Compositions and methods related to mirna modulation of neovascularization or angiogenesis

Abstract

The present invention concerns methods and compositions for diagnosing and/or treating vascular diseases including cancer, cardiac diseases, vascular diseases of the eye, and inflammatory diseases. The methods involve measuring the levels of one or multiple miRNAs in patient samples and using the test results to diagnose and/or predict an optimal treatment regimen for the patient. Compositions described in the invention include nucleic acids that function as miRNAs or miRNA inhibitors that can be introduced to a patient to reduce or increase vascularization as needed.

1 . A method for reducing vascularization in a subject or tissue comprising administering to the subject or tissue in need of such a reduction, in an amount sufficient to reduce vascularization, one or more nucleic acid molecule comprising:
 (a) a nucleic acid sequence that is at least 80% identical to one or more of miR-184, miR-150, miR-409, miR-375, miR-129-5p, miR-142a, miR-29a, miR-129-3p, miR-10b, miR-96, miR-183, miR-16, miR-182, miR-191, miR-29c, miR-181c, miR-335, miR-7026, miR-210, miR-512-3p, miR-132, miR-500, miR-339, miR-511, miR-26b, miR-30b, or miR-15a, or complement thereof; and/or   (b) an inhibitor of miR-451, miR-424, miR-146, miR-214, miR-199a, miR-181, miR-350, miR-21, miR-218, miR-148b, miR-106a, miR-205, miR-365, miR-299-5p, ambi-miR-7079, miR-200a, miR-351, miR-329, miR-122a, miR-20a, miR-520h, miR-142-5p, miR-203, miR-211, miR-145, let-7b, miR-93, miR-192, miR-201, miR-18a, miR-17-5p, miR-7085, miR-106b, or miR-223.   
     
     
         2 .- 15 . (canceled) 
     
     
         16 . A method of stimulating vascularization in subject or tissue comprising administering to a subject in need of such stimulation, in an amount sufficient to stimulate vascularization, one or more nucleic acid molecule comprising
 (a) a miRNA sequence that is at least 80% identical to one or more of miR-451, miR-424, miR-146, miR-214, miR-199a, miR-181, miR-350, miR-21, miR-218, miR-148b, miR-106a, miR-205, miR-365, miR-299-5p, ambi-miR-7079, miR-200a, miR-351, miR-329, miR-122a, miR-20a, miR-520h, miR-142-5p, miR-203, miR-211, miR-145, let-7b, miR-93, miR-192, miR-201, miR-18a, miR-17-5p, miR-7085, miR-106b, and/or miR-223; and/or   (b) an inhibitor of miR-184, miR-31, miR-150, miR-409, miR-375, miR-129-5p, miR-142a, miR-29a, miR-129-3p, miR-10b, miR-96, miR-183, miR-16, miR-182, miR-191, miR-29c, miR-181c, miR-335, miR-7026, miR-210, miR-512-3p, miR-132, miR-500, miR-339, miR-511, miR-26b, miR-30b, and/or miR-15a.   
     
     
         17 . The method of  claim 16 , wherein the nucleic acid is administered topically, enterally, parenterally or intravitreally. 
     
     
         18 . The method of  claim 16  wherein the subject has, is at risk of developing, or is suspected of having coronary artery disease (CAD), cardiac failure, tissue injury, or ischemia. 
     
     
         19 .- 20 . (canceled) 
     
     
         21 . A method for evaluating a patient comprising the steps of:
 (a) determining expression levels of one or more of miR-451, miR-424, miR-146, miR-214, miR-199a, miR-181, miR-350, miR-21, miR-218, miR-148b, miR-106a, miR-205, miR-365, miR-299-5p, ambi-miR-7079, miR-200a, miR-351, miR-329, miR-122a, miR-20a, miR-520h, miR-142-5p, miR-203, miR-211, miR-145, let-7b, miR-93, miR-192, miR-201, miR-18a, miR-17-5p, miR-7085, miR-106b, miR-223, miR-184, miR-31, miR-150, miR-409, miR-375, miR-129-5p, miR-142a, miR-29a, miR-129-3p, miR-10b, miR-96, miR-183, miR-16, miR-182, miR-191, miR-29c, miR-181c, miR-335, miR-7026, miR-210, miR-512-3p, miR-132, miR-500, miR-339, miR-511, miR-26b, miR-30b, and/or miR-15a in a biological sample comprising a portion of a tissue or fluid associated with a condition associated with aberrant vacularization , and   (b) determining a diagnosis or prognosis for the aberrant vascularization condition based on the miRNA expression levels.   
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 21 , wherein determining a diagnosis is screening for a pathological condition, staging a pathological condition, or assessing response of a pathological condition to therapy. 
     
     
         24 . The method of  claim 23 , wherein determining a diagnosis is determining if the patient has a condition associated with aberrant neovascularization or aberrant angiogenesis. 
     
     
         25 . The method of  claim 21 , further comprising normalizing the expression levels of miRNA. 
     
     
         26 .- 29 . (canceled) 
     
     
         30 . The method of  claim 21 , wherein expression of the miRNA is determined by an amplification assay or a hybridization assay. 
     
     
         31 .- 32 . (canceled) 
     
     
         33 . The method of  claim 30 , wherein the hybridization assay is an array hybridization assay or a solution hybridization assay. 
     
     
         34 . The method of  claim 21 , further comprising providing a report of the diagnosis or prognosis. 
     
     
         35 . The method of  claim 21 , further comprising obtaining a sample from the patient. 
     
     
         36 .- 40 . (canceled) 
     
     
         41 . A kit for analysis of a sample by assessing miRNA profile for a sample comprising, in suitable container means, two or more miRNA hybridization or amplification reagents comprising one or more probe or amplification primer for one or more miRNA selected from miR-451, miR-424, miR-146, miR-214, miR-199a, miR-181, miR-350, miR-21, miR-218, miR-148b, miR-106a, miR-205, miR-365, miR-299-5p, ambi-miR-7079, miR-200a, miR-351, miR-329, miR-122a, miR-20a, miR-520h, miR-142-5p, miR-203, miR-211, miR-145, let-7b, miR-93, miR-192, miR-201, miR-18a, miR-17-5p, miR-7085, miR-106b, miR-223, miR-184, miR-31, miR-150, miR-409, miR-375, miR-129-5p, miR-142a, miR-29a, miR-129-3p, miR-10b, miR-96, miR-183, miR-16, miR-182, miR-191, miR-29c, miR-181c, miR-335, miR-7026, miR-210, miR-512-3p, miR-132, miR-500, miR-339, miR-511, miR-26b, miR-30b, and/or miR-15a. 
     
     
         42 . The kit of  claim 41 , further comprising reagents for detecting an miRNA in the sample. 
     
     
         43 . The kit of  claim 41 , wherein miRNA hybridization reagent comprises hybridization probes. 
     
     
         44 . The kit of  claim 41 , wherein miRNA amplification reagent comprises one or more of amplification primers or a probe for the detection of an miRNA sequence.