells compared to venule endothelial cells.
-314. (canceled)
-330. (canceled)
-349. (canceled)
-355. (canceled)
-359. (canceled)
-382. (canceled)
A method of modulating leukocyte trafficking and/or inflammation in a subject in need thereof, comprising:
- (a) administering to the subject an effective amount of an agent that modulates expression of at least one gene which is differentially expressed in venule endothelial cells compared to non-venule endothelial cells, and (b) modulating leukocyte trafficking and/or inflammation in the subject, wherein:
- (i) an agent that decreases expression of at least one gene which exhibits higher expression levels in venule endothelial cells compared to non-venule endothelial cells inhibits leukocyte trafficking and/or inflammation in the subject;
- (ii) an agent that increases expression of at least one gene which exhibits lower expression levels in venule endothelial cells compared to non-venule endothelial cells inhibits leukocyte trafficking and/or inflammation in the subject;
- (iii) an agent that decreases expression of at least one gene which exhibits higher expression levels in non-venule endothelial cells compared to venule endothelial cells enables leukocyte trafficking and/or inflammation to be induced in the subject;
- or (iv) an agent that increases expression of at least one gene which exhibits lower expression levels in non-venule endothelial cells compared to venule endothelial cells enables leukocyte trafficking and/or inflammation to be induced in the subject.
-387. (canceled)
-403. (canceled)
-832. (canceled)
Dependencies are inferred from the claim text.